Uniform graft-versus-host disease prophylaxis with posttransplant cyclophosphamide, sirolimus, and mycophenolate mofetil following hematopoietic stem cell transplantation from haploidentical, matched sibling and unrelated donors

Montoro, Juan; Piñana, José Luís; Hernández‐Boluda, Juan Carlos; Hernani, Rafael; Lorenzo, Ignacio; Pérez, Ariadna; Guerreiro, Manuel; Balaguer‐Roselló, Aitana; Sanz, Guillermo; Carretero, Carlos; Albert, Eliseo; Navarro, David; Sanz, Miguel Á.; Solano, Carlos; Sanz, Jaime

doi:10.1038/s41409-020-0921-6

Cited by 39 publications

(31 citation statements)

References 40 publications

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“…This was mainly due to the absence of graft failure and a lower infectious mortality rate. Comparable NRM rates with PTCy-Sir-MMF have been recently been reported in the haploidentical setting, 10 and across all types of allo-HSCT in a larger series of our group, 9 and with PTCy-Sir in recipients of MSD and MUD allo-HSCT. 37 Interestingly, the incidence and As previously described, 9 we observed a higher rate of late-onset hepatic SOS in the PTCy-Sir-MMF cohort.…”

Section: Discussionsupporting

confidence: 72%

“…2,4,5 However, sirolimus (Sir) with MMF has recently emerged as an alternative option to calcineurin inhibitor (CNI)-containing approaches, since it has an apparently more favorable toxicity profile [6][7][8] with encouraging results. 9,10 The aim of the present study was to retrospectively compare the clinical outcomes of adults with acute leukemia or myelodysplastic syndrome (MDS) undergoing myeloablative allo-HSCT from matched sibling donors (MSD) or unrelated donors at three institutions with two different strategies for GVHD prophylaxis, ex vivo TCD by CD34+ selection and unmanipulated grafts with PTCy-Sir-MMF. The PTCy-Sir-MMF platform was used at two institutions in Valencia (HUPLF and HCU), while the ex vivo CD34 + selected TCD transplants were carried out at HUVH in Barcelona.…”

Section: Introductionmentioning

confidence: 99%

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Ex vivo T‐cell depletion vs post‐transplant cyclophosphamide, sirolimus, and mycophenolate mofetil as graft‐vs‐host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

Montoro

Roldán

Piñana

et al. 2020

European J of Haematology

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Objective To compare the efficacy and safety of CD34+ selected ex vivo T‐cell depletion (TCD) vs post‐transplant cyclophosphamide, sirolimus, and mycophenolate mofetil (PTCy‐Sir‐MMF) as graft‐vs‐host disease (GVHD) prophylaxis. Methods We retrospectively included patients who underwent allogeneic hematopoietic stem cell transplantation (allo‐HSCT) with either TCD (n = 38) or PTCy‐Sir‐MMF (n = 91). Results Cumulative incidence of neutrophil and platelet recovery was 92% vs 99% (P = .06) and 89% vs 97% (P = .3) in TCD and PTCy‐Sir‐MMF, respectively. Cumulative incidences of aGHVD grade II‐IV, III‐IV, and moderate to severe cGVHD were 11% vs 19% (P = .2), 3% vs 2% (P = .9), and 3% vs 36% (P < .001) in TCD and PTCy‐Sir‐MMF, respectively. The 2‐year non‐relapse mortality, relapse, disease‐free and overall survival were 25% vs 8% (P = .01), 20% vs 16% (P = .2), 55% vs 76% (P = .004), 57% vs 83% (P = .004) for TCD and PTCy‐Sir‐MMF, respectively. Cumulative incidence of cytomegalovirus and Epstein‐Barr infection requiring therapy was 76% vs 40% (P < .001) and 32% vs 0% (P < .001) in TCD and PTCy‐Sir‐MMF, respectively. PTCy‐Sir‐MMF platform showed faster T‐cell reconstitution. Conclusions PTCy‐Sir‐MMF provides better survival outcomes but is associated with higher risk of cGVHD compared to TCD.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Ex vivo T‐cell depletion vs post‐transplant cyclophosphamide, sirolimus, and mycophenolate mofetil as graft‐vs‐host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

Montoro

Roldán

Piñana

et al. 2020

European J of Haematology

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“…The PT-Cy alone or in combination with other immunosuppressants was considered as one of the mainstay of GVHD prophylaxis strategies in various hematological malignancies (1,2,(17)(18)(19). In a retrospective analysis from Acute Leukemia Working Party of the EBMT (AWLP-EBMT) with 423 patients transplanted in MSD and MUD setting, the diagnosis of ALL (vs. AML, p = 0.008) and PBSCs as graft (vs. BM, p = 0.01) were associated with higher incidence of II-IV aGVHD or ext cGVHD respectively.…”

Section: Discussionmentioning

confidence: 99%

Post-transplantation Cyclophosphamide, Tacrolimus and Low-Dose ATG as GVHD Prophylaxis for Allogeneic Peripheral Stem Cell Transplantation for Adult Patients With Lymphoid Malignancies: A Single Arm Phase II Study

et al. 2021

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The PT-Cy was considered as one of the mainstay protocol for graft verus host disease (GVHD) prophylaxis. Recent study demonstrated that PT-Cy combined with other immunosuppressants could further reduce the incidence of GVHD and improve the GVHD and relapse free survival (GRFS). In this prospective phase II study, we evaluated the effect of a new GVHD prophylaxis consist of PT-Cy combined with tacrolimus and low dose anti-thymoglobulin (ATG). A total of 23 patients were enrolled including 20 patients with acute lymphoblastic leukemia (ALL) and three patients with T cell lymphoma. The median age was 29 years (range, 16~58 years). Patients with HLA-matched related donor (MSD, n=7) received PT-Cy combined with tacrolimus, while patients with HLA matched unrelated (MUD, n = 2) or haplo-identical (Haplo, n = 14) donor received additional ATG at 2.5 mg/kg on day 15 or day 22 after engraftment of neutrophils. As to the acute GVHD (aGVHD), only three patients developed grade I (n = 1) or grade II (n = 2) aGVHD with 100-day incidence of all aGVHD and II-IV aGVHD at 13.0 ± 5.1% and 9.1 ± 6.1% respectively. Only two patients had mild and one had moderate chronic GVHD (cGVHD), with 1-year incidence of cGVHD and moderate/severe cGVHD at 15.2 ± 8.7% and 4.6 ± 4.4% respectively. A high incidence of CMV reactivation was documented (14/16 with MUD/Haplo donor and 2/7 with MSD) with only 1 CMV disease documented. There were two EBV reactivation without post-transplantation lymphoproliferative disease (PTLD) documented. With a median follow-up of 303 days (range, 75~700 days), three patients relapsed leading to 1-year cumulative incidence of relapse (CIR) at 12.8 ± 9.2%. Only one patient died of CMV pneumonia on day 91 with both 100-day and 1-year non-relapse mortality (NRM) at 4.6 ± 4.4%. The 1-year overall survival (OS), event-free survival (EFS) and GRFS were 95.5 ± 4.4%, 82.6 ± 9.5%, and 68.0 ± 11.3% respectively. Based on Simon's stage II design, our primary data showed that the PT-Cy+tacrolimus ± ATG protocol was promising in preventing aGVHD and cGVHD, which may translate into low NRM without increased CIR. Further clinical trial with large number of patients should be warranted. This trial was registered at www.clinicaltrials.gov as #NCT 04118075.

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“…Selection of a haploidentical donor did not vary between periods and it has previously been described in detail [12]. Briefly, a haploidentical family donor was selected according to the following considerations…”

Section: Donor Selection and Source Of Stem Cellsmentioning

confidence: 99%

Sirolimus versus cyclosporine in haploidentical stem cell transplantation with posttransplant cyclophosphamide and mycophenolate mofetil as graft‐versus‐host disease prophylaxis

Hernani

Piñana

Pérez

et al. 2021

eJHaem

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Sirolimus has emerged as an alternative to calcineurin inhibitors-based (CNI) graftversus-host disease (GVHD) prophylaxis. This retrospective study compares the outcome of 133 consecutive adult patients with haematological malignancies undergoing haploidentical stem cell transplantation with posttransplant cyclophosphamide (PTCy) and mycophenolate mofetil (MMF), combined with cyclosporine A (PTCy-CsA-MMF, n = 67) or sirolimus (PTCy-Sir-MMF, n = 66) as GVHD prophylaxis strategy. The median follow-up was 48 (range 22-83) and 13 (range 3-33) months, respectively.PTCy-CsA-MMF was associated in multivariate analyses with a higher risk of acute kidney injury (HR 2.1, 95% CI, 1.21-3.57, p = .008) and thrombotic microangiopathy (HR 12.5, 95% CI, 1.66-93.5, p = .014), whereas PTCy-Sir-MMF was associated with a higher risk of hepatic sinusoidal obstruction syndrome (SOS) (HR 10.8, 95% CI, 1.52-77, p = .018), especially late-onset forms, which totally resolved and none of the patients needed discontinuation of sirolimus. Two SOS-related deaths were detected, both in the PTCy-CsA-MMF subgroup. Both GVHD prophylaxis strategies were otherwise comparable in terms of engraftment, GVHD incidence and survival.

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Uniform graft-versus-host disease prophylaxis with posttransplant cyclophosphamide, sirolimus, and mycophenolate mofetil following hematopoietic stem cell transplantation from haploidentical, matched sibling and unrelated donors

Cited by 39 publications

References 40 publications

Ex vivo T‐cell depletion vs post‐transplant cyclophosphamide, sirolimus, and mycophenolate mofetil as graft‐vs‐host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

Ex vivo T‐cell depletion vs post‐transplant cyclophosphamide, sirolimus, and mycophenolate mofetil as graft‐vs‐host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

Post-transplantation Cyclophosphamide, Tacrolimus and Low-Dose ATG as GVHD Prophylaxis for Allogeneic Peripheral Stem Cell Transplantation for Adult Patients With Lymphoid Malignancies: A Single Arm Phase II Study

Sirolimus versus cyclosporine in haploidentical stem cell transplantation with posttransplant cyclophosphamide and mycophenolate mofetil as graft‐versus‐host disease prophylaxis

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