Background Delayed platelet engraftment is a significant complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Objectives This retrospective study evaluates the efficacy and safety of hetrombopag, an oral thrombopoietin receptor agonist, in promoting platelet engraftment post-allo-HSCT. Design Retrospective observational cohort study. Methods A cohort of 133 patients was analyzed, including 68 treated with hetrombopag post-transplant and 65 controls. Cumulative incidence function evaluated platelet engraftment, with propensity score matching and competing risk analysis to strengthen robustness. Factors associated with platelet engraftment were examined using multivariate Cox models with time-dependent coding of hetrombopag exposure. Results Hetrombopag significantly reduced the time to overall response (OR: 15.0 days vs. 20.0 days; p = 0.009) and complete response (CR: 17.5 days vs. 34.0 days; p < 0.001). The cumulative incidence of CR was higher in the hetrombopag group (92.78% vs. 86.58%; p = 0.001), with a significantly shorter median time to CR (19 days vs. 38 days) defined by the cumulative incidence function. Multivariate Cox regression identified hetrombopag as a protective factor for platelet recovery (HR: 2.04; p = 0.004). Competing risk and PSM analyses confirmed hetrombopag’s role in faster platelet engraftment. The treatment was well-tolerated, with manageable mild liver enzyme elevations and hypomagnesemia but no grade 3/4 adverse events. Conclusion Hetrombopag significantly accelerates platelet engraftment and has a favorable safety profile, suggesting its potential as a therapeutic adjunct in managing thrombocytopenia post-allo-HSCT. This study complements and validates findings from prior prospective studies, providing external confirmation in a real-world cohort.

Although post-transplant cyclophosphamide (PTCy) is widely used to prevent graft-versus-host disease (GVHD), its protective effect remains inadequate in patients undergoing myeloablative haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). We retrospectively evaluated the efficacy of PTCy combined with either pre-transplant or post-transplant antithymocyte globulin (ATG) for GVHD prevention in 114 haplo-PBSCT recipients. The PTCy+FTATG group (n = 74) received ATG at a total dose of 5 mg/kg on days -3 to -1, together with PTCy at 25 mg/kg on days +3 and +4. The PTCy+PTATG group (n = 40) received PTCy at 50 mg/kg on days +3 and +4, followed by ATG at 2.5 mg/kg on day +8. Both univariate and multivariate analyses showed that PTCy+FTATG prophylaxis significantly lowered the risk of grade II-IV acute GVHD (9.5% vs 27.5% [HR 0.24; 95% CI: 0.10-0.59; P = 0.002]) and grade III-IV acute GVHD (5.4% vs 17.5% [HR 0.19; 95% CI: 0.07-0.54; P = 0.002]). The 2-year cumulative incidence of chronic GVHD was 16.7% in the PTCy+FTATG group and 27.5% in the PTCy+PTATG group (P = 0.15). At 2 years, overall survival (OS), progression-free survival (PFS), and graft-versus-host disease-free relapse-free survival (GRFS) were 87.8% vs 72.5% (P = 0.04), 82.2% vs 65.0% (P = 0.03), and 78.1% vs 55.0% (P = 0.005), respectively. These results suggest that half-dose PTCy combined with low-dose pre-transplant ATG may be a promising strategy for GVHD prophylaxis.

Background Major ABO-group incompatibility increases the risk of delayed erythroid engraftment, and other immunological complications post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Blinatumomab, a CD19/CD3 bispecific T-cell engager antibody, has demonstrated efficacy in eradicating CD19 positive B lymphocytes. However, its role in optimizing immune complications after an ABO incompatible transplant remains unreported. Methods We performed a single-center retrospective analysis on 42 consecutive B-ALL patients who received major or bidirectional ABO-incompatible allogeneic HSCT between June 2021 to June 2025. Patients were divided into three groups: group A (incompatible major ABO-group with blinatumomab treatment, n=13), group B (incompatible ABO-group without blinatumomab treatment, n=10), and group C (compatible ABO-group with blinatumomab treatment, n=19). The primary endpoint was the time to transfusion independence (defined as the first day without red blood cell transfusion for 3 consecutive months). The secondary endpoints included total red blood cell transfusion volume, time to blood type conversion, immune reconstitution indicators, and other survival outcomes. Multi-group comparisons were performed using the Kruskal-Wallis test, and survival analysis was evaluated using the Kaplan-Meier method. Results The median times to transfusion independence in group A , group B, and group C were 1 (range, 1-13), 54 (1-119), and 1 (1-67) days, respectively. Compared to group B, blinatumomab shortened the time to transfusion independence in group A (P=0.011), reduced the red blood cell transfusion volume (group A vs group B: 0 (0-5.50) vs 8.5 (0-16) U; P=0.031) and relapse rate (2-year relapse rate: 12.50% vs 40.00%; P=0.041), and improved overall survival (2-year survival rate: 87.50% vs 60.00%, P=0.046). No statistical differences were observed between group A and group C (P>0.05). However, no statistical differences existed among the three groups in neutrophil engraftment time (group A vs group B vs group C: 12 (9,14) vs 13 (12,18) vs 13 (10,17) days), platelet engraftment time (13 (9,22) vs 15 (12,22) vs 14 (10,27) days), time to blood type conversion (group A vs group B: 106 (54,175) vs 111 (101,293) days), post-transplant B lymphocyte count (3 (0,73) vs 10.5 (0,355) vs 2 (0,522) cells/μL), CD4+ cell count (70 (1,146) vs 45 (1,419) vs 81 (2,486) cells/μL), incidence of grade II-IV acute graft-versus-host disease (aGVHD) (100-day grade II-IV aGVHD rate: 15.40% vs 31.60% vs 20.00%), and incidence of chronic graft-versus-host disease (cGVHD) (3-year cGVHD rate: 23.10% vs 20% vs 27%) (P>0.05). In the assessment of immune function, post-transplant globulin levels (25.20 (17.50,31.40) vs 17.10 (14,25.40) g/L, P=0.036) and IgG levels (9.30 (5.62,13.60) vs 5.73 (2.58,11) g/L, P=0.041) in group B were higher than those in group C, but the levels in group A (globulin: 18.80 (14.70,24.80) g/L; IgG: 6.19 (4.01,10.80) g/L) fell in between the two groups with no statistical significance (P>0.05). ConclusionsBlinatumomab improves time to erythroid engraftment after a major ABO-incompatible transplant. Disclosures No relevant conflicts of interest to declare.

BackgroundAggressive natural killer (NK) cell leukemia (ANKL) is a rare NK cell neoplasm associated with Epstein-Barr virus (EBV) infection. Programmed cell death protein 1 (PD-1) blockade, which is successful in extranodal NK/T-cell lymphoma and EBV-related hemophagocytic lymphohistiocytosis, is considered to have a potential role in managing ANKL.ObjectivesThis study aims to characterize ANKL clinically and evaluate the prognostic impact of anti-PD-1 antibody treatment.MethodsWe retrospectively analyzed the clinical characteristics and treatment regimens of ANKL patients from March 2009 to October 2023 in a single center. Data on clinical characteristics, treatment regimens and prognosis were collected from medical records. Overall survival (OS) of different risk groups was analyzed by Kaplan-Meier method. The least absolute shrinkage and selection operator (LASSO)-penalized Cox regression was used to identify the potential prognostic factors of ANKL.ResultsFrom March 2009 to October 2023 a total of 71 ANKL were retrieved with an OS of 2.0 months. Seven patients (9.9%) received PD-1 antibodies combined with various chemotherapies; thirty-five patients (49.3%) received asparaginase as part of chemotherapy; and eight patients (11.3%) received allogeneic HSCT after induction chemotherapy. Among patients who did not undergo allogeneic hematopoietic stem transplantation (HSCT), patients who received PD-1 antibodies as part of chemotherapy exhibited a superior OS than those without PD-1 antibodies (5.4 vs 1.6 months, p=0.035). The 1-year OS rate was 43% in the PD-1 subgroup compared with only 4% in the non-PD-1 subgroup. LASSO-Cox multivariate analysis revealed that PD-1 antibodies-containing regimens were associated with better survival (hazard ratio [HR]=0.349, 95% CI: 0.145~0.840, p=0.019). So was it with HSCT and asparaginase (HR=0.267, 95% CI=0.101~0.701 and HR=0.355, 95% CI=0.206~0.613, respectively).ConclusionANKL still had a poor outcome in the past decade. Integration of anti-PD-1 antibody into chemotherapeutic therapy significantly improved the survival of ANKL. The prolonged survival attributed to PD-1 blockade could provide critical opportunities for patients awaiting HSCT.

Background: The development of tyrosine kinase inhibitor (TKI) therapy has positively impacted the survival rates of patients with chronic myeloid leukemia (CML). It is common in medical practice to adjust the dosage of TKI downward because of TKI-associated adverse events, financial burden, comorbidity, or an attempt at treatment-free remission. Objectives: This investigation sought to explore the feasibility of employing a reduced dosage of TKI for treating CML. Design: This was a retrospective study. Methods: Patients with CML in its chronic phase who had been on a reduced dose of TKI for a minimum of 3 months for various reasons in a practical clinical environment, irrespective of molecular response, were included. Regular molecular monitoring was performed, and changes in adverse events were recorded after dose reduction. Results: This research included a total of 144 participants. Upon reducing the dosage, 136 of 144 patients achieved major molecular response or deeper, and 132 of 144 achieved molecular response 4 (MR4). Following a median observation period of 16 months, the calculated 1- and 2-year survival rates free from MR4 failure were estimated to be 96.5% (95% CI: 90.8–98.7) and 90.5% (95% CI: 81.3–95.3), respectively. MR4 failure-free survival was better in patients with longer MR4 durations (⩾34 months) before dose reduction ( p = 0.02). The median interval from dose reduction to MR4 loss was 15 months. Improved TKI-associated adverse events after dose reduction were observed in 61.3% of patients. Conclusion: Lowering the TKI dose can effectively preserve a deep molecular response over time while relieving adverse events caused by TKIs.

Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improves patient outcomes, yet post-transplant relapse remains a major cause of mortality. Currently, there is no widely accepted maintenance therapy for B-cell acute lymphoblastic leukemia (B-ALL) patients following transplantation. Blinatumomab, the first bispecific T-cell engager targeting CD19 and CD3, has demonstrated significant efficacy in relapsed B-ALL and minimal residual disease (MRD) clearance. This study explores the efficacy of blinatumomab as maintenance therapy post-allo-HSCT in B-ALL. Methods This prospective, single-arm clinical trial includes B-ALL patients scheduled to allo-HSCT. All patients underwent myeloablative conditioning. Peripheral stem-cell grafts were obtained from HLA-matched sibling donors (MSD), matched unrelated donors (MUD), or haploidentical donors (HID). Post-transplantation acute graft versus host disease (GvHD) prophylaxis included cyclophosphamide and cyclosporine, with mycophenolate mofetil added from day +5 to day +35 for HID transplant recipients. Patients without active GvHD were enrolled in this trial. The first cycle of blinatumomab maintenance started between 75-90 days post-transplant and was administered every three months up to one year. Blinatumomab was continuously administered with an initial dosage of 8 μg/day for the first two days, followed by 16 μg/day for days 3-7, 3 vials per cycle. Follow-up examinations were scheduled at +1, +2, +3, +4, +6, +9, +12, +18-, and +24-months post-transplant. Results Nineteen patients (7 males, 12 females) with a median age of 34 years (range 16-58) were enrolled. Ten patients were diagnosed with Philadelphia chromosome-positive ALL. All patients achieved complete remission (CR) before transplantation (13 of CR1, 5 of CR2, and 1 of CR3), and 17 achieved MRD clearance. The other two patients exhibited MRD levels between 10-5 and 10-3. Allo-HSCT was performed using MSD in 1 patient, MUD in 1 patient, and HID in 17 patients. By day +30 post-ASCT, all patients achieved CR with negtive MRD. During maintenance therapy, two patients discontinued treatment due to drug-related seizures. Among the remaining 17 patients, 10 completed four cycles of blinatumomab, 2 completed three cycles, 1 completed two cycles, and 4 completed one cycle. In the first cycle, five patients experienced drug-related adverse events (5/17, 29.4%), including 2 with grade I cytokine release syndrome (CRS) (11.8%), 1 with grade I immune effector cell-associated neurotoxicity syndrome (ICANS) (5.9%), 1 with grade I headache (5.9%), 2 with grade I nausea (11.8%), and 1 with grade I rash (5.9%). In the following cycles, the adverse reaction gradually decreases. No patient developed a new onset or progression of GvHD after maintenance therapy. No patient died of the adverse event of blinatumomab maintenance. We paired another 39 B-ALL patients who underwent allo-SCT in the same period of time without post-transplant maintenance therapy as a control group. We compared the incidence of relapse, GvHD, and survival of both groups. No relapse occurred in the blinatumomab group, but 15 in the control group. The 1-year cumulative relapse rates were 0.0% and 39.5%, respectively, with a significant difference (P=0.009). One patient died of septicemia in the blinatumomab group at 19.3 months post-transplant, and 14 died of relapse in the control group. The 18-month leukemia-free survival rates were 100% and 60.5%, respectively, with a significant difference (P=0.037). The 18-month overall survival rates were 100% and 73.4%, respectively. The grade II-IV acute GvHD incidences were 25.3% and 15.9%, respectively. Grade III-IV acute GVHD incidences were 7.6% and 5.3%, respectively. No significant differences were observed between the two groups. Conclusion Blinatumomab maintenance therapy following allo-HSCT is safe. Although the dosage of blinatumomab was markedly lower than recommended, it significantly reduced post-transplant relapse and improved leukemia-free survival for B-ALL patients. Further research is needed to confirm its long-term efficacy and safety.

Acute graft versus host disease (aGvHD) is a severe complication that arises in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and remains the primary cause of nonrelapse mortality (NRM). The MAGIC algorithm probability (MAP) has been proposed to identify patients at intermediate and high risk of developing aGvHD. The levels of suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3α (Reg3α) were assessed, and MAP was calculated on days 7, 14, 21, and 28 after allo-HSCT. Based on the MAP results, patients were classified into low-, intermediate-, or high-risk groups for the development of aGvHD. Random assignment was performed to allocate intermediate- or high-risk patients to receive preemptive therapy with methylprednisolone or not. The 100-day cumulative incidences of grade 2 or higher (35.5% ± 8.6%) and grade 3 or higher (12.9% ± 6.0%) aGvHD in the methylprednisolone group were significantly lower than those in the control group (66.7% ± 7.9%, p = .01; 42.9% ± 8.4%, p = .01), and similar to those observed in the low-risk group (31.7% ± 7.3%, p = .75; 2.4% ± 2.4%, p = .08). The 6-month cumulative incidences of NRM were 14.1% ± 6.6%, 22.7% ± 7.1%, and 2.4% ± 2.4% in the methylprednisolone, control, and low-risk groups, respectively, with no significant difference between the methylprednisolone and control groups (p = .29). Methylprednisolone did not increase infections (p = .34). The 100-day cumulative incidences of cytomegalovirus (CMV) reactivation were 67.7% ± 8.4%, 65.6% ± 8.4%, and 46.3% ± 7.8% (p = .08), and those of grade 2 or higher hemorrhagic cystitis were 29.0% ± 8.2%, 45.2% ± 8.9% and 22.0% ± 6.5% (p = .11) in the methylprednisolone, control, and low-risk groups, respectively. MAP-guided preemptive therapy for aGvHD is promising. The long-term efficacy and safety remain to be investigated.

Abstract Background: Chemotherapy-induced nausea and vomiting (CINV) remains a serious concern for haematological patients, especially for those receiving conditioning regimens. We conducted a retrospective study to evaluate the efficacy of netupitant/palonosetron (NEPA) compared with 5-hydroxytryptamine-3 receptor antagonist (5HT3RA) without additional dexamethasone (DEX) in preventing CINV in patients receiving multiday conditioning regimens. Methods: Patients undergoing haemopoietic stem cell transplantation at West China Hospital between September 2019 and September 2022 were included and divided into NEPA or 5HT3RA groups. The rates of patients with complete response (CR: no emesis and no use of rescue medication), complete control (CC: CR without significant nausea), no vomiting and no significant nausea were used to assess CINV outcomes. Results: A total of 213 haematopoietic stem cell transplant (HSCT) patients were included in this study. The percentage of patients with CR was significantly higher in the NEPA group than in the 5HT3RA group during the overall phase (71.7% vs. 32.7%), acute phase (78.3% vs. 43.0%) and delayed phase (84.9% vs. 58.9%). Rates for other outcomes were significantly superior in the NEPA group than in the 5HT3RA group during all phases (p < 0.001). Conclusion: Our study demonstrated that NEPA was superior to 5HT3RA in preventing CINV during all phases in patients undergoing multiday conditioning regimens.

Introduction: The delayed platelet engraftment is a common complication in allogeneic hematopoietic stem cell transplantation (allo-HSCT), which elevates treatment-related mortality and impairs quality of life. Although some studies reported that platelet engraftment after allo-HSCT was promoted by thrombopoietin-receptor agonists (TPO-RAs), the recommended detailed TPO-RA administration is still lacking. This prospective, single-center, investigator-initiated pilot study aims to explore the efficacy and safety of herombopag, a second-generation TPO-RA, to stimulate platelet engraftment in haploidentical allo-HSCT (haplo-HSCT). Methods: A total of 36 patients (median age 38; range 15-59 years) with anaplastic anemia, myelodysplastic syndrome, acute leukemia, granulocytic sarcoma, or primary hemophagocytic lymphohistiocytosis were enrolled between November 2021 and June 2023. All patients received haplo-HSCT and post-transplant cyclophosphamide for acute graft-versus-host disease (aGVHD) prophylaxis. Patients received herombopag from day+5 post-HSCT until platelet>100,000/µL, disease progression, intolerable toxicity, or withdrawal of informed consent. The dose of herombopag was 5 mg/day initially and reduced to 2.5 mg/day when platelet>75,000/µL. Complete platelet engraftment (CPE) was defined as a platelet count exceeding 50,000/μl for seven consecutive days without transfusion. Partial platelet engraftment (PPE) was defined as a platelet count exceeding 20,000/μl for seven consecutive days without transfusion. The objective response included both CPE and PPE. The primary endpoint was the 21-day cumulative incidence and 28-day cumulative incidence of CPE and objective response after haplo-HSCT. The secondary endpoints were time to CPE, time to objective response, platelet transfusion units, aGVHD, relapse, non-relapse mortality, and safety. Results: The patients received herombopag treatment for a median of 15 days. The 21-day cumulative incidence of CPE was 55.6%, and that of objective response was 77.8%. The 28-day cumulative incidence of CPE was 69.4%, and that of objective response was 80.6%. The median time to objective response was 20.5 (95%CI 17-27) days. The median time to CPE was 23 (95%CI 10-33) days. The mean units of platelet transfusions required within 30 days after HSCT was 6.7. The median follow-up time was 12.1 months. The one-year overall survival rate was 85.3% (95%CI 72.8%-99.8%). Two patients died of aGVHD and two patients died of lung infection. Four Patients (11.1%) experienced molecular relapse. The cumulative incidence of grade III-IV aGVHD was 16.7%. Furthermore, cytomegalovirus reactivation occurred in 13 patients (36.1%). The most common herombopag-related adverse events were hypomagnesemia (61.1%), increased GGT (52.8%), increased ALT (38.9%), and increased bilirubin (19.4%). No grade III/IV adverse events were observed. Conclusion: Herombopag significantly stimulates platelet engraftment in haplo-HSCT patients and has a favorable safety profile. Further research with a larger sample size and longer follow-up period is required to confirm its optimal use.

Natural killer (NK) cell based immunotherapy is an emerging strategy in hematologic malignancies because allogeneic NK cells can provide potent antitumor immunity without inducing graft-versus-host disease. Thus, we expanded cord blood-derived NK (CB-NK) cells ex vivo from random (MHC mismatched and KIR mismatched) donors, and investigate the feasibility and efficacy of repeated infusions CB-NK cells as maintenance therapy after autologous hematopoietic stem cell transplantation (ASCT). Thirty-one patients with acute myeloid leukemia and high-risk lymphoma received ASCT and the adoptive CB-NK cell multiple infusions for maintenance therapy. Patients received a median dose of 5.98 × 10 7 /kg (range, 1.87-17.69 × 10 7 /kg) CB-NK cells and 23 patients completed four infusions, 8 patients received three infusions. Only mild infusion reactions occurred in 15.5% of 116 infusions. Compared to a contemporaneous cohort of 90 patients who did not receive NK cell therapy, the adoptive transfer of CB-NK cells as maintenance treatment showed a tendency of difference in decreasing the relapse rate between CB-NK group and control group (9.7% vs 24.4%). The patients who receiving NK cell infusions had a better PFS and OS than controls (4 year PFS, 84.4 ± 8.3% vs 73.5 ± 5.4%; and 4 year OS, 100% vs 78.1 ± 5.4%) . These findings demonstrate safety and validity of maintenance therapy using CB-NK cells multiple infusions after ASCT, and it is worthy of further clinical trial verification.

Introduction The influence of pre-transplant leukemic load on relapse and long-term survival is well-documented among patients with B-cell acute lymphoblastic leukemia (B-ALL). Blinatumomab, a bispecific T cell engager, has shown promising results as an effective treatment for relapsed B-ALL. However, the dosage (28μg/day) and duration (28 days of continuous infusion) of blinatumomab have been predominantly determined in a relapsed leukemia context. Therefore, in the minimal residual disease (MRD) scenario, the standard dosing may exceed the required amount, potentially leading to increased toxicity, delays in transitioning to the scheduled transplant, and superfluous economic expenditure. Methods We enrolled B-ALL patients with ≤10% MRD who were slated for allogeneic hematopoietic stem cell transplantation (ASCT). MRD was quantified via multi-parameter flow cytometry or polymerase chain reaction (PCR) for the target gene. Blinatumomab therapy began at 8 μg/day, gradually escalating to 28 μg/day over only 5-10 days. Bone marrow cells were harvested post-blinatumomab therapy. Upon acquiring MRD negativity, patients proceeded to the transplantation protocol. All patients underwent myeloablative conditioning with chidamide, fludarabine, cytarabine, and busulfan. Peripheral stem-cell grafts were harvested from HLA-matched sibling donors (MSD), matched unrelated donors (MUD), or haploidentical donors (HID). Post-transplantation acute GVHD prophylaxis consisted of cyclophosphamide and cyclosporine. For HID transplant recipients, mycophenolate mofetil was added from day +5 to day +35. Follow-up examinations were scheduled at +1, +2, +3, +4, +6, +9, +12, +18, and +24 months post-transplant. Results Our study cohort comprised 20 patients (13 females, 7 males), median age 35.5 years (range 15-58). Patient and disease characteristics are summarized in Table 1. During the blinatumomab therapy, 8 patients (40%) experienced grade 1 cytokine release syndrome (CRS), and 1 patient (5%) experienced grade 2 CRS, with no instances of grade 3 or higher CRS observed. All patients achieved complete remission (CR) and MRD clearance evaluated by flow cytometry following blinatumomab treatment. Eleven patients were diagnosed with Philadelphia chromosome-positive ALL, and 5 of them didn't achieve MRD clearance evaluated by PCR. Allo-SCT was conducted following blinatumomab at a median interval of 5.5 days (range 1-29) using MSD in 4 patients, MUD in 2 patients, and HID in 14 patients. The median time to neutrophil and platelet engraftment was 12 days (range 9-17) and 13 days (range 9-28), respectively. The median follow-up duration was 10.2 months (range 2-21.7). By day +30 post-ASCT, all patients achieved CR and MRD clearance with full donor chimerism. Acute GVHD (aGVHD) (grades II-IV) and (grades III-IV) incidences were recorded at 10.0% and 5.3% respectively (Figure 1A). One fatality occurred due to COVID-19-associated pulmonary aspergillosis 7.2 months post-transplantation. Among the 18 evaluable patients, the estimated 1-year cumulative incidence of chronic GVHD (cGVHD) was 44.4%, with no instances of severe cGVHD observed (Figure 1B). No patient relapsed at the last follow-up on July 31, 2023. The estimated 1-year progression-free survival (PFS) and overall survival (OS) both stood at 90% (Figure 1C). Conclusion Short-term blinatumomab as a bridging therapy for adult patients with low-burden B-ALL transitioning to ASCT demonstrates comparable efficacy to standard dosing regarding disease control and survival outcomes.

BackgroundThe use of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA) has long been considered the standard regimen for preventing chemotherapy-induced nausea and vomiting (CINV) prior to hematopoietic stem cell transplantation (HSCT). However, their therapeutic outcomes have been unsatisfactory. NEPA, an oral formulation combining the neurokinin-1 receptor antagonist netupitant and the 5HT3RA palonosetron, has received regulatory approval for the management of highly and moderately emetogenic chemotherapy. This study aims to compare the efficacy of NEPA with that of 5HT3RA alone in preventing CINV among patients undergoing multiday conditioning chemotherapy prior to HSCT.Patients and methodsWe conducted a retrospective analysis of patients who underwent HSCT between September 2019 and September 2022. Efficacy outcomes were assessed based on the rates of patients achieving complete response (CR: no emesis and no use of rescue medication), complete control (CC: CR without significant nausea), no vomiting, and no significant nausea.ResultsThe NEPA group consisted of 106 patients, while the 5HT3RA group included 107 patients. The NEPA group exhibited significantly higher rates of CR compared to the 5HT3RA group during the overall phase (71.7% vs. 32.7%, P<0.001), acute phase (78.3% vs. 43.0%, P<0.001), and delayed phase (84.9% vs. 58.9%, P<0.001). Similarly, rates of CC, no vomiting, and no significant nausea were significantly better in the NEPA group across all phases (P<0.001).ConclusionNEPA demonstrated superior efficacy compared to 5HT3RA in preventing CINV during all phases of multiday conditioning regimens among patients undergoing HSCT.

Aim: A registered study to investigate the efficacy and safety of bendamustine plus melphalan conditioning for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) (ChiCTR2100047782). Method: Bendamustine and melphalan were given to patients at the dose of 150 mg/m 2 on Days -5 and -4 and 70 mg/m 2 on Days -3 and -2, respectively. Progression-free survival (PFS) and overall survival (OS) were used to assess the efficacy and adverse events were used to assess the safety of the conditioning regimen. Results: A total of 80 patients were included in our study. Of them, 45 patients achieved complete response (CR); 7 patients achieved very good partial response (VGPR), and 28 patients achieved partial response (PR) before ASCT. With a median follow-up period of 16 months, the overall PFS rate was 91%, and the overall OS rate was 95%. Patients with CR pre-transplantation were all in CR until the last follow-up; two patients with VGPR pre-transplantation relapsed and one of them died; four patients with PR pre-transplantation relapsed and one of them died. The median time to neutrophile and platelet engraftment were 11 (9-13) and 13 (10-18) days. Three patients experienced sepsis during ASCT. Vomiting occurred in 45 (57.2%) patients; diarrhea occurred in 27 (34.2%) patients, transaminase elevation was observed in 18 (22.3%) patients; mucositis was found in 16 (18.8%) patients. All these adverse events were grade 1-2, and no grade 3-4 adverse events were observed. Conclusion: Bendamustine plus melphalan regimen is promising for ASCT in MM patients, and the long-term efficacy and safety remain to be investigated.

BackgroundThe prognosis of patients with peripheral T-cell (PTCL) or lymphoblastic T-cell lymphoma (T-LBL) remains poor under current conditioning regimens before receiving autologous stem cell transplantation (ASCT).MethodsPatients with PTCL or T-LBL were enrolled to receive ASCT using the conditioning regimen of chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Positron emission tomography-computed tomography (PET/CT) was used to evaluate the response to ASCT. Overall survival (OS) and progression-free survival (PFS) were employed to assess the patient outcome, and adverse events were used to assess the regimen’s safety. The survival curve was estimated via the Kaplan-Meier method.ResultsTwenty-five PTCL and 11 T-LBL patients were recruited. The median time to neutrophile and platelet engraftments was 10 days (8–13 days) and 13 days (9–31 days), respectively. The 3-year PFS and OS were 81.3 ± 7.2% and 88.5 ± 5.4% for all patients; 92.0 ± 5.4% and 81.2 ± 8.8% for PTCL patients; and both 81.8 ± 11.6% for T-LBL patients, respectively. The 3-year PFS and OS were both 92.9 ± 4.9% for patients with complete response (CR) but 50.0 ± 17.7% and 75.0 ± 15.3% for patients with non-CR, respectively. Infection was the most common non-hematological toxicity, and all toxicities were mild and controllable.ConclusionsChiCGB was a potentially effective and well-tolerated conditioning regimen to improve the prognosis of patients with aggressive T-cell lymphoma. Future randomized controlled trials are needed to assess ChiCGB as a conditioning regimen for ASCT.

The treatment of patients with acute myeloid leukemia (AML) who are intolerable to intensive chemotherapy remains to be further explored. Recent studies have shown that venetoclax combined with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) may have a good effect on these patients. Given the lack of a comprehensive analysis of the efficacy and safety of such treatment, the aim of this review was to assess the efficacy and safety of venetoclax plus HMAs or LDAC for untreated AML patients who are ineligible for intensive chemotherapy. A systematic literature review was conducted in the PubMed, Embase, and Cochrane databases up to April 30, 2021. A total of four clinical trials including 440 patients were eligible for this meta-analysis. The pooled complete remission (CR) and complete remission plus complete remission with incomplete blood count recovery (CR/CRi) rates were 0.40 (95

To the Editor: As of July 4, 2021, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has affected >0.18 billion individuals and caused >3.9 million deaths worldwide.[1] Currently, the only method to radically overcome this pandemic is extensive vaccination. However, the clinical trials assessing most vaccines against SARS-CoV-2 have excluded patients with hematological tumors. Thus, only limited data are available in hematological tumor patients with respect to vaccine safety, tolerability, and effectiveness. The lack of such data in hematologic tumor patients leads to hesitation towards the immunization approach and undermines current policies regarding vaccination. Currently, six vaccines against SARS-CoV-2 are available in China. However, vaccination agencies in most communities in China do not allow or recommend vaccination for hematological tumor patients. Therefore, acquiring the safety data of SARS-CoV-2 vaccines in such patients is imperative for individual choice and public health policies. Chronic myeloid leukemia (CML) is a chronic hematological tumor. CML patients have a life expectancy close to that of healthy individuals. Hitherto, the safety of SARS-CoV-2 vaccination in CML patients has been reported only in a few cases.[2,3] Therefore, we performed a multicenter cross-sectional survey in CML patients who had undergone SARS-CoV-2 vaccination. Online questionnaires were dispatched to CML patients by physicians in nine medical centers through social media. Each questionnaire included an informed consent form and 17 anonymous questions addressing demographics, comorbidities, CML status and treatments, and SARS-CoV-2 vaccination status and adverse events (AEs), as well as contact information. The questionnaires were filled by CML patients voluntarily. Missed or unclear data were verified by contacting the patients through telephone calls, e-mail, or WeChat. AEs were graded according to the following scale: Grade 1 (mild, not interfering with activity); Grade 2 (moderate, interfering with activity); Grade 3 (severe, preventing daily activity); Grade 4 (potentially life-threatening, emergency department visit, or hospital admission). Logistic regression analysis was performed to examine the associations of clinical parameters (gender, age, disease course, Tyrosine Kinase Inhibitor (TKI) types, comorbidities, and BCR-ABL1 level) with vaccination-related factors (vaccines type and doses) and AEs. Variables with P < 0.05 were considered significant. Analyses were performed with SPSS version 22.0 (SPSS Inc., Chicago, IL, USA). The study was approved by the Ethics Committee of West China Hospital, Sichuan University. We finally recruited 335 CML patients across 29 provinces in China who were vaccinated against SARS-CoV-2. All these respondents completed the online questionnaire, and 268 also participated in telephone interviews. Fifty-one respondents had interviews though e-mails or social media channels such as WeChat. Sixteen respondents declined interviews besides the online questionnaire. The median time between vaccination and questionnaire submission was seven (range: 1–172) days. The characteristics of the respondents are listed in [Supplementary Table 1, https://links.lww.com/CM9/A863]. All respondents were in the chronic phase (CP). Among them, 89.3% (299/335) achieved major molecular response or deeper molecular response, and 80.5% (270/335) of respondents received the inactivated vaccine. Totally 75.5% (253/335) of respondents received one dose of the vaccine, and the remaining individuals received two doses. A total of 64 (19.1%) respondents reported AEs after vaccination. The most common (11.0%, 37/335) AEs were injection-site pain. The most common systemic AEs were fatigue (3.0%, 10/335), sleepiness (2.1%, 7/335), and flu-like symptoms (2.1%, 7/335). Other AEs included fever, headache, diarrhea, dizziness, hypogeusia, knee pain, lumbago, and gout attack. The median duration of AEs was 1 day (ranging from 1 to 7 days). Two respondents presented Grade 2 flu-like symptoms. AEs in all the remaining respondents were Grade 1, and no Grade 3 to 4 AEs were reported. The detected AEs are summarized in [Figure 1]. Interestingly, the AEs of vaccination were not significantly associated with vaccine brand, TKI types, other vaccine characteristics, or patient features, except for younger age (P = 0.001) [Supplementary Table 1, https://links.lww.com/CM9/A863], which may indicate a stronger immune response in young people.Figure 1: Local and systemic effects reported after SARS-CoV-2 vaccination in patients with CML: (A) Proportions of participants reporting no toxicity or toxicity. (B) Breakdown of specific local and systemic side effects. Symptoms were graded according to the following scale: Grade 1 (mild, not interfering with activity); Grade 2 (moderate, interfering with activity); Grade 3 (severe, preventing daily activity); Grade 4 (potentially life-threatening, emergency department visit or hospital admission). Others include headache, diarrhea, dizziness, hypogeusia, knee pain, lumbago, and gout attack. CML: Chronic myeloid leukemia; SARS-CoV-2: Severe acute respiratory syndrome coronavirus-2.Pimpinelli et al[2] assessed the safety and immunogenicity of the BNT162b2 vaccine (Pfizer–BioNTech) against SARS-CoV-2 in 20 CML patients. The findings showed that the vaccine was safe in CML patients, and no vaccine-related Grade 3 to 4 AEs occurred. Harrington et al[3] drew a similar conclusion in a small cohort of 16 CML patients administered a single dose of the BNT162b2 vaccine. However, both studies had the limitation of a small sample size. The current study is a large multicenter study assessing the safety of SARS-CoV-2 vaccines in CML patients. Moreover, this is a rare report examining five available SARS-CoV-2 vaccines in CML patients. The incidence of AEs in CML patients in this study was not higher than that of healthy individuals reported in previous phase 2 or 3 trials of the inactivated vaccine in China (range: 19.0–48.3%).[4,5] More importantly, no serious AEs were reported. Nevertheless, the present study had several limitations. First, the “Survivorship bias” might characterize this questionnaire survey; in other words, deceased patients would be excluded from the survey by default. However, none of the previous trials of these vaccines[4,5] have reported vaccination-related death, which indicates a minimal possibility of “Survivorship bias”. Second, the number of CML patients vaccinated with recombinant adenovirus vaccine or recombinant protein subunit vaccine was small. Third, CML-related data, including the levels of the fusion gene BCR-ABL1 before and after vaccination, were not collected in this study. In summary, the current findings suggested that the SARS-CoV-2 vaccines described here are safe for chronic phase-chronic myeloid leukemia (CP-CML) patients. Additional studies with data about CML-related AEs and the levels of protective antibodies are needed to further evaluate the safety and effectiveness of SARS-CoV-2 vaccination in CML patients. Acknowledgements Authors would like to thank the patients who volunteered to participate in this study. Conflicts of interest None.

Objective:To explore clinical efficacy of imatinib mesylate (IM) in treatment of patients with Langerhans cell histiocytosis (LCH), and to conduct a review of relevant literature.Methods:From April to July 2019, a total of 3 patients with LCH who were admitted to West China Hospital of Sichuan University and treated with IM were selected as research subjects, and these patients were numbered as patients 1 to 3 in order of admission. The diagnosis of patients were mainly according to results of histopathological and immunohistochemical examination. Patients were treated with IM-based regimens and followed until February 28, 2022. Clinical manifestations and process of diagnosis and treatment of these 3 patients were analyzed retrospectively. Using " Langerhans cell histiocytosis" " imatinib mesylate" and " imatinib" as China and English keywords, to retrieve literature related to IM for treatment of patients with LCH, from China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform, PubMed database, Embase database and Ovid Medline database by computer. Retrieval time was from databases inception to February 28, 2022. A review of relevant literature was conducted to summarize clinical characteristics and response of IM in patients with LCH. The procedure of this study was in line with the requirements of the World Medical Association Declaration of Helsinki revised in 2013. Results:① Results of medical history were as follows. Patient 1, a 63 years old woman, was admitted due to " polyuria and polydipsia for 5 years, and headache accompanied by pain in the right thigh for 4 months" . Patient 2, a 61 years old woman, was admitted due to " right maxillary ulcer for 1 month" , and examination results of local hospital suggested LCH. Patient 3, a 38 years old man, was admitted due to " persistent and intractable right gingival ulcer" . The patient was diagnosed with LCH involving the right gingiva and lung, and received treatments in other hospital, but his condition was poorly controlled. ② Results of related laboratory examinations were as follows. Patient 1 underwent examination of biopsy histopathology, immunohistochemistry, brain MRI, whole-body PET/CT, radionuclide whole-body bone imaging and pituitary function test etc. After admission, the examination results suggested multiple systems LCH (MS-LCH) and hypopituitarism with this patient. Patient 2 underwent biopsy pathological and immunohistochemical examinations in local hospital, which showed LCH, and the BRAF V600E gene mutation test was negative. Patient 3 underwent immunohistochemical examination, chest CT and brain MRI, which suggested MS-LCH with him. ③ Results of treatment were as follows. For patient 1, the symptoms were not relieved after 3 courses of AVP (cytarabine+ vinoresin+ prednisone) regimen, then treatment regimen changed to AVP plus IM (100 mg/d). At the end of the 8 courses of AVP regimen, the pain gradually subsided, so treatment continued with IM alone. Until the end of follow-up, the patient′s urine output gradually decreased, and no pain or other symptoms occurred. Patient 2 started IM (100 mg/d) treatment after diagnosis as single system LCH (SS-LCH), and right maxillary ulcer healed after 3 months. Treatment continued with IM until the end of follow-up, there was no disease recurrence or progression. Patient 3 recurred in situ when consulted our hospital, after 6 months of IM (100 mg/d) and recombinant human interferon alpha-2b (3 million IU, once a week) treatment, the oral and lung lesions were better than before. After the next 4 months of treatment, the patient developed headache and a lump at his fronto-parietal bone. LCH ectopic recurrence was considered. Therefore, the treatment was changed to IM 200 mg/d and recombinant human interferon α-2b (3 million IU, once a week). After 2 months treatment, the patient′s headache was slightly relieved and the lump was smaller than before. The treatment was continued until the end of follow-up, the patient′s oral lesions healed, the lump dissipated, lung lesions remained unchanged and still had headache. ④ Results of literature review were as follows. Among 13 patients reported in 7 relevant literatures, one patient had SS-LCH involvement, while the others had MS-LCH. Five patients were initially treated with IM, of which 4 patients were ineffective. Eight patients were treated with vinblastine, etoposide, prednisone and other chemotherapy or radiotherapy before IM, and all of them responded to IM in varying degrees. Conclusions:IM was found to be effective in patients with LCH who were failure with first-line treatment or in combination with other chemotherapeutic drugs.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is a high-risk disease subtype with a dismal prognosis. Inhibiting BCR-ABL kinase alone is insufficient to eradicate Ph+ALL clones, and alternative BCR-ABL-dependent and -independent pathways need to be targeted as an effective strategy. Our study revealed that the combination of dasatinib and interferon-α showed synergistic activity against Ph+ALL, inducing mitochondrial dysfunction and causing necrosis-like cell lysis. Mechanistic studies showed that the induced cell death was caspase-3-independent. Canonical necroptosis signals, such as RIP1 and MLKL, were not activated; instead, the pyroptosis executor Gasdermin D was upregulated expression and activated. The expression levels of extracellular ATP and IL-1β were also upregulated, both of which are markers of pyroptotic cell death. In a murine Ph+ALL model, the dual drug treatment prolonged the survival of tumor-bearing mice. More importantly, we incorporated the dual drugs to maintenance therapy in 39 patients who were unfit for allogeneic stem cell transplantation (allo-HSCT). The median follow-up was 28.5 months, the 4-year disease-free survival and overall survival rates were 52.2% and 65.2%, respectively. Our data suggest that the combination of dasatinib and interferon-α has potential synergistic activity against Ph+ALL and shows promise as a maintenance therapy for Ph+ALL patients who are unfit for allo-HSCT.

Abstract Primary adrenal lymphoma (PAL) is a sporadic malignant disease characterized by a high level of invasiveness and a poor prognosis. Symptoms are atypical, making it difficult to obtain an accurate early diagnosis. Some patients may have fever, night sweats, weight loss, lumbar and abdominal pain, and adrenal insufficiency. Certain clinical signs and biochemical characteristics can help clinicians make an early and rapid diagnosis to prevent a delay in treatment. Here, we report a case of a female patient with unilateral PAL and low back pain. After rapid diagnosis, R-CHOP chemotherapy combined with autologous peripheral stem cell transplantation was administered; the patient's condition improved significantly, and her prognosis was good. There was no recurrence during a follow-up period of more than two years.