Introduction. Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm (MPN) that without therapy is a uniformly lethal disease. Historically allogenic stem cell transplant (HCT) was the only curative therapy. In 2001 imatinib was the first CML specific oral tyrosine kinase inhibitor (TKI) approved and since then the treatment of CML has dramatically improved. Subsequently, 2nd and 3rd generation TKIs were developed and have been shown to be superior to imatinib either as initial therapy in certain high-risk patients and in other patients that fail imatinib. However, despite the advances in therapy, patients still die of CML, in fact, in 2020 it is estimated that 8,450 patients will be diagnosed with CML and 1,130 patients will die of CML. HCT remains a curative option for patients with CML. As the safety and availability of HCT improve, we aimed to describe the role of transplant in the modern era of CML therapy. Methods. We performed a retrospective chart review of patients who underwent their first HCT between June 28, 2006 and December 31, 2021 for CML in either chronic or accelerated phase at the time of transplant. Results. A total of 122 patients were identified. Patient and HCT characteristics are shown in Table 1. The median age at time of transplant was 45 (8-67), 72 (59%) are male. Fifty-four (44.3%) of patients received their transplant between 2006-2012 and 68 (55.7%) of patients received their transplants between 2013-2021. Fourteen (11.5%) patients were in accelerated phase CML at the time of HCT and the rest were in chronic phase. The median time from diagnosis to transplant was 23 months (1.8-307). Ninety-seven patients (79.5%) received ablative conditioning regimens. A total of 46 patients (37.7%) had matched related donors, 54 patients (44.3%) had matched unrelated donors, 14 patients (11.5%) had haploidentical donors, and 8 patients (6.7%) had a cord blood graft. 102 patients (83.6%) received peripheral blood stem cell grafts. GVHD prophylaxis always included a calcineurin inhibitor with the addition of methotrexate in 36 (29.5%) of patients, sirolimus in 60 (49.2%), Mycophenolate in 7 (5.7%), and post-transplant cyclophosphamide in 19 (15.6%) patients. Sixty-one patients (50%) had grade 2 or higher acute GVHD, and 19 (15.6%) had grade 3-4 acute GVHD. Extensive chronic GVHD was present in 81 (66.4%) of patients. Median follow-up of surviving patients was 59.3 months (3.3, 183.8) and overall the median follow-up was 30 months (0.55, 183.8). The estimated 12, 36, and 60-month Overall Survival (OS) of the cohort was 76.9% (95%CI 69.7-85), 66.1% (95% CI 57.7-75.6), and 58.4% (95% CI 49.4-69). Progression free survival (PFS) of the cohort at 12, 36, and 60 months was 71% (95% CI 63.2-79.7), 62% (95% CI 53.6-71.7) and 54.1% (45.1-65%) respectively. The median OS and PFS was not reached (Figure 1a,b). Fifty-two patients in the cohort died, 31 (59.6%) died of complications of treatment, 12 (23.1%) died of progression of disease, and 9 (17.3%) died of unknown causes. The day 100 cumulative incidence of non-relapse mortality (NRM) was 4.1% (1.7-9.7%) and the 1-year NRM was 17.2% (11.5-25.7%). Conclusion. This study shows excellent long term survival in patients who received an allo HCT for CML. And while, the modern treatment of CML largely relies on oral TKIs, in those patients who do not tolerate TKIs or fail available TKIs, allogeneic transplant remains an active, potentially curable therapy and should be considered. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Background: Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) relapse after allogeneic hematopoietic cell transplantation (HCT) is difficult to manage. One strategy to prevent this is tyrosine kinase inhibitor (TKI) maintenance post-HCT, but the vast majority of data discusses the use of imatinib in this setting, with few reports on newer generation TKIs (NG-TKI). Here, we present our institutional experience with TKI maintenance post-HCT. Methods: Ph+ ALL patients who underwent HCT and received TKI maintenance anytime post-HCT from 2003-2019 were included through retrospective chart review. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), and cumulative incidence of non-relapse mortality (NRM), cumulative incidence of relapse (CIR), and graft-vs-host disease (GVHD). OS and PFS were calculated via the Kaplan Meier method, NRM, CIR, and GVHD were calculated through a competing risk analysis, where CIR was used as a competing risk for NRM and GVHD, and NRM for CIR and GVHD. Results: 110 patients were included, and their baseline characteristics are described in Table 1. 45 (40.9%) patients received imatinib initially, and 65 (59.1%) received NG-TKI initially, of whom, 59 (90.8%) received dasatinib, 4 (6.2%) received nilotinib, and 2 (3.1%) received ponatinib. The median age (range) of the initial imatinib and NG-TKI groups were 42 years (19-64) and 47 (21-73), respectively. 25 (55.6%) vs 43 (66.2%) in the initial imatinib vs NG-TKI groups were >40 years, respectively. 18 (40.0%) vs 39 (60.0%) of the patients receiving initial imatinib vs NG-TKI were female (P=0.052). 20 (44.4%) vs 54 (83.1%) patients in the imatinib vs NG-TKI group underwent HCT ≥2010, respectively (P<0.001). 41 (91.1%) vs 57 (87.7%) in the imatinib vs NG-TKI groups underwent HCT in first complete remission (CR1) (P=0.76), and 21 (46.7%) vs 31 (47.7%) had no measurable residual disease (MRD) detected by PCR at the time of HCT, although 10 (22.2%) vs 10 (15.4%) did not have a PCR report at the time of HCT available (P=0.66). 42 patients (38.2%) required a dose reduction due to toxicity, and 67 patients (60.9%) experienced TKI interruption due to toxicity. Initial imatinib vs NG-TKI maintenance was discontinued in 20 (46.5%) vs 29 (44.6%) due to toxicity, respectively. The median cumulative initial TKI exposure in patients initially receiving imatinib and NG-TKI was 354 days (range, 6-4,473) and 301 days (range, 5-2,740), respectively. Reasons for TKI discontinuation are listed in Table 2. There was no difference in 5-year OS and PFS in patients receiving imatinib vs NG-TKI, 84.1% vs 69.8% (P=0.47) and 75.1% vs 62.5% (P=0.48), respectively. Likewise, 5-year NRM, 5-year relapse, and 4-year GVHD were similar between imatinib vs NG-TKI, 9.0% vs 18.3% (P=0.48), 15.9% vs 19.2% (P=0.92), and 40.7% vs 47.7% (P=0.47), respectively. Univariate analyses showed an improvement in OS and PFS in those who received ≥12 months of TKI maintenance vs those who received <12 months, hazard ratio (HR) 0.26 (95% confidence interval (CI), 0.12-0.55), P<0.001 and HR 0.33 (95% CI, 0.17-0.64), P<0.001. There was no difference in OS and PFS for those who completed ≥12 months of TKI maintenance based on initial TKI of choice, HR 0.85 (95% CI, 0.21-3.51), P=0.8 and HR 0.91 (95% CI, 0.28-2.94), P=0.9. Conclusions: Our findings demonstrate the challenges of delivering post-HCT TKI maintenance. Toxicity leading to TKI interruptions, discontinuation, and dose reduction was common. Post-transplant outcomes were comparable with imatinib and NG-TKI. Therefore, TKI selection for post-HCT maintenance should be based on patient tolerability to maximize TKI maintenance exposure. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Background: Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) has historically been associated with a poor prognosis. Allogeneic hematopoietic cell transplantation (HCT) is recommended in first complete remission (CR1). Strategies to decrease non-relapse mortality (NRM) and to increase the number of patients eligible to receive HCT have led to the utilization of reduced intensity conditioning (RIC) for patients unfit or too old for myeloablative conditioning (MAC), at the cost of a higher risk of relapse. Limited data exist comparing MAC vs. RIC HCT in Ph+ ALL. Here, we compared the outcomes of MAC- and RIC-HCT in Ph+ ALL. Methods: This was a single-center retrospective study examining patients with Ph+ ALL who underwent HCT from 2000-2019. The primary endpoint was progression free survival (PFS), while secondary endpoints include overall survival (OS), graft versus host disease free survival (GRFS), non-relapse mortality (NRM), and cumulative incidence of relapse (CIR), and GVHD. Survival estimates were calculated using the Kaplan-Meier method and differences were examined by the log-rank test. CIR and NRM were calculated using a competing risk analysis and differences were examined by Gray's test. Results: 185 patients were included, of whom, 131 (70.8%) underwent MAC, 128 (97.7%) of whom received total body irradiation (TBI)-based treatment, while 54 (29.2%) underwent RIC, 45 (83.3%) of whom received fludarabine plus melphalan (Flu/Mel). The median age (range) of the patients receiving MAC and RIC were 40 years (19-59) and 57 years (23-73), respectively. 66 (50.3%) vs 7 (13.0%) were ≤40 years in the MAC vs RIC groups (P<0.001). 66 (50.4%) vs 38 (70.4%) in the MAC vs RIC groups underwent HCT ≥2010. 115 (87.8%) vs 47 (87.0%) were in CR1 at the time of HCT in the MAC vs RIC groups (P=1.0), and 41 (31.3%) vs 16 (29.6) had measurable residual disease (MRD) by PCR at the time of HCT, although 34 (26.0%) vs 9 (16.7%) did not have a MRD pre-HCT report available (P=0.31), respectively. 110 (59.5%) received tyrosine kinase inhibitor (TKI) maintenance post-HCT, 73 (55.7%) in the MAC group vs 37 (68.5%) in the RIC group (P=0.14). The rest of their baseline characteristics are described in Table 1. In a sub-analysis of patients in MRD-negative CR1 at HCT, there was no statistically significant difference in 4-year PFS between MAC vs RIC, 71.1% vs 55.7% (P=0.12). PFS was similar in patients receiving TKI maintenance regardless of whether they received MAC vs RIC, hazard ratio 1.73 (95% confidence interval, 0.93-3.22; P=0.08). The 4-year NRM, CIR, and GVHD with MAC vs RIC were 25.6% vs 26.8% (P=0.50), 14.5% vs 21.4% (P=0.27), and 48.4% vs 46.3% (P=0.75), respectively. Conclusions: Patients with Ph+ ALL had similar PFS, OS, and GRFS when treated with MAC vs RIC. RIC-HCT is appropriate in those who would not be expected to tolerate MAC and may also be an acceptable strategy for younger patients when TKI maintenance post-HCT is administered. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

We report results of our prospective pilot trial evaluating safety/feasibility of peritransplantation ruxolitinib for myelofibrosis treatment. Primary objectives were to determine safety and maximum tolerated dose (MTD) of ruxolitinib. Ruxolitinib was administered at 2 dose levels (DLs) of 5 and 10 mg twice daily, with fludarabine/melphalan conditioning regimen and tacrolimus/sirolimus graft-versus-host disease (GVHD) prophylaxis. We enrolled 6 and 12 patients at DL1 and DL2, respectively. Median age at transplantation was 65 years (range, 25-73). Per Dynamic International Prognostic Scoring System, 4 patients were high and 14 intermediate risk. Peripheral blood stem cells were graft source from matched sibling (n = 5) or unrelated (n = 13) donor. At each DL, 1 patient developed dose-limiting toxicities (DLTs): grade 3 cardiac and gastrointestinal with grade 4 pulmonary DLTs in DL1, and grade 3 kidney injury in DL2. All patients achieved engraftment. Grade 2 to 4 and 3 to 4 acute GVHD cumulative incidence was 17% (95% confidence interval [CI], 6-47) and 11% (95% CI, 3-41), respectively. Cumulative incidence of 1-year chronic GVHD was 42% (95% CI, 24-74). With 22.6-month (range, 6.2-25.8) median follow-up in surviving patients, 1-year overall and progression-free survival were 77% (95% CI, 50-91) and 71% (95% CI, 44-87), respectively. Causes of death (n = 4) were cardiac arrest, GVHD, respiratory failure, and refractory GVHD of liver. Our results show peritransplantation ruxolitinib is safe and well tolerated at MTD of 10 mg twice daily and associated with dose-dependent pharmacokinetic and cytokine profile. Early efficacy data are highly promising in high-risk older patients with myelofibrosis. This trial was registered at www.clinicaltrials.gov as #NCT02917096.

N.K. – Research Funding – Amgen; Consulting – Medimmune/Astra Zeneca S.M. – Honoraria PleXus Communications, Physician Education Resource; Research Funding – Juno Therapeutics (Bristol-Myers Squibb Company), Allogene Therapeutics, Janssen Oncology, Takeda A.L. – Consulting/Honoraria BMS, Janssen, Amgen, Boehringer, Genmab; Research Funding – BMS, Janssen H.H. – Consultancy – Novartis, Research Funding – Celgene/BMS, Takeda E.S. Patents/ Royalties for CAR T cells to treat multiple myeloma, BMS; Consulting: BMS, Fate Therapeutics, Precision Biosciences; N.L. – Employed by Janssen; M.H. – Research Funding – Daiichi Sankyo, GSK, Amgen, Consultancy – Intellisphere D.C. – none M.S. –Consulting: Angiocrine Bioscience, Inc., Omeros Corporation, McKinsey & Company, Kite – A Gilead Company; Speaking engagement: i3Health (CME); G.S. – Research Funding – Amgen, Janssen; O.L. – MorphoSys; H.L. – Honoraria – Takeda, Sanofi, Pfizer; Advisory board – Takeda, Sanofi, Pfizer, Janssen, Celgene, Caelum, Abbvie, Karyopharm; Research Funding – Takeda, Janssen; Consultancy – Caelum, Karyopharm; M.A. – Honorarium: Invivoscribe, Inc.; C.H.: Honorarium, Invivoscribe; M.R. – none; A.D. – Consultancy – Roche, Physicians Education Resource, Seattle Genetics, Takeda, EUSA Pharma, Abbvie, Research Funding – Corvus, NC S.G. – Research Funding – Jazz, Kite, Actinuum, CSL Behring, Pfizer, Quintiles, Janssen, Amgen, Sanofi, Celgene/BMS, Adienne; O.L. – Consultancy – Adaptive, Amgen, Celgene/BMS, Janssen, Glenmark, Cellectis, Juno, Pfizer; Honoraria – Amgen, Celgene/BMS, Janssen, Glenmark, Cellectis, Seattle Genetics, Pfizer; Research Funding – Amgen, Celgene/BMS, Glenmark, Seattle Genetics, Karyopharm, Pfizer, Binding Site; Independent Data Monitoring Committee – Janssen, Takeda; D.M., E.T., B.D., M.S., K.W., K.J., D.V., A.S., T.P., A.D., S.D., C.T., U.S., S.L. report no disclosures.

The discovery of the tyrosine kinase inhibitor (TKI) imatinib in the early 2000's revolutionized the treatment and prognosis of patients with chronic myeloid leukemia (CML) [Hochhaus et al. in N Engl J Med 376:917-927, 2017]. The treatment of patients with CML has changed dramatically since the approval of imatinib and other TKIs. Before the TKI era, newly diagnosed patients would undergo HLA typing to try to identify a well-matched donor, and then proceed quickly to allogeneic hematopoietic cell transplantation (HCT). With the introduction of imatinib followed a few years later by dasatinib, nilotinib, then bosutinib, treatment approaches changed in a dramatic way. Transplantation is no longer an upfront treatment option for newly diagnosed CML patients, and in fact, it is very rarely used in the management of a patient with CML currently. The management of CML patients has been a model of personalized medicine or targeted therapy that is being emulated in the treatment of many other hematologic malignancies and solid tumors such as lung cancer [Soverini et al. in Mol Cancer 17:49, 2018]. The Philadelphia Chromosome (Ph) which leads to the formation of the BCR-ABL fusion gene and its product the BCR-ABL protein is the cause of CML. With effective targeting of this protein with the available TKIs, the disease is completely controllable if not curable for most patients. Life expectancy for patients with CML is essentially normal. Quality of life becomes an important goal including the potential for pregnancy, and ultimately the chance to discontinue all TKI therapy permanently. The three cases outlined below serve to highlight some of the important issues in the management of patients with CML in the post-TKI era.

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 (t(9;22] that gives rise to a BCR-ABL1 fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

Mismatched unrelated donors (MMUD) has improved access to hematopoietic cell transplantation (HCT) for underrepresented minority groups. However, MMUD HCT is historically associated with inferior outcomes primarily due to the increased risk of graft-versus-host disease (GvHD), when conventional calcineurin inhibitor-based GvHD prophylaxis is used. Post-transplant cyclophosphamide (PTCy) is an established and effective agent as part of GvHD prophylaxis post haploidentical HCT, which has been increasingly used in the matched donor HCT setting. To date, there have been no prospective studies reporting the efficacy of PTCy after peripheral blood stem cell (PBSC) MMUD HCT. Here, we conducted a pilot trial to estimate the GVHD-free relapse/progression-free survival (GRFS) at one-year post HCT and to evaluate the efficacy of PTCy as GvHD prophylaxis using either an ablative or reduced intensity conditioning regimen after PBSC MMUD HCT (NCT 03128359).

Hematopoietic cell transplantation (HCT) is the only potential curative option for many advanced hematologic diseases. Pediatrics, adolescent and young adult (PAYA) patients overall have less pre-HCT comorbidity or organ toxicity and lower transplant related morbidity and mortality risk compared to older adults. As such, a higher percentage of patients in this age group tend to receive myeloablative conditioning (MAC) over non-myeloablative regimens. Current alternative donor sources when a matched sibling donor (MSD) is not available include matched unrelated (MUD), umbilical cord blood (UCB), and haploidentical (Haplo) donors. While there are accumulating data comparing the HCT outcomes between MUD vs. Haplo or UCB in adult patients, the data are sparse in PAYA patients. In this retrospective study, we reviewed 314 consecutive patients aged 1-39 years who underwent their first allogeneic HCT using MAC at City of Hope between 1/2005-7/2018. Patients who received HCT from a matched sibling donor were excluded. Patients received HCT from either an 8/8 HLA MUD (n=196 [BM= 27%, PBSC= 73%]), UCB (n=83 [single: n=30, double: n=53]) or Haplo (n=35) donor. The most used MAC regimens were fractionated total body irradiation-based (n=234, 74%). All Haplo recipients got post-HCT cyclophosphamide (PTCy) as GVHD prophylaxis. To adjust for the difference in transplant era between UCB (predominantly performed in earlier years) and Haplo (carried out predominantly in more recent years) the comparative analyses were focused on Haplo or UCB vs. MUD. Univariate and multivariable Cox regression models were used to assess the impact of patient, disease, and treatment factors on overall survival (OS), progression-free survival (PFS), relapse/progression (RP), and non-relapse mortality (NRM). Median age of patients at the time of HCT was 24 years (range: 0.7-39), with 55% of patients being male. KPS was ≥80% in 88% of the patients and 25% had HCT-CI ≥ 2. The most common diagnoses included: ALL (48%), AML (41%), and MDS/CML (11%). DRI was high/very high in 44% of patients. Groups were balanced in general but patients in the Haplo group had higher HCT-CI (median: 2, p<0.01), more frequently had high/very high disease risk (49%, p<0.01) and higher KPS ≥80% (77%, p<0.01). Neutrophil engraftment was achieved at a median of 23 days (range: 10-94) in the UCB, 16 days (range: 12-32) in the Haplo and 15 days (range: 10-33) in the MUD (p<0.01). After a median follow up duration of 36 months (range: 5.9-36), 3-year OS was inferior among recipients of UCB-HCT (53%, 95% CI: 42-63) compared with the MUD (63%, 95% CI: 56-70; p=0.03), while similar between Haplo (62%, 95% CI:41-78) and MUD (p=0.82). The lower OS in UCB group was primarily due to the significantly higher NRM at 3 years (34%, 95% CI: 24-44) compared with the MUD (16%, 95%CI: 11-22, p<0.01); and 3-year NRM was not significantly different between Haplo (18%,95%CI: 6-34) and MUD (p= 0.99). On the contrary, the cumulative incidence of relapse (CIR) at 3 years was significantly lower in the UCB group (14%, 95%CI: 8-24) compared to MUD (29%, 95%CI: 23-36, p=0.01); the difference in CIR was not significant between Haplo (29%, 95% CI: 16-51) and MUD (p=0.81). PFS at 3 years was not significantly different among the three donor groups (p=0.43). Cumulative incidence of day 100 acute GvHD grade 2-4 was 61% (95% CI: 55-66) in the whole cohort, with no significant difference among the three groups (p=0.27). Cumulative incidence of chronic GVHD at 3 years was higher in the MUD group (66%: 95%CI: 59-72) compared to UCB (45%, 95%CI: 34-56, P<0.01) and Haplo (47%, 95% CI: 28-64, P=0.01). By multivariable analysis, patients with high/very high disease risk had worse OS (HR=1.8, 95% CI: 1.2-2.6, p<0.01) and PFS (HR=1.8, 95% CI: 1.3-2.5, p<0.01) and higher R/P (HR=2.3, 95% CI: 1.4-3.6, p<0.01). Neither Cord nor Haplo was significantly associated with OS compared with MUD when adjusted for Age, HCT CI, DRI, KPS, and HCT Era. In conclusion, our results indicated that in PAYA patients without a suitable MSD, outcomes of Haplo HCT are comparable to MUD HCT. By univariate analysis, UCB HCT was associated with a lower relapse rate compared to MUD. However, survival was worse in recipients of UCB HCT due to the higher NRM, possibly resulted from more infections and engraftment delays in these patients. Figure 1 Disclosures Ali: Incyte Corporation: Consultancy. Nakamura:Viracor: Consultancy; Kadmon Corporation: Other: Advisory board meeting; NapaJen Pharma: Consultancy; Celgene: Other: Support on seminar; Magenta Therapeutics: Other: Advisory board meeting; Alexion: Other: Support on a meeting presentation; Merck: Other: advisory board meeting; Kyowa-Kirin: Other: Support on a meeting presentation. Al Malki:Jazz Pharmacuticals, Inc: Consultancy; Neximmune: Consultancy; Rigel Pharma: Consultancy.

In a phase-2 study, the telomerase inhibitor imetelstat induced rapid hematologic responses in all patients with essential thrombocythemia who were refractory or intolerant to prior therapies. Significant molecular responses were achieved within 3-6 months in 81% of patients with phenotypic driver mutations in JAK2, CALR and MPL. Here, we investigated the dynamics of additional somatic mutations in response to imetelstat. At study entry, 50% of patients carried 1-5 additional mutations in the genes ASXL1, CBL, DNMT3A, EZH2, IDH1, SF3B1, TET2, TP53 and U2AF1. Three patients with baseline mutations also had late-emerging mutations in TP53, IDH1 and TET2. Most clones with additional mutations were responsive to imetelstat and decreased with the driver mutation, including the poor prognostic ASXL1, EZH2 and U2AF1 mutations while SF3B1 and TP53 mutations were associated with poorer molecular response. Overall, phenotypic driver mutation response was significantly deeper in patients without additional mutations (P = 0.04) and correlated with longer duration of response. In conclusion, this detailed molecular analysis of highly pretreated and partly resistant patients with essential thrombocythemia reveals a high individual patient complexity. Moreover, imetelstat demonstrates potential to inhibit efficiently co-incident mutations occurring in neoplastic clones in patients with essential thrombocythemia. (ClinicalTrials.gov number, NCT01243073. N Engl J Med 2015; 373:920-928, DOI: 10.1056/NEJMoa1503479.)

Wohlfahrtiimonas chitiniclastica and Ignatzschineria indica are rare causes of infection in humans and have been linked to infestation with fly larvae in open wounds. Both organisms are emerging causes of disease globally and co-infection resulting in bacteremia is rare. An 82-year-old male with bilateral lower extremity infections was hospitalized due to fall with associated right lower extremity pain. On exam, a maggot infested ulcer was identified on his right lower extremity. On day three of hospitalization, blood cultures grew gram-negative and gram-variable rods, and methicillin-resistant Staphylococcus aureus. Further analysis of the gram negative and gram variable rods revealed W. chitiniclastica and I. indica respectively. Both I. indica and W. chitiniclastica were pan sensitive to all antimicrobials tested with the exception of tetracyclines to which W. chitiniclastica was fully resistant and I. indica was intermediately sensitive. The patient was treated with two weeks of IV ceftriaxone and was discharged with plans to complete a six-week course of IV daptomycin due to MRSA bacteremia. All repeat blood cultures were negative. Until recently W. chitiniclastica and I. indica infections have been documented only in farm and feral animals. Major risk factors for infection include: poor hygiene, open wounds, peripheral vascular disease, and myiasis. Due to the rarity of infection, identification of both organisms can be difficult, therefore a high index of suspicion is required.

Drug-induced immune hemolytic anemia (DIIHA) is a rare cause of anemia. It is often difficult to distinguish from other causes of hemolytic anemia, thereby delaying diagnosis and treatment. Antibiotics, including penicillins and cephalosporins, are the drugs most often implicated in the development of DIIHA. Discontinuation of the offending agent is often sufficient for treatment. Here, we review the case of a 25-year-old Caucasian female who presented with jaundice and generalized weakness in the setting of outpatient treatment with amoxicillin-clavulanate due to sinus infection. Laboratory testing revealed transaminitis and hemolytic anemia. Direct antiglobulin test (DAT) revealed negative IgG and positive anti-C3. Cold agglutinin titer and Donath-Landsteiner test were negative. The patient was diagnosed with DIIHA most likely due to amoxicillin. She improved with drug cessation and a short course of glucocorticoids. Mechanism of DIIHA, workup, and management are subsequently reviewed.

Mortality in thyroid storm, without appropriate treatment, can rise as high as 100%. Thyroid storm coexisting with ischemic stroke is a rare presentation that further increases the risk of mortality. Early recognition and appropriate management are critical to the prevention of mortality and morbidity. Here, we review the case of a 63-year-old male presenting with new neurological deficits who was found to have thyroid storm; appropriate management of the co-existing conditions are also reviewed.

Background: Allogeneic hematopoietic cell transplantation (alloHCT) is the approach that offers the highest curative rate for acute myelogenous leukemia (AML) with intermediate or high-risk cytogenetics. Graft versus host disease (GvHD) has remained the main cause of post-transplantation mortality and morbidity, despite advances in prophylaxis and therapy, adding significant economic burden and affecting quality of life. It would be desirable to reduce the rate of GvHD among patients in complete remission (CR) without increasing the risk of relapse. In this study, we have developed a novel conditioning regimen of total marrow and lymphoid irradiation (TMLI) at 2000 cGy, together with post-transplant cyclophosphamide (PTCy), to 1) reduce the possibly increased risk of relapse from PTCy, by using escalated radiation doses of TMLI, as increasing radiation doses has the potential to decrease the post-transplantation relapse rate (Blood, vol 76, pp. 1867-1871, 1990); and 2) reduce the risk of chronic GvHD by using PTCy. The major goal of this pilot study of TMLI and PTCy (clinicaltrials.gov: NCT03467386), was to thus improve GvHD-free/relapse-free survival (GRFS), reported to be 45% from total body irradiation (TBI) and tacrolimus/sirolimus prophylaxis (BBMT, vol 26(2), pp. 292-299, 2020), in patients with AML in remission. Patients and Methods: A total of 18 patients were enrolled and treated (see Table) between March 2018 and December 2019. Key criteria were ages 18 to 60, first or second CR, minimal residual disease negative by multi-color flow cytometry, and normal organ function. TMLI was administered on days -4 to 0 without addition of chemotherapy. The radiation dose for all patients (n=18) was 2000 cGy, delivered in 200 cGy fractions twice daily. The radiation dose delivered to the liver and brain was kept at 1200 cGy. Remaining organs were considered non-targeted. All patients received peripheral blood stem cells on day 0. Cyclophosphamide was given on days +3 and +4, 50 mg/kg each day for GVHD prevention. Tacrolimus, 1 mg continuous infusion adjusted to maintain levels from 5 to 10 ng/mL was given from day +5 to day +90, and G-CSF 5 µg/kg daily was administered at day +5 until recovery of neutrophil counts. Endpoints included toxicity, GRFS at 1 year, engraftment, overall survival (OS), and non-relapse mortality (NRM). Toxicities were defined according to the Bearman and CTCAE 4.03 scales, the latter for hematologic toxicity. A patient safety lead-in segment (n=6) was conducted to ensure that there were no unexpected toxicities, allowing for a dose de-escalation to 1800 cGy. GRFS was defined as grade 3-4 acute GvHD, chronic GvHD requiring systemic treatment, relapse, or death (from any cause), whichever occurred first. Results: Bearman toxicity data are available for all patients. Among these patients, grade 2 toxicities were bladder toxicity and stomatitis. No grade 3-4 toxicities or toxicity-related deaths were observed. Acute GVHD (aGVHD) developed in 2 of patients (100-day Grade II-IV aGVHD: 11.1%, 95%CI: 1.7-30.4); of those, only 1 patient developed Grades III-IV (100-day Grade III-IV aGVHD: 5.6%, 95%CI: 0.3-23.1). Five patients developed mild chronic GVHD (1-year cGVHD rate: 28.6%, 95%CI: 7.5%-54.7%). The GRFS rate at 1 year was 59.3% (95% CI: 28.8-80.3) (Figure). The median follow up was 11.3 months (range 4.7 to 25.4) for surviving patients (n=17). All patients engrafted. Time to neutrophil and platelet recovery were 14 days (range 13-32 days) and 20 days (range 11-49 days), respectively. One-year estimates of OS and relapse-free survival were 100% and 80.8% (95% CI: 50.5-93.6), respectively (Figure). Disease relapse at 1 year was 19.2% (95% CI: 4.1-42.6). The estimates of NRM at 100 days and 1 year were both 0%. Relapsed disease after transplant occurred in 3 patients (16.7%). One patient died after relapse. Conclusions: 1) This chemotherapy-free conditioning regimen, together with PTCy and tacrolimus, is safe and feasible, with no NRM. 2) All patients achieved engraftment. 3) Participants with ≥1 year follow-up have discontinued immunosuppressive therapy, reducing financial burden and leading to improved quality of life. The preliminary results suggest an improved GRFS rate. A larger phase 2 trial is in preparation to corroborate these data. Disclosures Stein: Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau. Al Malki:Neximmune: Consultancy; Jazz Pharmacuticals, Inc: Consultancy; Rigel Pharma: Consultancy. Ali:Incyte Corporation: Consultancy. Aribi:Seattle Genetics: Consultancy. Marcucci:Novartis: Speakers Bureau; Takeda: Other: Research Support (Investigation Initiated Clinical Trial); Pfizer: Other: Research Support (Investigation Initiated Clinical Trial); Abbvie: Speakers Bureau; Merck: Other: Research Support (Investigation Initiated Clinical Trial); Iaso Bio: Membership on an entity's Board of Directors or advisory committees. Nakamura:Alexion: Other: Support on a meeting presentation; Kyowa-Kirin: Other: Support on a meeting presentation; Merck: Other: advisory board meeting; Celgene: Other: Support on seminar; Magenta Therapeutics: Other: Advisory board meeting; Viracor: Consultancy; Kadmon Corporation: Other: Advisory board meeting; NapaJen Pharma: Consultancy. Pullarkat:AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dova: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Salhotra:Celgene: Research Funding; Kadmon: Membership on an entity's Board of Directors or advisory committees.

Despite of the continuous increase in the number of volunteer donors available through the registry, many patients who require an allogeneic hematopoietic cell transplantation (HCT) cannot find a fully-matched donor. While a mismatched unrelated donor (MMUD) is frequently available, it is associated with inferior outcomes and increased risk of graft-versus-host disease (GvHD). Post-transplant cyclophosphamide (PTCy) has been effective in haploidentical HCT, and increasingly used in matched donor HCTs. However, limited data exist in MMUD setting. We conducted a prospective single center trial (NCT 03128359) of PTCy for MMUD HCT with the primary objective of estimating 1-year GvHD-free relapse/progression-free survival (GRFS). As of October 2019, all planned 39 patients have been enrolled with a median follow up of 11 months (range: 1-23). Here we present the preliminary estimate of 1-year GRFS and other HCT outcomes in two strata; myeloablative conditioning (n=19) using Fludarabine (90 mg/m2) and FTBI (1200 cGy) or reduced intensity conditioning (n=19) using Fludarabine (100 mg/m2) and Melphalan (140 mg/m2 or 100 mg/m2 if u003e60 years old). Patients between 0 to 75 years of age and KPS of ≥70% with hematologic malignancies undergoing HCT from a 7/8 HLA-matched (A-, B-, C-, and DR-) donor were eligible. Patients with donor specific antibodies to the mismatched HLA-locus were excluded. All patient received PBMCs (3-5 × 106/kg) followed by GVHD prophylaxis consisting of PTCy (50 mg/kg for 2 days), Tacrolimus (1 mg), and mycophenolate mofetil (1 gr 3 × a day). Median age at the time of HCT was 53 years (range: 21-72), and 50% of patients were male. Disease risk was low in 47% (n=18), intermediate in 37% (n=14), and high in 16% of the patients (n=6). At transplant, 29 patients were in complete remission, and 9 had active disease. HCT-CI was 0 in six (16%) and 1-2 in 15 (39%) and u003e2 in 17 (45%) patients. Donors’ median age was 32 years (range: 19-53) and donors were mismatched at HLA-A (n=14), -B (n=12), -C (n=8), or DR-loci (n=5). Median number of mismatches was 2 of 12 (range: 1-4). Female to male donor HCT was in 11% of recipients. Neutrophil engraftment occurred in all patients (median time to engraft: 16 days; range 13-35). One-year overall survival (OS) and GRFS were 92% (95% CI: 70-98) and 70% (95% CI: 51-83), respectively. Non-relapse mortality and relapse rate at 1 year were at 8% (95% CI: 2-29) and 13% (95% CI: 5-34), respectively. Cumulative incidence of day 100 acute GvHD grade 2-4 was 50% (95% CI: 35-71) and 1-year chronic GvHD was 56% (95% CI: 39-81). No severe chronic GvHD by the NIH criteria was observed. In conclusion, the data from our phase II trial of PTCy showed highly promising OS/GRFS in patients receiving 7/8 MMUD HCT, and that PTCy in MMUD setting offers an alternative and effective HCT approach for patients who do not have an available matched donor.

Cytomegalovirus reactivation commonly referred to as CMV infection (CMVi) is a frequent event after allogeneic hematopoietic cell transplantation (HCT), with studies associating CMVi within the first 100 days post-HCT with higher risk of non-relapse mortality (NRM) and decreased overall survival (OS). In addition, understanding the impact of CMVi on resource utilization during the primary HCT admission is critical. Together, this knowledge of epidemiology and resource utilization may be used to inform preventive strategies to minimize CMVi, e.g., use of antiviral agent letermovir. After receiving IRB approval, we retrospectively reviewed institutional electronic medical records and CMVi database from 824 patients who underwent their first allogeneic HCT between 2011 and 2016 at City of Hope (pre-letermovir era). Patients were censored at death, disease relapse or lost to follow up. Data collected: demographics, HCT indication, conditioning regimen, CMV serostatus of the donor and recipient (D/R), length of stay (LOS) for primary HCT admission (all allo HCT were performed as inpatient), readmission rates in first 100 days, and use of supportive care. CMV viral load of >250 genomic copies/ml constituted a diagnosis of CMVi. CMV viral load surveillance in MUD recipients began at engraftment or day +21 post-HCT, whichever occurred earlier. For Haplo and cord blood (CB) HCT, CMV viral load surveillance started on day +14. The primary endpoint of the study was LOS for HCT admission. Supportive care use, transfusions, growth factors and antiviral usage were secondary endpoints. The differences in resource utilization between different groups were examined by CMVi during the primary HCT admission period, using Wilcoxon test or chi-square test whenever appropriate. Median age of patients at the time of HCT was 52 years (range: 1-78), with 57% of patients being male. The most common diagnoses included: AML (39%), ALL (21%) and MDS/MPN (17%). Patients underwent MUD (n=627, 76%), Haplo (n=102, 12%), or CB-HCT (n=95, 12%), and 44% of patients received myeloablative conditioning regimen. Majority of the patients were CMV seropositive (83.7%). Graft source was peripheral blood stem cells in 75% of the recipients. Most commonly used graft-versus-host disease prophylaxis consisted of post-transplant cyclophosphamide (100%), Tacrolimus/sirolimus (83%), and cyclosporine/cellcept (78%) in Haplo, MUD, and CB-HCT recipients, respectively. During the primary HCT admission, rate of CMVi was 7%, 36% and 28% in all of MUD, Haplo, and CB-HCT, respectively (compared to 25%, 71.6%, and 50.5% in MUD, Haplo and CB-HCT respectively in the first 100 days after HCT). Rate of CMVi in CMV+ recipients was 8.2% in MUD, 41.6% Haplo and 34.2% in CB-HCT (Table 1). Majority of patients with CMVi received antiviral therapy (85.8%), with Haplo and CB-HCT more likely to be treated than MUD (p=0.023). LOS was longer among CMVi patients compared to no CMVi patients in each donor type, median of 59 vs. 36 days for the overall cohort (p<0.01). The difference in LOS by CMVi remained significant (p<0.001) in the multivariable regression model including donor type, graft source, primary diagnosis and conditioning intensity (Table 2). Filgastrim use was higher among CMVi patients than no CMVi patients in MUD (p<0.001), but not in Haplo or CB-HCT (p>0.2). Transfusion of packed red blood cells (PRBC) and platelet units were significantly higher among CMVi recipients of MUD and Haplo (p<0.02), but not CB-HCT (p>0.82). There was no significant difference in hospital readmission by CMVi across donor type in the first 100 days (p>0.5). In conclusion, the rate of CMVi during primary HCT admission was high, particularly in the Haplo and Cord HCT (>50% of the CMVi occurring within 100 days of HCT). Given the relatively high CMV viral load cut-off values and later CMV surveillance initiation, the rate could, in fact, have been underestimated in our cohort. CMVi during primary HCT admission was associated with significantly higher health care resource utilization; longer hospital LOS and supportive care utilization (CMV specific antiviral usage, transfusion and growth factors use). Prophylactic strategies to prevent early CMVi in alloHCT should be considered to decrease NRM and improve value based care delivery. Disclosures Dadwal: Shire/ Takeda: Research Funding; Karius: Research Funding; Astellas: Speakers Bureau; Janssen: Other: Advisory board meeting; Ansun Biopharma: Research Funding; Chimerix: Research Funding; Gilead: Research Funding; Merck: Consultancy, Honoraria, Other: Advisory board meeting, Research Funding, Speakers Bureau. Pullarkat:Dova: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Stein:Stemline: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Taplitz:Merck: Other: Immunocompromised Advisory Group. Al Malki:Neximmune: Consultancy; Rigel Pharma: Consultancy; Jazz Pharmacuticals, Inc: Consultancy. Nakamura:NapaJen Pharma: Consultancy; Magenta Therapeutics: Other: Advisory board meeting; Alexion: Other: Support on a meeting presentation; Kyowa-Kirin: Other: Support on a meeting presentation; Celgene: Other: Support on seminar; Viracor: Consultancy; Merck: Other: advisory board meeting; Kadmon Corporation: Other: Advisory board meeting.

The "7+3" regimen is recommended for treatment in patients with new diagnosis of acute myeloid leukemia (AML) who are fit for intensive chemotherapy. Patients with secondary AML (sAML) [i.e. AML evolving from antecedent hematologic disorders (AHD-AML) or after previous exposure to chemo/radiation therapy for unrelated cancer (t-AML)], have inferior outcomes with "7+3" regimen. A recent phase 3 study demonstrated superior CR rates and overall survival (OS) with upfront use of CPX-351 compared to "7+3" regimen in older patients (≥60 years) with sAML (Lancet et al JCO 2018). The combination of HMA+Ven is FDA approved for upfront treatment in newly diagnosed AML patients > 75 or those unfit for intensive chemotherapy based on CR+ CRi rates of 67% and median OS of 17.5 months. Herein, we compared the outcomes of older patients with sAML who received upfront treatment with either HMA+Ven or CPX-351 at our institution. Our analysis includes 47 consecutive patients with previously untreated sAML treated between 2018-2020 . Patients were treated with either HMA+Ven (n=27) or CPX-351 (n=20) based on physician preference. WHO criteria were used for the diagnosis AHD-AML and review of medical records for documenting exposure to leukemogenic agent for t-AML. Complete remission (CR) was defined by presence of <5% blasts in bone marrow (BM) aspirates. CR with blood count recovery (i.e., absolute neutrophil counts >1000/µL and platelets ≥100,000/µL) were defined as CRh (hematologic recovery) and CR without blood count recovery as CRi (incomplete blood count recovery). Minimal residual disease (MRD) assessment was done on day-28 BM aspirate using multiparametric flow cytometric assay with lower limit of sensitivity of 0.01%. Patients demographic and disease features are summarized in Table 1. Mean age (p=0.39), mean blast percentage in BM aspirate (P=0.82), high-risk cytogenetics (P=0.37) and high-risk molecular mutations (P=0.737) were similar in both treatment groups. Of the 27 cases of sAML in HMA+Ven group, 8 were t-AML arising after prior chemotherapy (Hodgkin's Disease n=2; paraganglioma, desmoid tumor, breast cancer, NHL, multiple myeloma, ALL: one each) while 19 were AHD-AML. In CPX-351 group, 6 cases were t-AML arising after prior chemotherapy (NHL n=2, breast cancer n=2, T-Lymphoblastic Lymphoma and colon cancer one each) while 14 were secondary to AHD. The mean number of cycles were 3.3 (range 1-18) in HMA+Ven group and 1.45 (1-3) in CPX-351 group. Two-sample t test was used to compare continuous and normally distributed covariates, such as age and BM blasts, between HMA+Ven or CPX-351 arms. Pearson Chi-square or Fisher exact test was used to assess the associations between treatment and clinical outcomes. Kaplan-Meier method and log-rank test were used to assess OS or LFS. A P value of ≤ 0.05 was considered as statistically significant. The CR rate in patients treated on HMA+Ven group was 78% (n=21; 95% CI: 58-91%) vs 50% (n=10; 95% CI: 27-73%) in CPX-351 group (P=0.047). CRi was achieved in 52% (n=14) patients in HMA+Ven group compared to 25%(n=5) patients in CPX-351 group(p=0.064). MRD negative remission was achieved in 52% (n=14) patients in HMA+Ven group and in 25% (n=5) patients in CPX-351 group (p=0.064). In HMA+Ven group, 52% patients (n=14) achieved remission after one cycle of therapy compared to 45% (n=9) patients in CPX-351 arm (p=0.642). With a median follow-up of 6.7 months for all patients, the median leukemia free-survival (LFS) for HMA+Ven vs CPX-351 treatments is 16.2 vs NA months (P = 0.098) and the median OS is 13.2 vs NA months (P = 0.395). Ten patients in each group (37% in HMA+Ven and 50% in CPX-351; p=0.47) underwent allo-HCT. At last follow up, 14 patients (52%) have died in HMA+Ven group from: relapsed AML (n=10), sepsis (n=2), congestive heart failure (n=1) and unknown (UK) in one patient, whereas in CPX-351 group, 8 patients (40%) have died from relapsed AML in (n=5), respiratory failure (n=2) and UK causes in one patient. In patients resistant to initial therapy, the median OS is 3.5 vs 6.0 months between HMA+ Ven and CPX-351 groups (P = 0.224). Conclusion: In patients presenting with sAML, upfront treatment with HMA+Ven is feasible and associated with significantly better CR rates and a favorable trend for higher rates of negative MRD compared to CPX-351. A randomized prospective trial in patients with sAML is warranted to determine the most effective frontline regimen in this high-risk AML subgroup. Disclosures Salhotra: Celgene: Research Funding; Kadmon: Membership on an entity's Board of Directors or advisory committees. Al Malki:Rigel Pharma: Consultancy; Neximmune: Consultancy; Jazz Pharmacuticals, Inc: Consultancy. Aribi:Seattle Genetics: Consultancy. Ali:Incyte Corporation: Consultancy. Budde:Gilead Sciences: Consultancy; Merck: Research Funding; Amgen: Research Funding; Kite, a Gilead Company: Consultancy; Mustang Therapeutics: Research Funding; AstraZeneca: Research Funding; Roche: Consultancy. Dadwal:Ansun Biopharma: Research Funding; Karius: Research Funding; Shire/ Takeda: Research Funding; Gilead: Research Funding; Merck: Consultancy, Honoraria, Other: Advisory board meeting, Research Funding, Speakers Bureau; Chimerix: Research Funding; Janssen: Other: Advisory board meeting; Astellas: Speakers Bureau. Nakamura:NapaJen Pharma: Consultancy; Kadmon Corporation: Other: Advisory board meeting; Viracor: Consultancy; Magenta Therapeutics: Other: Advisory board meeting; Celgene: Other: Support on seminar; Kyowa-Kirin: Other: Support on a meeting presentation; Alexion: Other: Support on a meeting presentation; Merck: Other: advisory board meeting. Stein:Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau. Marcucci:Takeda: Other: Research Support (Investigation Initiated Clinical Trial); Merck: Other: Research Support (Investigation Initiated Clinical Trial); Iaso Bio: Membership on an entity's Board of Directors or advisory committees; Abbvie: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Other: Research Support (Investigation Initiated Clinical Trial). Pullarkat:Dova: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: off label use of HMA+venetoclax in secondary AML

As the world of cellular therapy expands to include immune effector cell (IEC) products such as commercial chimeric antigen receptor (CAR) T cells, quality management (QM) professionals are faced with creating either new IEC stand-alone programs or expand existing hematopoietic cell transplantation (HCT) programs to promote patient safety and be aligned with quality, regulatory, and accreditation requirements. The team professionals at City of Hope (COH) recently expanded the quality HCT program to include IEC products and, in doi ng so, implemented new regulatory infrastructure while maintaining high quality patient care. At COH, we developed the quality structure of our cellular therapy program through collaborations between quality, regulatory, and CAR T patient care committees, which included physicians and nurse coordinators. To ensure the quality of our program, we monitor data collection and reporting, perform quarterly proactive audits of, for example, outcome analysis, and measure selected end-points for benchmarking purposes. QM professionals play a critical role in the monitoring and evaluation processes and provide guidance on how to implement accreditation requirements and what impact the requirements may have on care management. Here we describe the process by which COH expanded our HCT QM program to include IEC therapy. We share examples of how we developed our overall program structure and other key items such as how we addressed patient care management and accreditation to apprise other programs that wish to create and/or expand existing programs. (C) 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.