Long-term outcome of HLA-haploidentical hematopoietic SCT without in vitro T-cell depletion for adult severe aplastic anemia after modified conditioning and supportive therapy

Gao, Li; Li, Yongsheng; Zhang, Y; Chen, X; Zhang, C; Liu, Y; Kong, Peiyan; Wang, Q; Su, Yi; Wang, C; S, Wang; Li, B; Sun, Aihua; Du, Xin; Zeng, Dongfeng; Li, J; Liu, H; Zhang, X

doi:10.1038/bmt.2013.224

Cited by 62 publications

(58 citation statements)

References 31 publications

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“…In these small series, rejection has been between 6% and 25%, acute GVHD between 12% and 30%, chronic GVHD between 20% and 40%, and overall survival between 62.5% and 84.6% [42–44]. In the largest and most recently published cohort from China [37], 101 patients prospectively received haploidentical BMT from June 2012 through October 2015.…”

Section: Discussionmentioning

confidence: 99%

Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia

DeZern

Zahurak

Symons

et al. 2017

Biology of Blood and Marrow Transplantation

109

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Severe aplastic anemia (SAA) is a life-threatening hematopoietic stem cell disorder that is treated with bone marrow transplantation (BMT) or immunosuppressive therapy (IST). The management of patients with refractory SAA after IST is a major challenge. Alternative donor BMT is the best chance for cure in refractory SAA, but morbidity and mortality from graft failure and complications of graft-versus-host disease (GVHD) have limited enthusiasm for this approach. Here, we employed post-transplantation high-dose cyclophosphamide in an effort to safely expand the donor pool in 16 consecutive patients with refractory SAA who did not have a matched sibling donor. Between July 2011 and August 2016, 16 patients underwent allogeneic (allo) BMT for refractory SAA from 13 haploidentical donors and 3 unrelated donors. The nonmyeloablative conditioning regimen consisted of antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation. Post-transplantation cyclophosphamide 50 mg/kg/day i.v. on days +3 and +4 was administered for GVHD prophylaxis. Additionally, patients received mycophenolate mofetil on days +5 through 35 and tacrolimus from day +5 through 1 year. The median age of the patients at the time of transplantation was 30 (range, 11 to 69) years. The median time to neutrophil recovery over 1000 × 103/mm3 for 3 consecutive days was 19 (range, 16 to 27) days, to red cell engraftment was 25 (range, 2 to 58) days, and to last platelet transfusion to keep platelets counts over 50 × 103/mm3 was 27.5 (range, 22 to 108) days. Graft failure, primary or secondary, was not seen in any of the patients. All 16 patients are alive, transfusion independent, and without evidence of clonality. The median follow-up is 21 (range, 3 to 64) months. Two patients had grade 1 or 2 skin-only acute GVHD. These same 2 also had mild chronic GVHD of the skin/mouth requiring systemic steroids. One of these GVHD patients was able to come off all IST by 15 months and the other by 17 months. All other patients stopped IST at 1 year. Nonmyeloablative alloBMT using post-transplantation cyclophosphamide allowed for safe expansion of the donor pool to include HLA-haploidentical donors. This approach appears promising in refractory SAA patients. Importantly, engraftment was 100%, pre-existing clonal disease was eradicated, and the risk of GVHD was low.

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Section: Discussionmentioning

confidence: 99%

Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia

DeZern

Zahurak

Symons

et al. 2017

Biology of Blood and Marrow Transplantation

109

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“…Currently, the kinetics of IR in patients with SAA after haplo-SCT have only been described for a relatively small number of cases. 13,14,[26][27][28] Koh et al 26 depicted CD3 + , CD4 + and CD56 + cell reconstitution after haplo-SCT using CD3 or CD3/CD19 depletion conditioning in four SAA patients. Their data showed that three of the four patients achieved CD3 + cell counts of 4400 cells/μL and CD4 + cell counts of 4150 cells/μL on day 180.…”

Section: Discussionmentioning

confidence: 99%

Immune reconstitution in patients with acquired severe aplastic anemia after haploidentical stem cell transplantation

et al. 2017

Bone Marrow Transplant

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Immune recovery (IR) after haploidentical stem cell transplantation (haplo-SCT) in severe aplastic anemia (SAA) patients remains relatively unknown. In this study, we examined immune cell subset counts and immunoglobulins in 81 SAA patients from day 30 to day 365 after haplo-SCT. Simultaneously, we determined which factors influence IR and analyzed the effects of immune cell subsets on transplant outcomes. We found that: (i) The reconstitution of different immune cell subsets occurred at different rates after haplo-SCT. Monocytes were the first to recover, followed by CD8 T and CD19 B cells, and finally CD4 T cells. (ii) In the multivariate analysis, lower recipient age, female gender, high mononuclear cell counts in the graft and absence of CMV reactivation were associated with improved IR after transplant. (iii) A CD4/CD8 ratio less than 0.567 on day 30 post transplantation was associated with higher overall survival after haplo-SCT in SAA patients. In conclusion, SAA patients showed a faster recovery of monocytes and CD8 T cells after haplo-SCT, whereas the recovery of the CD4 T-cell subset was delayed. Our results may provide insight into methods for better predicting and modulating IR of SAA patients and subsequently improving outcomes after transplantation.

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“…MMF (7.5 mg/kg twice per day) was started on day þ1 and was discontinued on day þ90. Acute GVHD (aGVHD) and chronic GVHD (cGVHD) were treated as previously described by Gao L. et al [16,17].…”

Section: Graft-versus-host Disease Prophylaxis and Managementmentioning

confidence: 99%

Effects of Priming with Recombinant Human Granulocyte Colony–Stimulating Factor on Conditioning Regimen for High-Risk Acute Myeloid Leukemia Patients Undergoing Human Leukocyte Antigen–Haploidentical Hematopoietic Stem Cell Transplantation: A Multicenter Randomized Controlled Study in Southwest China

Gao

Qin

Chen

et al. 2014

Biology of Blood and Marrow Transplantation

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HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective and immediate treatment for high-risk acute myeloid leukemia (HR-AML) patients lacking matched donors. Relapse remains the leading cause of death for HR-AML patients after haplo-HSCT. Accordingly, the prevention of relapse remains a challenge in the treatment of HR-AML. In a multicenter randomized controlled trial in southwestern China, 178 HR-AML patients received haplo-HSCT with conditioning regimens involving recombinant human granulocyte colony-stimulating factor (rhG-CSF) or non-rhG-CSF. The cumulative incidences of relapse and graft-versus-host disease (GVHD), 2-year leukemia-free survival (LFS), and overall survival (OS) were evaluated. HR-AML patients who underwent the priming conditioning regimen with rhG-CSF had a lower relapse rate than those who were treated with non-rhG-CSF (38.2%; 95% confidence interval [CI], 28.1% to 48.3% versus 60.7%, 95% CI, 50.5% to 70.8%; P < .01). The cumulative incidences of acute GVHD, chronic GVHD, transplantation-related toxicity, and infectious complications appeared to be equivalent. In total, 53 patients in the rhG-CSF-priming group and 31 patients in the non-rhG-CSF-priming group were still alive at the median follow-up time of 42 months (range, 24 to 80 months). The 2-year probabilities of LFS and OS in the rhG-CSF-priming and non-rhG-CSF-priming groups were 55.1% (95% CI, 44.7% to 65.4%) versus 32.6% (95% CI, 22.8% to 42.3%) (P < .01) and 59.6% (95% CI, 49.4% to 69.7%) versus 34.8% (95% CI, 24.9% to 44.7%) (P < .01), respectively. Multivariate analyses indicated that the 2-year probability of LFS of patients who achieved complete remission (CR) before transplantation was better than that of patients who did not achieve CR. The 2-year probability of LFS of patients with no M4/M5/M6 subtype was better than that of patients with the M4/M5/M6 subtype in the G-CSF-priming group (67.4%; 95% CI, 53.8% to 80.9% versus 41.9%; 95% CI, 27.1% to 56.6%; P < .05). This study suggests that the rhG-CSF-priming conditioning regimen is an acceptable choice for HR-AML patients, especially for the patients with no M4/M5/M6 subtype who achieved CR before transplantation.

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Long-term outcome of HLA-haploidentical hematopoietic SCT without in vitro T-cell depletion for adult severe aplastic anemia after modified conditioning and supportive therapy

Cited by 62 publications

References 31 publications

Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia

Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia

Immune reconstitution in patients with acquired severe aplastic anemia after haploidentical stem cell transplantation

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