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Background: Pure red cell aplasia (PRCA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with ABO major incompatibility is characterized by transfusion dependent anemia. No standard treatment existed for PRCA following allo-HSCT yet., Study Design and Methods: We conducted a retrospective study, and reported our experience with the use of avatrombopag and lower dose rituximab to treat five patients with PRCA subsequent to major ABO-incompatible allo-HSCT., Results: Five cases of PRCA were identified from 72 patients who underwent allo-HSCT with major or bidirectional ABO mismatch. Cumulative incidence at Day +60 was 6.9% (5/72) at our center. All donor and recipient blood groups were A +  and O + , respectively. In the first three cases we reported, patients received erythropoietin, plasma exchange, and donor lymphocyte infusion, but none of them had any effect. After 4 weeks of treatment with low dose rituximab (100 mg/week) combined with avatrombopag (40 mg/day), favorable outcomes were obtained. According to the aforementioned experience, Cases 4 and 5 were administered low-dose rituximab and avatrombopag in 3 months after transplantation, and erythroid response was observed on 3 weeks after treatment. Our patients tolerated low-dose rituximab and avatrombopag well and experienced rapid efficacy, with a median duration of 3 weeks. Furthermore, no severe infection or thrombocytosis necessitated a dose adjustment., Conclusion: Low-dose rituximab and avatrombopag may be an effective treatment for patients with PRCA after major ABO-incompatible allo-HSCT. The patients should be treated at least 90 days post transplantation if conventional erythropoietin therapy fails., (© 2024 AABB.)

Myeloid-derived suppressor cells (MDSC) are powerful immunomodulatory cells that play an important role in infectious and inflammatory disorders, but the correlation between graft MDSC amount and early transplant outcomes remains unknown in allogeneic hematopoietic stem cell transplantation. We collected data from 91 patients with acute leukemia undergoing haploidentical allogeneic hematopoietic stem cell transplantation. The grafts were analyzed in terms of CD34+ cells, CD3+ T cells and subpopulation, and MDSC (HLA-DR -/low CD33 + CD16 - ) by flow cytometry. The cutoff value of the MDSC proportion in the graft on the receiver operating curve was 8.89%, with a sensitivity of 0.833 and specificity of 0.852. Day +100 cumulative incidences of II-IV and III-IV acute graft-versus-host disease (aGVHD) in the low MDSC group were 73.5% and 38.8%, respectively, and that in the high MDSC group were 5.3% and 0%, with a significant difference in incidences of II-IV and III-IV aGVHD ( P <0.001). The overall survival, relapse-free survival, and GVHD-relapse-free survival (GRFS) at 1 year were 66.3% versus 80.5% ( P =0.043), 71.6% versus 71.7% ( P =0.248), and 22.1% versus 62.8% ( P <0.001), respectively. No significant difference in the cumulative incidence of relapse between the 2 groups was observed. Multivariate analysis revealed that higher MDSC proportions were associated with a lower risk of II-IV aGVHD. Graft MDSC proportion exceeding 8.89% was significantly associated with higher overall survival and GRFS. The prophylaxis of antithymocyte globulin+post-transplant cyclophosphamide and higher MDSC proportion in the graft were favorable factors for improving GRFS. In conclusion, graft MDSC proportion may be a significant predictor of aGVHD., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Post-transplantation cyclophosphamide (PTCy) can reduce the incidence of graft versus host disease (GVHD) and this intervention is often applied on adults with hematologic malignancy. However, the high relapse rate hinders the development of the intervention and data of PTCy used on children with hematologic malignancy remains limited. In order to overcome issue of high relapse rate in PTCy treatment, we used fludarabine (Flu), enhanced dose of cytarabine (Ara-C, 9 g/m 2 ), busulfan (Bu), Cy, anti-thymocyte globulin (ATG) combined with PTCy for an intensified conditioning regimen., Methods: A total of 22 children with acute leukemia received intensified PTCy conditioning regimen (PTCy intensified group). We matched with 18 children who received modified Bu-Cy and ATG conditioning regimen in the same period (ATG group)., Results: The two-year cumulative incidences of grade II-IV acute GVHD was significantly lower in PTCy intensified group (13.6 ± 7.7% vs 38.9 ± 11.5%, P  = 0.048). Two-year GVHD-free relapse free survival (GRFS) in PTCy seems to be better among the increment group despite not being significant (63.3 ± 10.3% vs 35.4 ± 11.9%, P  = 0.092). The positive rate of minimal residual disease after transplantation was significantly lower than that before transplantation (20.0% vs 2.5%, P  = 0.029)., Conclusion: In conclusion, ATG and PTCy combined with Flu-based increased intensity conditioning regimen is effective for acute leukemia in children. It could reduce GVHD rate significantly and potentially improve GRFS.

A single injection of 12 mg pegfilgrastim was used to mobilize peripheral blood progenitor cells (PBPCs) from healthy donors in some studies. The purpose of this study was to determine if 6 mg of pegfilgrastim was effective and safe for mobilizing CD34+ cells in donors for allogeneic hematopoietic stem cell transplantation. We conducted a retrospective case-matched design. A single dosage of 6 mg pegfilgrastim was used to mobilize PBPCs from 60 healthy donors. Granulocyte colony-stimulating factor (G-CSF, 10 μg/kg) was administered daily to the matched donors. Leukapheresis was scheduled to commence on day 4 of the mobilization regimen. The median yielded CD34+ cell in the pegfilgrastim group was higher than those in the G-CSF group, at 5.06 × 10 6 /kg recipient weight. The 73.3% of donors mobilized with pegfilgrastim yielded >4 × 10 6 cells/kg CD34+ cells in a single apheresis procedure when compared to the 33.3% of donors mobilized with G-CSF (P < 0.001). The myeloid-derived suppressor cells (MDSC) proportion in the pegfilgrastim group was significantly higher than that in the G-CSF group (P < 0.001). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was higher in the G-CSF group than that in the pegfilgrastim group (26.7% vs. 11.7%), without statistical difference. In comparison to the G-CSF group, the pegfilgrastim group had a reduced median pain intensity numerical rating scale score (1 vs. 2). A single 6 mg dosage of pegfilgrastim is effective and safe for allogeneic PBPCs collection from healthy donors. Pegfilgrastim may decrease the incidence of aGVHD by boosting MDSCs, which need further investigation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Relapse and graft-versus-host disease (GVHD) are the important complications influencing mortality for patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). GVHD prophylaxis based on post-transplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) is widely used in haploidentical HSCT (haplo-HSCT)., Objective: We developed a modified intensified conditioning regimen including fludarabine (Flu) and investigated the effect of ATG-PTCy combination on transplant outcomes in high-risk AML and MDS compared with those patients who received only ATG as GVHD prophylaxis., Methods: A total of 80 patients with high-risk AML and MDS were divided into two groups and assigned to one-to-one pairing., Results: The modified ATG-PTCy group had more infused mononuclear cells, CD34-positive cells and CD3-positive cells than those in the ATG group (P < 0.05). The amount of platelet transfusion was higher in the ATG group than the modified ATG-PTCy group [2 (range, 1-6) U vs 2 (range, 1-5) U, P = 0.005]. The median of platelet recovery was better in the modified ATG-PTCy group than in the ATG group (12 days vs 13 days,P = 0.041). The infection rates of bacteria, fungi and virus at 100 days after transplantation were similar in both groups. Compared with the ATG group, individuals who received the modified ATG-PTCy regimen had higher 2-year GVHD- and relapse-free survival(GRFS) [60.0% (95%CI, 44.9-75.1%) vs 34.8% (95%CI, 19.9-49.7%), P = 0.028]; lower 180-day incidence of II-IV acute GVHD (aGVHD) [15.0% (95%CI, 4.0-26.0%) vs 39.8% (95%CI, 23.9-55.7%), P = 0.029]; lower 1-year incidence of moderate to severe chronic GVHD (cGVHD) [2.9% (95%CI, 2.0-3.8%) vs 19.6% (95%CI, 5.3-33.9%), P = 0.039]; and without an increase in the 2-year cumulative incidence of relapse (CIR) [19.5% (95%CI, 6.6-32.4%) vs 30.4% (95%CI, 15.3-45.5%), P = 0.291]., Conclusions: High-dose stem cells can promote blood cell implantation. The modified ATG-PTCy combination was associated with decreased risk of aGVHD and cGVHD, no increased risk of recurrence, and improved GRFS. It represents an effective strategy for high risk AML and MDS., Competing Interests: Declaration of Competing Interest All authors reviewed the manuscript. The authors have declared no conflicts of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Chemotherapy-induced nausea and vomiting (CINV) is common in patients with lymphoma and multiple myeloma (MM) receiving high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Despite a standard triple antiemetic regimen of a neurokinin-1 (NK1) receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone is recommended, how to control the protracted CINV in ASCT setting remains an intractable problem. Here, we retrospectively analyze CINV data of 100 patients who received either SEAM (semustine, etoposide, cytarabine, melphalan) or MEL140-200 (high-dose melphalan) before ASCT, evaluate the efficacy and safety of multiple-day administration of fosaprepitant combined with tropisetron and olanzapine (FTO), and compare the results to those of patients who received a standard regimen of aprepitant, tropisetron, and dexamethasone (ATD). The overall rate of complete response (CR), defined as no emesis and no rescue therapy, is 70% in the FTO group compared to 36% in the ATD group. Although CR rates are comparable in the acute phase between the two groups, significantly more patients treated by FTO achieve CR in the delayed phase than those treated by ATD (74% vs. 38%, p < 0.001). Moreover, FTO treatment significantly reduced the percentage of patients who are unable to eat, as well as the requirement for rescue medications. Both regimens are well tolerated and most adverse events (AEs) were generally mild and transient. In conclusion, the antiemetic strategy containing multiple-day administration of fosaprepitant is safe and effective for preventing CINV in lymphoma and MM patients, particularly in the delayed phase., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There is no consensus on the optimal secondary antifungal prophylaxis (SAP) regimen in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). The purpose of this study was to evaluate the efficacy and safety of posaconazole oral suspension as secondary prophylaxis of invasive fungal disease (IFD) for allo-HSCT patients., Methods: We retrospectively reviewed clinical data from prior IFD patients who received posaconazole oral suspension as systemic antifungal prophylaxis between June 2016 and January 2021 and have a follow-up period of 1 year after HSCT. The clinical outcomes of patients with a prior history of IFD (n = 30) and those without (n = 93) were compared., Results: The 1-year cumulative incidence of prophylaxis failure was 58.3% in the group with prior history of IFD and 41.6% in the group without a prior history of IFD (p = 0.459). The cumulative incidence of proven, probable or possible IFD within 1 year after allo-HSCT was 23.1% in the group with prior history of IFD and 14.1% in the group without prior history of IFD (p = 0.230). There was no significant difference between the cumulative incidence of proven or probable IFD within 1-year after allo-HSCT in the group with a prior history of IFD and the group without (p = 0.807). Multivariate logistic regression revealed cytomegalovirus disease as risk factor for post-transplantation IFD occurrence in posaconazole oral suspension prophylaxis. There was not a significant difference in overall survival between the patients with IFD history and those without (P = 0.559)., Conclusions: Our study support that allo-HSCT recipients with a prior history of IFD and normal GI absorption can choose posaconazole oral suspension as a safe and effective SAP option., (© 2022. The Author(s).)

In order to investigate the efficacy of lenalidomide, bortezomib and dexamethasone (VRD) induction chemotherapy regimen combined with tandem autologous stem cell transplantation (ASCT) in treating multi-hit multiple myeloma (MM), we analyzed 252 cases of newly diagnosed MM treated with the bortezomib-containing induction chemotherapy from June 2016 to June 2019. According to the fluorescence in situ hybridization (FISH) results on diagnosis, the patients were divided into multi-hit MM group (47 cases), single-hit MM group (81 cases), and standard-risk group (124 cases). Our analysis showed that R-ISS stageⅢ in transplantation group and R-ISS stageⅢ, multi-hit and VGPR or above was not achieved at the fourth cycle of chemotherapy in non-transplantation group were independent factors for poor prognosis by univariate and multivariate analyses. Moreover, the overall response rate (ORR) of VRD induction chemotherapy group was significantly higher than that of the non-VRD group in the single-hit and multi-hit groups (P = 0.021, P = 0.032); In terms of ASCT, tandem-ASCT can significantly improve the 2-year PFS (77.8 ± 3.9 %) and OS (83.3 ± 5.6 %) of multi-hit MM (P = 0.024, P = 0.037), while single-ASCT only has a limited effect on PFS (61.5 ± 3.0 %) and OS (71.9 ± 4.5 %) (P = 0.115, P = 0.155)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)