Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies

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Introduction:We evaluated the combination of ATG and PTCy for GVHD prophylaxis in matched and mismatched unrelated PBSCTs for high-risk hematological malignancies. Methods:We treated 102 patients with reduced intensity conditioning (RIC) with fludarabine, busulfan, and TBI 200 cGy. GVHD prophylaxis included rabbit ATG (thymoglobulin at total dose of 4.5 mg/kg divided over days −3 to −1), PTCy (50 mg/ kg/day on day +3 and on day +4), and cyclosporine. Clinical and outcome data were collected retrospectively.Results: Among 102 patients, 76 patients received 10/10 MUD transplants and 26 patients received 9/10 mismatched transplants. The median age was 59 years. At a median follow-up of 15 months (range 0.6 to −33 months), the 1-year OS in MUD and MMUD cohort was 75% and 50%, respectively (P = 0.027). The corresponding oneyear PFS was 67% and 35%, respectively (P = 0.0024). The incidence of grade 3-4 acute GVHD was 11.8% in MUD and 3.8% in MMUD group, and that of NIH stage moderate/severe chronic GVHD in the 2 groups was 10.5% and 7.6%, respectively.Cytomegalovirus (CMV) reactivation was seen in 49% patients. The cumulative incidence of relapse was 21.1% in the MUD group and 42.3% in the MMUD group. Conclusion:Our experience shows that PTCy and ATG can be combined for GVHD prophylaxis in matched unrelated donor PBSCTs with low rates of Gr3-4 acute GVHD and chronic GVHD, and acceptable relapse rates. K E Y W O R D S ATG, graft-versus-host disease, post-transplant cyclophosphamide 1 | INTRODUC TI ON Post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis in the setting of matched related (MRD), matched and mismatched unrelated (MUD and MMUD), and haplo-identical (HI) transplants has been associated with low rates of acute and chronic GVHD. 1-3 Similarly, ATG has been used extensively for GVHD prophylaxis for MUD transplants with beneficial effects in reducing acute and chronic GVHD. 4,5 There is little published data on combining ATG with PTCy for GVHD prophylaxis in MUD peripheral blood stem cell | 487 PREM Et al.

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confidence: 99%

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants

Prem

Atenafu

Al‐Shaibani

et al. 2019

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“…Supportive care and prophylaxis have been previously reported in detail. [29][30][31] Main information is summarized in the supplementary data.…”

Section: Conditioning Regimen Graft-versus-host Disease Prophylaximentioning

confidence: 99%

“…As has been reported in previous publications with larger number of patients, the novel combination of ATG and PTCY combined with CsA provides good control of GVHD rates when peripheral blood stem cell grafts are used. [29][30][31] PTCy decreases the risk of GVHD and graft rejection by targeting and inducing cell apoptosis of allo-reactive T cells, preserving nondividing hematopoietic stem cells. 26 The use of ATG in conditioning regimens decreases rates of acute and chronic GVHD and graft rejection by depleting donor and recipient T cells, and without increasing relapse rates.…”

Section: Outcomementioning

confidence: 99%

“…27,28 The combination of both PTCy and ATG in the setting of allo-HSCT using peripheral blood as source of graft is safe and results in low rates of GVHD. [29][30][31] The aim of the present study is to identify potential risk factors and outcome of patients with MF who underwent allo-HSCT with this protocol since October 2015 to December 2018. The present study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee at the Princess Margaret Cancer Centre, Toronto, Canada.…”

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confidence: 99%

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Reduced‐intensity conditioning allogeneic transplant with dual T‐cell depletion in myelofibrosis

Salas

Lam

Law

et al. 2019

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Background There remains a significant mortality in recipients with MF who undergo allogeneic stem cell transplant (allo‐HSCT). The combination of antithymocyte globulin (ATG) and post‐transplant cyclophosphamide (PTCy) provides good control of graft‐versus‐host disease (GVHD) when peripheral blood stem cell grafts are used. Methods We report the outcome of 37 recipients with myelofibrosis who underwent reduced‐intensity conditioning (RIC) allo‐HSCT with ATG and PTCy. Median follow‐up was 16.4 months. Results Nine (24.3%) recipients received 10/10 MRD grafts, 17 (45.9%) 10/10 MUD grafts, 4 (10.8%) 9/10 MUD grafts, and 7 (18.9%) haploidentical donor grafts. Six (16.3%) patients had graft failure. The cumulative incidence of grade II‐IV and grade III‐IV aGVHD at day +100 and moderate/severe chronic GVHD at 1 year was as follows: 13.5%, 5.4%, and 17%. There were no deaths secondary to GVHD. One‐year overall survival (OS), relapse‐free survival (RFS), non‐relapse mortality (NRM), and GVHD‐free/RFS (GRFS) were respectively 74.4%, 71.3%, 23%, and 43.3%. Those recipients who had worse KPS ≤ 80% had worse OS and RFS. Conclusion RIC allo‐HSCT with ATG and PTCy results in high OS and RFS in patients with myelofibrosis and absence of mortality secondary to GVHD. Further investigations are required to reduce NRM and graft failure rates.

“…Supportive care and infectious prophylaxis was previously described in detail. 23,24 Daily G-CSF 300 mcg subcutaneously was administrated until neutrophils were >1.5 × 10 6 /L from day +7.…”

Section: Conditioning Regimen Post-transplant Immunosuppression Amentioning

confidence: 99%

Impact of CD34+ cell dose on reduced intensity conditioning regimen haploidentical hematopoietic stem cell transplantation

Salas

Atenafu

Bautista

et al. 2019

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Objectives Haploidentical hematopoietic stem cell transplant (haplo‐SCT) has been associated with higher rates of graft rejection, and a higher dose of CD34+ cell dose is frequently requested. We aim to explore the impact of CD34+ cell dose in peripheral blood stem cell (PBSC) grafts using reduced intensity conditioning (RIC) in haplo‐SCT. Methods Sixty‐eight consecutive haplo‐SCT in adult patients were included. Graft‐vs‐host disease (GVHD) prophylaxis consisted on ATG, PTCy, and CsA. The cohort was divided in two groups using CD34+ dose of ≥ 9 × 106 CD34+/Kg as cutoff point. Median follow‐up was 8.9 months. Results Median cell dose infused was 9.32 × 106 CD34+/Kg. Forty (58.8%) recipients received grafts with CD34+ cells ≥9 × 106/kg. The infusion ≥ 9 × 106 CD34+/Kg cell dose had a negative impact in overall survival (P = .03) after adjusting for age at transplant. The cumulative incidence of acute GVHD and graft failure were not significantly influenced per CD34+ cell dose. Only four recipients had grade III aGVHD, and all of them received grafts with a CD34+ cell dose ≥ 9 × 106. Conclusion In RIC haplo‐SCT, recipients may not benefit from PBSC grafts with a CD34+/kg cell dose higher than 9 × 106 cells/kg, as it can have an adverse impact in post‐transplant outcome.