Although allogeneic hematopoietic stem cell transplantation (SCT) remains a potentially curative treatment option for several myeloid malignancies, despite the fact that the average age at disease onset for myeloid malignancies is approximately 70 years of age, its applicability in elderly patients is challenging. We retrospectively evaluated the outcomes of elderly SCT patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), using a nationwide Japanese registry database. We analyzed the data of 3609 patients ranging from 65 to 79 years of age with AML or MDS who underwent initial SCT between 2003 and 2022, while focusing on those 70 to 74 (n = 645) and 75 to 79 years old (n = 65). The 2-year overall survival (OS) and relapse-free survival rates for patients aged 65 to 69, 70 to 74, and 75 to 79 years were 40.9%, 38.0%, and 22.7%, and 48.4%, 47.2%, and 18.5%, respectively. Among patients categorized as low-risk at SCT, no significant differences were observed in the cumulative incidence of grade III to IV acute graft-versus-host disease (aGVHD), extensive chronic GVHD (cGVHD), non-relapse mortality, or relapse across all age groups. A multivariate analysis revealed that sex (male), diagnosis (AML), disease status (high-risk), SCT year (2003 to 2007), performance status (2-4), hematopoietic cell transplantation-specific comorbidity index (≥3), development of grade III to IV III-IV aGVHD, and extensive chronic GVHD significantly affected the OS. An older age (75 to 79) and the intensity of conditioning (reduced intensity) were factors indicating a trend toward an adverse prognosis. In these subgroups, significant interactions were observed between OS and SCT years, the time from diagnosis to SCT, and aGVHD. These findings suggest that SCT may be a potential curative option for selected elderly patients up to the mid-70s; however, careful patient selection and vigilant management of aGVHD are crucial factors for improving outcomes.

Poor prognostic factors, such as transfusion dependency and chromosomal risk, need to be considered in the indication of allogeneic hematopoietic cell transplantation (allo-HCT) for patients harboring myelodysplastic syndromes with less than 5% marrow blasts (MDS-Lo). We analyzed the post-transplant outcomes of 1229 MDS-Lo patients who received myeloablative (MAC)(n = 651), reduced-intensity (RIC)(n = 397), and non-myeloablative conditioning (NMAC) regimens (n = 181). The multivariate analysis revealed that the RIC group had better chronic graft-versus-host disease (GVHD)- and relapse-free survival (CRFS) (P = 0.021), and GVHD- and relapse-free survival (GRFS) than the MAC group (P = 0.001), while no significant differences were observed between the NMAC and MAC groups. In the subgroup analysis, the MAC group has better overall survival (P = 0.008) than the RIC group among patients with an HCT-comorbidity index (HCT-CI) score of 0, while the RIC group had better overall survival (P = 0.029) than the MAC group among those with an HCT-CI score ≥3. According to the type of conditioning regimen, total body irradiation 12 Gy-based MAC regimen showed better OS and CRFS than the other MAC regimen, and comparable outcomes to the RIC regimen. In conclusion, the RIC and NMAC regimens are promising options for MDS-Lo patients in addition to the MAC regimen.

Background: Various biomarkers have been developed and evaluated to predict the prognosis and complications of allogeneic hematopoietic cell transplantation (HCT). Most previous studies conducted on different biomarkers evaluated single effects such as those associated with inflammation, immunology, iron metabolism, and nutrition, and only a few studies have comprehensively analyzed markers. Objective: The study aimed to survey comprehensive multiple markers prior to HCT and extract those that significantly predict the outcomes. Study design: A prospective multicenter observational study was performed. (UMIN000013506) Patients undergoing HCT for hematologic diseases were consecutively enrolled. Besides the usual clinical biomarkers, serum samples for extra-clinical biomarkers were collected and cryopreserved before starting the conditioning regimen. A total of 32 candidate biomarkers were selected, 23 from hematology, biochemistry, immunology, nutrition, and iron metabolism, and 9 from composite markers. Based on the area under the curve (AUC) values for survival, promising biomarkers was extracted. Internal validation for these markers was applied based on bootstrap methods. Setting the cut-off values for them, log-rank test was applied and outcomes including overall survival (OS), relapse, and non-relapse mortality (NRM) were evaluated using multivariate analyses. Furthermore, detailed analysis including transplant-related complications and external validation were conducted focusing on C-reactive protein (CRP) to platelet (Plt) ratio. Results: A total of 152 patients with hematologic malignancies were enrolled from April 2014 to March 2017. CRP, soluble interleukin-2 receptor (IL2R), CRP to albumin (Alb) ratio, CRP to Plt ratio, Plt to IL2R ratio, and IL2R to Alb ratio were identified as promising markers. Internal validation successfully confirmed their reliability of AUC and multivariate analysis demonstrated the statistical significance between the higher and the lower markers. Above all, a higher CRP to Plt ratio was significantly associated with a lower OS (hazard ratio [HR] 2.77; 95% confidence interval [CI] 1.30-5.91; P = 0.008) and higher non-relapse mortality rates (HR 2.79; 95%CI 1.14-6.80; P = 0.024) at 180 days. Furthermore, univariate analysis showed that a higher CRP to Plt ratio was significantly associated with a higher incidence of sinusoidal obstructive syndrome (P < 0.001) and bloodstream infection (P = 0.027). An external validation test confirmed the significance of the CRP to Plt ratio for these outcomes. Conclusion: The multicenter prospective observational study successfully identified significant biomarkers in patients with hematologic malignancies who received HCT. In particular, CRP to Plt ratio was identified as a novel and useful biomarker for predicting transplant outcomes. Further

Despite the emergence of monoclonal antibodies, the prognosis of patients with multiple myeloma (MM) with extramedullary disease remains poor. The present report describes a rare case of daratumumab-refractory MM that was successfully treated with elotuzumab, pomalidomide and dexamethasone. A 66-year-old male patient diagnosed with MM was treated with bortezomib, lenalidomide and dexamethasone, followed by high-dose chemotherapy and autologous stem cell transplantation. Thereafter, the patient was treated with lenalidomide and dexamethasone as maintenance therapy. This was changed to daratumumab, bortezomib and dexamethasone when new paraskeletal lesions were identified, resulting in marked tumor shrinkage. After 15 months, an increase in serum monoclonal protein levels, development of a skeletal lesion in the right second rib and extramedullary disease of the right thoracic mediastinal lymph nodes were noted. Treatment with elotuzumab, pomalidomide and dexamethasone (EPd) resulted in expeditious symptomatic improvement and regression of the lesions. Notably, during daratumumab, bortezomib and dexamethasone treatment, lymphocyte counts gradually increased to a level at which elotuzumab was sufficiently effective. EPd might be a promising strategy for the treatment of patients with relapsed extramedullary MM while on daratumumab treatment.

Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an only therapeutic option to provide a curative outcome for atypical chronic myeloid leukemia (aCML). Due to its rarity, the optimal transplant procedures have not been established. We herein conducted a nationwide retrospective study focusing on the prognostic impacts of transplant procedures, such as conditioning intensity and donor source, in aCML patients. Methods This study included aCML patients (i) who were 16 years or older, (ii) who received their first allo-HSCT between 2003 and 2021, and (iii) who were reported as negative for the presence of the t(9;22)(q34;q11) cytogenetic translocation and for the BCR::ABL1 transcript. The clinical data of 74 patients were collected from the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation. To identify variables potentially affecting outcomes, overall survival (OS), graft-versus-host disease (GVHD)- and relapse-free survival (GRFS), and chronic GVHD-free survival (CRFS) were examined using Cox proportional hazards regression models, and cumulative incidences of relapse (CIR), non-relapse mortality (NRM), neutrophil engraftment, and platelet recovery were investigated using the Fine and Gray proportional hazards model for the subdistribution of competing risks. Results In a total of 74 patients, median age at allo-HSCT was 54years (range, 18-72). Regarding transplant procedures, 54 (73.0%) and 20 (27.0%) patients received myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC), respectively; and 11 (14.9%), 35 (47.3%), 19 (25.7%), and 9 (12.2%) patients used HLA-matched related donor (HMR), unrelated bone marrow/peripheral blood stem cell (UR-BM/PBSC), unrelated cord blood (U-CB), and HLA-haploidentical related (Haplo-R) donor, respectively. In allo-HSCT from Haplo-R donor, 6 out of 9 patients used post-transplant cyclophosphamide as GVHD prophylaxis. Over the four time periods (2003-2007, 2008-2012, 2013-2017, and 2018-2021), there was a progressive increase in the use of RIC regimen and U-CB/Haplo-R donor. As for condition intensity, no significant difference was observed in the unadjusted probabilities of OS, CRFS, GRFS, CIR, NRM, and neutrophil engraftment incidence between MAC and RIC regimens, but the unadjusted incidence of platelet recovery tend to be low in RIC regimen than MAC regimen with a marginal significance (P=0.09). In the multivariate analysis, RIC regimen showed no significant difference in OS, CRFS, GRFS, CIR, NRM, and neutrophil engraftment compared to MAC regimen. RIC regimen showed a significant lower incidence of platelet recovery than MAC regimen (Hazard ratio (HR) [95% confidential interval], 0.40 [0.16-0.99]; P=0.048). In MAC and RIC regimens, the 3-year adjusted probability of OS was 50.1% and 74.7%; the 3-year adjusted CIR was 44.3% and 33.1%; and the 3-year adjusted NRM was 13.5% and 22.8%, respectively. Regarding donor source, the unadjusted probabilities of OS, CRFS, GRFS, CIR, and NRM were not significant difference among four donor sources. The unadjusted incidence of hematopoietic recovery was significant lower in U-CB than HMR: neutrophil engraftment (P=0.008) and platelet recovery (P=0.002). In the multivariate analysis, the use of alternative donor (UR-BM/PBSC, U-CB, and Haplo-R donor) did not have any significant impact on OS, CRFS, GRFS, CIR, and NRM compared to HMR. U-CB significantly correlated with lower neutrophil engraftment (HR, 0.26 [0.10-0.64]; P=0.003) and platelet recovery (HR, 0.17 [0.07-0.44]; P<0.001) than HMR. In HMR, UR-BM/PBSC, U-CB, and Haplo-R donor, the 3-year adjusted probability of OS was 76.7%, 68.3%, 37.5%, and 60.8%; the 3-year adjusted CIR was 41.9%, 42.0%, 37.9%, and 38.5%; and the 3-year adjusted NRM was 12.0%, 26.2%, 27.4%, and 0.0%, respectively. Conclusion This study demonstrated that RIC regimen can provide the long-term remission in aCML patients as well as MAC regimen. Another significant point is that no significant difference of the post-transplant outcomes was observed in donor sources. Although careful management for hematopoietic recovery is necessary in allo-HSCT using RIC regimen and U-CB, the use of RIC regimen and alternative donor would be a feasible strategy to achieve curative outcomes in aCML patients.

Patients with recurrent peripheral T-cell lymphoma (PTCL) after allogeneic hematopoietic cell transplantation (HCT) have dismal outcomes. Nodal PTCL with the T follicular helper phenotype (PTCL-TFH) is uniquely sensitive to histone deacetylase inhibitors compared to non-TFH phenotypes. We report the case of a 19-year-old man who experienced recurrence of PTCL-TFH shortly after allogeneic HCT and subsequently achieved durable remission with romidepsin. Before HCT, the patient had refractory disease after CHOP and ESHAP chemotherapies but achieved a partial response after two cycles of romidepsin as salvage treatment. HLA-haploidentical peripheral blood stem cell transplantation was performed using conditioning with fludarabine 180 mg/sqm, melphalan 80 mg/sqm, and total body irradiation 2 Gy, and graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide. One month after HCT, disease progression was observed in the lung. Romidepsin was readministered every 2 weeks at a reduced dose of 12 mg/sqm. After two cycles of romidepsin, the patient achieved a complete metabolic response without severe GVHD or other non-hematological toxicities. Romidepsin was discontinued after seven treatment cycles due to prolonged lymphopenia. The patient remains in complete remission 30 months after the last dose of romidepsin. Our experience suggests that romidepsin could be safely administered soon after allogeneic transplantation.

Therapy-related acute myeloid leukemia (t-AML) is a therapeutic challenge as a late complication of chemotherapy (CHT) and/or radiotherapy (RT) for primary malignancy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) presents itself as a curative approach. To establish the optimal allo-HSCT strategy for t-AML, we evaluated the relationship between characteristics of primary malignancy and allo-HSCT outcomes. Patients with t-AML or de novo acute myeloid leukemia (AML) who underwent first allo-HSCT in Japan from 2011 to 2018 were identified using a nationwide database. The detailed background of t-AML was obtained by additional questionnaires. Multivariate analysis and propensity score matching (PSM) analysis were performed to detect the prognostic factors associated with t-AML and compare outcomes with de novo AML. We analyzed 285 t-AML and 6761 de novo AML patients. In patients with t-AML, receiving both CHT and RT for primary malignancy was an independent poor-risk factor for relapse and overall survival (OS) (hazard ratio (HR) 1.62; p = 0.029 and HR 1.65; p = 0.009, reference: CHT alone group), whereas other primary malignancy-related factors had no effect on the outcome. Compared to the CHT alone group, complex karyotypes were significantly increased in the CHT + RT group (86.1% vs. 57.5%, p = 0.007). In the PSM cohort, t-AML patients with prior CHT and RT had significantly worse 3-year OS than those with de novo AML (25.2% and 42.7%; p = 0.009). Our results suggest that prior CHT and RT for primary malignancy may be associated with increased relapse and worse OS of allo-HSCT in t-AML.

Nelarabine is an effective treatment for T-cell acute lymphoblastic leukemia/lymphoma. Myelopathy is a rare but serious adverse event associated with this drug. Three patients who received nelarabine at the National Cancer Center Hospital from December 2014 to March 2021 developed myelopathy 20 days before, 12 days after, and 29 days after allogeneic hematopoietic cell transplantation (allo-HCT), respectively. Magnetic resonance imaging showed that two of the patients had lesions in the dorsal column or medulla oblongata, and one had no abnormalities in the head or spine. Despite treatment with intravenous immunoglobulin and methylprednisolone, all patients became unable to walk. One patient died on day 101 after allo-HCT due to progressive neurotoxicity. The other two patients showed spontaneous improvement in neurological symptoms, but one died of mucormycosis on day 476. Autopsy revealed spongiosis in the posterior funiculus in both patients who died, and also in the medulla oblongata in one patient. In the surviving patient, positron emission tomography on day 84 showed abnormal accumulation, suggesting continued inflammation. These cases demonstrated pathophysiological features of nelarabine-induced myelopathy and indicate that allo-HCT may worsen the condition. It is necessary to elucidate the underlying mechanism and establish diagnostic methods and therapies.

Patients with recurrent adult T-cell leukemia/lymphoma (ATL) after allogeneic hematopoietic cell transplantation (allo-HCT) have a dismal prognosis. We retrospectively evaluated the safety and efficacy of lenalidomide (LEN) in 11 consecutive patients with recurrent ATL after allo-HCT. The median time from allo-HCT to ATL recurrence was 111 days (range, 20-1476), and that from allo-HCT to the initiation of LEN was 162 days (range, 43-1560). The median initial daily dose of LEN was 10 mg (range, 5-25), and the median duration of LEN treatment was 37 days (range, 3-1078). Three patients (27%) achieved complete response and two (18%) achieved partial response (PR). The rates of complete or PR according to the involved site were 57% for skin and 50% for nodal or extranodal lesions. With a median follow-up of 1033 days (range, 601-1465) among survivors, the 1-year probability of overall survival (OS) after ATL recurrence was 55%. Grade >= 3 toxicities included cytopenia (n = 4), superficial vein thrombosis (n = 1), and deep vein thrombosis (n = 1). Graft-versus-host disease (GVHD) newly developed in five patients (45%) and worsened in four patients (36%). The median duration from the initiation of LEN to GVHD onset or worsening was 5 days (range, 1-9). GVHD was manageable in all patients. Seven patients received mogamulizumab (MOG) for recurrent ATL before LEN treatment. The overall response rates to LEN were 57% in patients who had previously received MOG and 25% in those who had not. The 1-year probabilities of OS after recurrent ATL were 71% in patients who had previously received MOG and 25% in those who had not. Although cytopenia and GVHD are common among patients with recurrent ATL after allo-HCT, LEN may improve survival. Administering MOG before LEN may augment treatment efficacy in the allo-HCT population.

Background Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option frequently used in patients with acute lymphoblastic leukemia (ALL). However, relapse after allo-HCT remains the main concern because it is associated with poor outcomes, with a long-term survival rate < 10 %. There is no standard treatment for patients with ALL who relapsed after allo-HCT. Second allo-HCT (allo-HCT2) is a curative treatment option for patients with ALL who relapsed after the first allo-HCT (allo-HCT1). However, data on allo-HCT2 in patients with ALL are limited, and the indications and outcomes of allo-HCT2 are unclear. Therefore, this study aimed to investigate the outcomes and prognostic factors of patients who underwent allo-HCT2 after ALL relapse. Methods This study included 425 adult patients with ALL who underwent allo-HCT2 after relapse between January 2001 and December 2020. The primary endpoint was 2-year overall survival (OS), which was evaluated using the log-rank test. Prognostic factors for the primary endpoint were evaluated using the multivariable Cox proportional hazards model. The variables considered in the Cox proportional hazards model are listed in the Table. The impacts of the candidate factors are shown as hazard ratios (HRs) and 95% confidence intervals (CIs). Additionally, we performed an analysis stratified by disease and disease status because Philadelphia chromosome (Ph)-positive B-ALL could affect the treatment and disease status at allo-HCT2 and the outcome. Results The median age at allo-HCT2 was 36 years (interquartile range; 27-48 years) and 220 patients (52%) were male. According to the Eastern Cooperative Oncology Group, 94 patients (22%) had a performance status of > 2. There were 235 patients (55%) with Ph-negative B-ALL, 122 patients (29%) with Ph-positive B-ALL, and 68 patients (16%) with T-ALL. Regarding disease status at allo-HCT2, 217 patients (51%) had any complete response (CR). One hundred forty-eight patients (35%) received myeloablative conditioning regimen. Ninety patients (21%) received related bone marrow (BM) or peripheral blood (PB) transplantation, 137 patients (32%) received unrelated BM or PB transplantation, and 198 patients (47%) received unrelated cord blood (CB) transplantation. The median observation time of survivor after allo-HCT2 was 22.3 (interquartile range; 6.3-82.5) months and 2-year OS was 28.0% (95% CI, 23.7-32.4). After stratified disease and disease status, the 2-year OS was 56.5% (95% CI, 44.6-66.8), 31.7% (95% CI, 24.0-39.7), 21.5% (95% CI, 10.6-34.9), and 13.1% (95% CI, 8.4-18.8) in any CR (Ph-positive B-ALL), any CR (other), active disease (Ph-positive B-ALL), and active disease (other), respectively ( P < 0.001) (Figure). In multivariable analysis, Ph-positive B-ALL (HR, 0.48; 95% CI, 0.36-0.65; P < 0.001), tacrolimus-based GVHD prophylaxis at allo-HCT2 (HR, 0.72; 95% CI, 0.54-0.95; P = 0.022) were identified as significantly positive prognostic factors for 2-year OS, while allo-HCT1 to allo-HCT2 < 12 months (HR, 1.38; 95% CI, 1.02-1.88; P = 0.038), relapse within 12 months after allo-HCT1 (HR, 1.37; 95% CI, 1.01-1.85; P = 0.043), ECOG PS > 2 (HR, 1.89; 95% CI, 1.44-2.49; P < 0.001), active disease at allo-HCT2 (HR, 1.88; 95% CI, 1.46-2.42; P < 0.001), unrelated BM or PB transplantation at allo-HCT2 (HR, 1.78; 95% CI, 1.22-2.59; P = 0.003), and CB transplantation at allo-HCT2 (HR, 1.54; 95% CI, 1.09-2.18; P = 0.013) were identified as significantly negative prognostic factors for 2-year OS. Conclusion In this study, we demonstrate that the 2-year OS was 28.0% in patients with ALL who underwent allo-HCT2 and identified the prognostic factors that may guide patients to benefit from allo-HCT2.

Response evaluation of carbon-ion radiotherapy poses a diagnostic challenge. Due to its functional aspects, fluorodeoxyglucose positron emission tomography (FDG/PET) has a role in the diagnosis of photon radiation therapy. In addition, several studies suggested that FDG/PET may be useful to select the optimal site for performing a diagnostic biopsy. Here, we report a 73-year-old female in which FDG/PET was effective in determining the recurrence of liposarcoma and the therapeutic effect. Based on the results of FDG/PET, we could make a pathologic definitive diagnosis and selectively performing carbon-ion radiotherapy for active tumors.

Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides curative outcomes in patients with myelodysplastic syndromes (MDS). The blast percentage in MDS is one of the important factors to utilize allo-HSCT, and the other disease-related factors, such as transfusion dependency and chromosomal risk, are crucial to consider whether patients harboring MDS with less than 5% of marrow blasts (MDS-Lo) undergo to allo-HSCT. However, the prognostic impacts of conditioning intensity in MDS-Lo patients are still unclear. We here conducted a nationwide retrospective study to clarify the prognostic factor and investigate the optimal conditioning intensity for MDS-Lo. Methods In this study, patients diagnosed as the other than refractory anemia with excess blasts (RAEB)-1 and -2 according to the WHO classification (marrow blasts <5% and peripheral blood blasts <1%) were considered to be MDS-Lo. The clinical data of 1,229 de novo MDS-Lo patients (i) who had stayed MDS-Lo from diagnosis to transplantation and (ii) who underwent their initial allo-HSCT between January 2001 and December 2020 were collected from the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation. Cox proportional hazards regression models were used to evaluate variables potentially affecting overall survival (OS), chronic graft-versus-host disease (GVHD)-free survival (CRFS), and GVHD- and relapse-free survival (GRFS). Fine and Gray proportional hazards models were used to evaluate variables potentially affecting cumulative incidences of relapse (CIR) and non-relapse mortality (NRM), using cumulative incidence curves to accommodate competing events. Results In a total of 1,229 patients, 651, 397, and 181 patients received myeloablative conditioning (MAC), reduced-intensity conditioning (RIC), and non-myeloablative conditioning (NMAC) groups, respectively. The estimated 3-year OS rates were 63.3%, 61.0%, and 69.7% in MAC, RIC, and NMAC groups, respectively; the estimated 3-year CRFS rates were 41.1%, 43.9%, and 47.2% in MAC, RIC, and NMAC groups, respectively; the estimated 3-year GRFS rates were 27.5%, 33.4%, and 35.4% in MAC, RIC, and NMAC groups, respectively; the estimated 3-year CIR were 11.9%, 14.2%, and 16.0% in MAC, RIC, and NMAC groups, respectively; and the estimated 3-year NRM were 29.8%, 31.0%, and 24.7% in MAC, RIC, and NMAC groups, respectively. The multivariate analyses revealed four factors affecting lower OS: older recipient's age (Hazard ratio (HR) [95% confidential interval], 1.70 [1.28-2.24]; P<0.001 for 40-59 years)(HR, 2.32 [1.71-3.15]; P<0.001 for 60 years or older), performance status 2-4 at HSCT (HR, 1.84 [1.32-2.57]; P<0.001), the history of infection before HSCT (HR, 2.12 [1.55-2.89]; P<0.001), and high number of red blood cell (RBC) transfusion before HSCT (HR, 1.65 [1.35-2.02]; P<0.001). These factors also negatively affected CRFS, GRFS, and NRM. In addition, poor cytogenetic risk group was associated with worse OS (HR, 1.66 [1.32-2.09]; P<0.001), CRFS (HR, 1.48 [1.22-1.80]; P<0.001), and GRFS (HR, 1.36 [1.14-1.64]; P=0.001) but not CIR. There was no significant difference of OS, CRFS, GRFS, CIR, and NRM in either RIC or NMAC group compared to MAC group. We next performed the subgroups analysis based on the prognostic factors. The subgroup analysis for the comparison between MAC and RIC regimens showed the better OS of MAC regimen among patients with low number of RBC transfusion (HR, 1.33 [1.01-1,75]; P=0.039). The subgroup analysis for the comparison between RIC and NMAC regimens revealed the better OS of NAMC regimen among patients aged <40 years (HR, 0.43 [0.19-0.96]; P=0.038), no history of infection (HR, 0.67 [0.50-0.91]; P=0.009), and good cytogenetic risk (HR, 0.54 [0.38-0.83]; P=0.004). Conclusion This study showed the prognostic factors on the post-transplant outcomes among MDS-Lo patients, and no significant difference of conditioning intensity in the entire population. Furthermore, we found the factors (the number of RBC transfusion, patient's age, the history of infection, and cytogenetic risk) potentially affecting the selection of conditioning intensity. These findings would improve the management for transplant candidates with MDS-Lo.

We herein report a case of peripheral blood stem cell transplantation (PBSCT) involving a donor with EDTA-induced pseudothrombocytopenia (PTCP). The apheresis product was inspected for 24 h and there was no platelet clumping or thrombocytopenia. In the first 14 months after PBSCT, there has been no transfer of PTCP symptoms.

Background: The 2008 World Health Organization (WHO) classification proposed a new entity in childhood myelodysplastic syndrome (MDS), refractory cytopenia of childhood (RCC). The spectrum of patients with RCC is wide, ranging from patients with severe hypocellular bone marrow (BM) and mild dysplasia (hypocellular RCC) to those with normocellular BM and distinct dysplasia meeting the criteria for refractory cytopenia with multilineage dysplasia (RCMD) defined for adults with MDS. The term of RCMD was revised to MDS with multilineage dysplasia in the 2017 WHO classification. In Japan, children who meet the criteria for RCMD have been diagnosed as RCMD distinguished from hypocellular RCC. Although hematopoietic cell transplantation (HCT) is a curative treatment for RCMD in children, there have been few reports of the outcomes of HCT for children with RCMD. Patients and Methods: To clarify the outcomes of HCT for children with RCMD, we retrospectively analyzed the clinical data in children (<16 years) with RCMD who underwent the first HCT from 2010 to 2021 and registered in the Japan Society for Hematopoietic Cell Transplantation Registry, and compared with those in adolescents and young adults (AYA; ≥16, <40 years) with RCMD who underwent the first HCT during the same study period. During the study period, 195 patients with RCMD (children, 69; AYA, 126) underwent HCT. The stem cell source was BM in 138 (children, 58; AYA, 80), peripheral blood (PB) in 27 (children, 2; AYA, 25), and cord blood (CB) in 30 patients (children, 9; AYA, 21). Myeloablative conditioning (MAC) regimen was defined as the use of total body irradiation (TBI) ≥8 Gy (MAC-TBI) and the administration of busulfan (BU) >8 mg/kg (MAC-BU). All other regimens were included in reduced intensity conditioning (RIC) regimen. Results: We retrospectively analyzed 195 patients with RCMD (male, 105; female, 90). The median age at HCT was 8 years (range, 0-15) in children and 29 years (range, 16-39) in AYA. Of the 195 patients, 20 (29%) and 52 (41%) had abnormal karyotypes in children and AYA, respectively. Of the patients who underwent HCT, 68 were from related (children, 22; AYA, 46), and 127 from unrelated (children, 47; AYA, 80) donors. MAC-BU was used for 46 (children, 9; AYA, 37), MAC-TBI for 51 (children, 1; AYA, 50), and RIC for 98 (children, 59; AYA, 39) patients. Of the 195 patients, 8 (children, 3; AYA, 5) developed primary graft failure, 16 (children, 5; AYA, 11) secondary graft failure, 10 (children, 3; AYA, 7) disease relapse, and 11 (children, 2; AYA, 9) secondary tumor. Twenty-four (children, 5; AYA, 19) patients died of HCT-related complications and four AYA of disease relapse. The 5-year overall survival (OS) rate was significantly higher in children (93%) than in AYA (82%) (p = 0.04). The 5-year event-free survival (EFS) rate was 76% in children and 64% in AYA. The 1-month cumulative incidence (CI) of neutrophil engraftment was 93% in children and 94% in AYA. The 5-year CI of relapse was 6% in AYA and 2% in children. The 5-year CI of treatment-related mortality (TRM) was 16% in AYA and 7% in children. The 5-year CI of graft failure was 12% in children and 12% in AYA. The 3-year CI of chronic graft-versus-host disease (GVHD) was significantly higher in AYA (37%) than in children (21%) (p = 0.04), while there was no difference in the 3-month CI of acute GVHD (gradeⅡ-Ⅳ) between children (35%) and AYA (39%). In children, the 5-year OS and EFS rates were significantly lower in CB (67% and 42%) than in BM/PB (97% and 81%) (p < 0.01 and p < 0.01), respectively, while the 5-year OS and EFS rates were not different between CB (91% and 76%) and BM/PB (80% and 62%) in AYA, respectively. Of the 59 children who underwent HCT using RIC, 43 without abnormal karyotypes showed 95% and 16 with abnormal karyotypes showed 88% in the 5-year OS rate. Even in AYA, there was no difference in the 5-year OS rate between RIC and MAC in both groups with (RIC, n = 14, 76%; MAC, n =38, 72%) and without (RIC, n = 25, 81%; MAC, n = 49, 90%) abnormal karyotypes. Conclusions: HCT for children with RCMD showed better OS rate than that for AYA with RCMD. HCT using RIC regimen provided good outcomes for RCMD in children with or without abnormal karyotypes. Even in AYA, HCT using RIC regimen showed OS rate comparable to MAC regimen in both groups with and without abnormal karyotypes.

Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only curative treatment for myelodysplastic syndromes (MDS), although predicting post-transplant outcomes remains inconclusive. This study evaluated patients who underwent allo-HCT for MDS to identify prognostic factors and develop a clinical risk model.Methods: We evaluated 55 patients between June 2000 and March 2015 to identify prognostic factors and develop a model for three-year overall survival (OS) and event-free survival (EFS). Cox regression analysis was performed on four factors: age ≥55 years; Hematopoietic Cell Transplant-Comorbidity Index >2; intermediate or worse cytogenetic status based on revised International Prognostic Scoring System; and unrelated donor status associated with poor OS in the univariate analysis. A clinical risk model was constructed using the sum of the regression coefficients and evaluated using receiver operating characteristic analysis and five-fold cross-validation.Results: Patient median age was 51 (range: 30–67) years. Median follow-up was 45.8 (range: 1.27–193) months; the three-year OS and EFS rates were 61.8% and 56.4%, respectively. The areas under the curves (AUCs) for OS and EFS were 0.738 and 0.778, respectively, and the average AUC for 50 times five-fold cross-validation were 0.711 and 0.723 for three-year OS and EFS, respectively.Conclusion: A four-clinical-risk-factor model that could effectively predict post-transplantation outcomes and help decision-making in MDS treatment was developed.

Removal of incompatible red blood cells (RBCs) and separation of mononuclear cells (MNCs) is usually required to avoid intravascular hemolysis during infusion of ABO-mismatched allogeneic bone marrow transplantation (BMT). We sought to clarify the effect of the MNC separation process on engraftment. We retrospectively reviewed 78 patients who received transplants of unrelated bone marrow with MNC separation between 2011 and 2020. The median volume depletion rate was 89.4% (78.9-96.2), the RBC depletion rate was 83.7% (64.8-92.2), and the recovery rate of total nucleated cells (TNCs) was 31.1% (9.1–66.7). Engraftment was observed in 76 of 78 (97.4%) patients. Median time for neutrophil recovery was 18 days (range: 11-43); for platelet recovery, 33 days (17-151); and for reticulocyte recovery, 28 days (15-1468). When post-processing TNC count was cut off at 1.2×108/kg, neutrophil (p=0.03) and platelet (p=0.01) engraftments were significantly faster in the higher group, but reticulocyte engraftment did not differ significantly between the two groups. The risk of neutrophil engraftment delay was higher for post-processing TNC lower 1.2×108/kg (HR:1.54, 95% CI:1.01-2.35, p=0.04), and platelet engraftment delay was observed in post-processing TNC lower than 1.2×108/kg (HR:1.7, 95% CI:1.10-2.64, p=0.01) and pre-disease condition (HR:0.54, 95% CI:0.33-0.89, p=0.01).

PURPOSE:Physical activity (PA) interventions positively affect the physical function (PF) in patients with advanced cancer. However, patients must remain motivated during the intervention. We report a case wherein a smartphone application for PA intervention was useful in motivating the patient to improve adherence.METHODS:A 40-year-old woman underwent an allogeneic hematopoietic cell transplantation (allo-HCT) for an advanced extranodal natural killer/T-cell lymphoma. On day 6, she developed the posterior reversible encephalopathy syndrome. She was managed in the intensive care unit for 3 days, and her PF declined markedly. We initiated a smartphone-based PA intervention from day 35. She was instructed to maintain a PA diary for self-monitoring of the daily steps and to set a new step-count goal every week.RESULTS:The PA and PF improved within a short period thereafter. However, she developed severe acute graft-versus-host disease and was administered with high-dose systemic corticosteroids from day 49. The PA, PF, and quality of life (QOL) decreased again. The intervention was continued for 5 months with a high adherence. The PA, PF, and QOL improved gradually. She resumed independent activities of daily living and was discharged on day 202.CONCLUSION:Smartphone-based PA intervention may be effective against post-allo-HCT physical dysfunction.

Letermovir is commonly used for CMV prophylaxis after allogeneic hematopoietic cell transplantation (HCT). Pharmacokinetic studies have shown an increase in tacrolimus exposure among healthy volunteers who took letermovir. However, studies in HCT recipients are needed because these patients are typically using concomitant antifungals with different degrees of CYP3A4 inhibition that may further interact with tacrolimus pharmacokinetics. In this study, we retrospectively evaluated the kinetics of tacrolimus concentration after letermovir discontinuation by type of concomitant azole antifungal in 57 HCT recipients. The median fold change in tacrolimus concentration-to-dose (C/D) ratio after discontinuing letermovir was 0.64 (range 0.43–0.99) with fluconazole and 1.10 (range 0.59–1.73) with voriconazole (p < 0.001). The tacrolimus C/D ratio decreased ≥ 30% after discontinuing letermovir (p < 0.001) in 66% of patients on fluconazole and 9% on voriconazole. Among patients whose tacrolimus C/D ratio decreased ≥ 30%, three (9%) patients in the fluconazole group and one (4%) in the voriconazole group experienced worsening of GVHD. Careful monitoring of tacrolimus concentration is important after letermovir discontinuation to avoid worsening of GVHD due to decreased tacrolimus concentration.

The prognosis of acute myeloid leukemia (AML) patients with der(1;7)(q10;p10) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) is unclear due to its rarity. We retrospectively analyzed 151 AML patients with der(1;7)(q10;p10) and compared the findings with those of 853 AML patients with monosomy 7 or chromosome 7q deletion (-7/del(7q)) using Japanese nationwide registry data. The der(1;7)(q10;p10) group showed significantly better transplant outcomes than the -7/del(7q) group. In the multivariate analysis of the der(1;7)(q10;p10) group, additional chromosomal abnormalities and a poor performance status significantly influenced the survival. In conclusion, allo-SCT is a feasible treatment option for AML patients with der(1;7)(q10;p10).