T-Cell–Replete HLA-Haploidentical Hematopoietic Transplantation for Hematologic Malignancies Using Post-Transplantation Cyclophosphamide Results in Outcomes Equivalent to Those of Contemporaneous HLA-Matched Related and Unrelated Donor Transplantation

Bashey, Asad; Zhang, Xu; Sizemore, Connie A.; Manion, Karen; Brown, Stacey; Holland, H. Kent; Morris, Lawrence E.; Solomon, Scott R.

doi:10.1200/jco.2012.44.3523

Cited by 455 publications

(417 citation statements)

References 22 publications

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“…We retrospectively compared outcomes of 53 consecutive Haplo-post-HCT-CY to 117 MRD and 101 MUD transplants contemporaneously performed at our center. 36 The three groups were comparable for patient and disease characteristics except that Haplo-post-HCT-CY patients were more likely to receive BM grafts and a RIC regimen. All patients received treatment primarily in the outpatient setting with inpatient admission for complications.…”

Section: Screen Recipient For Antibodies Targeting Mismatched Donor Hmentioning

confidence: 92%

T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor

Bashey

Solomon

2014

Bone Marrow Transplant

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Availability of an HLA-identical sibling (MRD) or suitably matched unrelated donor (MUD) has historically been a limiting factor in the application of allogeneic hematopoietic transplantation. Although almost all patients have an HLA-haploidentical family donor, prior attempts at transplantation from such donors using T-cell replete grafts and conventional immunosuppression were associated with unacceptable rates of GVHD, and when stringent ex vivo T-cell depletion was used to control GVHD, rates of graft rejection and post-transplant infections were prohibitive. The recent approach to HLA-haploidentical donor transplantation developed in Baltimore that uses T-cell replete grafts and post-transplant CY (Haplo-post-HCT-CY) to control post-transplant allo-reactivity appears to have overcome many of the obstacles historically associated with haploidentical donor transplantation. In particular, TRM rates of o10% are usual and rapid reconstitution of immunity leads to a low rate of post-transplant infections and no post-tranplant lymphoproliferative disorders (PTLD), consistent with the hypothesis that post-transplant CY selectively depletes proliferating alloreactive T cells responsible for GVHD and graft rejection while preserving resting memory T cells essential for post-transplant immunologic recovery. In parallel trials using similar non-myeloablative conditioning regimens, Haplo-post-HCT-CY produced similar overall survival to double umbilical cord blood transplantation(DUCBT) in adult patients (62% vs 54%), with low rates of TRM (7% vs 24%), severe acute GVHD (0% vs 21%) and chronic GVHD (13% vs 25%). Furthermore, recent non-randomized comparisons adjusted for risk factors show that Haplo-post-HCT-CY achieve at least equivalent outcomes to conventional MRD and MUD transplants. Although most experience has been obtained using BM, emerging data suggest that a G-CSF mobilized PBSC graft can also safely be used for Haplo-post-HCT-CY. Haplo-post-HCT-CY also avoids the graft acquisition costs of DUCBT and MUDs and the cost of cell selection associated with T-depleted grafts. Although randomized comparisons will be forthcoming, Haplo-post-HCT-CY can already be considered a valid standard-of-care in patients who lack conventional donors thus extending the availability of allogeneic transplants to almost all patients. This donor source may also challenge the routine preference for a MUD in patients lacking an MRD.

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Section: Screen Recipient For Antibodies Targeting Mismatched Donor Hmentioning

confidence: 92%

T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor

Bashey

Solomon

2014

Bone Marrow Transplant

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“…1 HLA-haploidentical donor transplantation (HIDT) using a T-cell-replete graft with posttransplant cyclophosphamide has emerged as an alternative graft source for patients lacking a matched-related (MRD) or matchedunrelated (MUD) donor. [2][3][4][5] The use of HIDT with post-transplant cyclophosphamide has been shown to yield low rates of transplant-related mortality, adequate disease control, robust immune reconstitution and overall survival (OS) similar to that seen with optimally MUD transplantations. 2,6 Relapse remains the main cause of treatment failure after HCT with~30-40% of patients relapse with their original malignancy.…”

Section: Introductionmentioning

confidence: 99%

Post-relapse survival after haploidentical transplantation vs matched-related or matched-unrelated hematopoietic cell transplantation

Solh

Zhang

Connor

et al. 2016

Bone Marrow Transplant

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Relapse remains a major cause of mortality among patients receiving allogeneic hematopoietic cell transplantation (HCT). The impact of donor type on post-relapse survival (PRS) has not been widely examined. We compared the survival outcomes for patients relapsing after haploidentical donor transplantation (HIDT) using post-transplant cyclophosphamide with those relapsing after matched-related donor transplantation (MRDT) or matched-unrelated donor transplantation (MUDT) at our institution. Two hundred and thirty-seven consecutive HCT recipients with relapse occurring after HIDT (N = 48), MUDT (N = 87) and MRDT (N = 102) were included in this analysis. Median age was 49 years (19-77 years) and the median time to relapse was 156 days (12-2465) after HCT. HIDT recipients had similar median time to relapse (5.8 vs 4.8 vs 5.5 months, P = 0.638) compared with MUDT and MRDT, respectively. One-year PRS was worse among HIDT recipients compared with MRDT and MUDT (17% vs 46% vs 40%, P o 0.05). In a multivariate analysis, time to relapse ( o3 vs 43 months post transplant), no use of donor lymphocyte infusion (DLI) following relapse, higher Dana Farber disease risk index and HCT comorbidity index scores at the time of transplant and delayed platelet engraftment post transplant were all predictive of worse PRS. This analysis shows that 1-year PRS is inferior among HIDT when compared with MRDT or MUDT. Lower use of DLI after HIDT may have contributed to this inferior survival. INTRODUCTIONAllogeneic hematopoietic cell transplantation (HCT) is considered to be a curative modality for many patients with high-risk hematologic malignancies. Transplantation using a matchedrelated sibling if available leads to improved outcomes when compared with other graft sources. 1 HLA-haploidentical donor transplantation (HIDT) using a T-cell-replete graft with posttransplant cyclophosphamide has emerged as an alternative graft source for patients lacking a matched-related (MRD) or matchedunrelated (MUD) donor. [2][3][4][5] The use of HIDT with post-transplant cyclophosphamide has been shown to yield low rates of transplant-related mortality, adequate disease control, robust immune reconstitution and overall survival (OS) similar to that seen with optimally MUD transplantations. 2,6 Relapse remains the main cause of treatment failure after HCT with~30-40% of patients relapse with their original malignancy. 7 Outcomes after relapse after HCT remain poor with a high early mortality and only a small percentage of patients achieving a long-term second remission and prolonged OS. The effect of graft donor source at the time of transplantation on post-relapse survival (PRS) has not been well established. In a recent CIBMTR (Center for International Blood and Marrow Transplantation Research) analysis, patients with relapsed acute myelogeneous leukemia after mismatchedunrelated or double cord transplantation had a worse PRS than recipients of a matched sibling or matched-unrelated HCT. 8 The available treatment options for relapsed patients include i...

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“…For MSD, MUD and haploSCT cases, the 2-year cumulative incidence of NRM was 13%, 16% and respectively 7%, while relapse was similar (34% vs 34% vs 33%). The 2-year disease-free survival was 53%, 52% and 60% [21]. The transplant unit from MD Anderson Cancer Center in the United States have analyzed the outcomes of 227 patients treated with fludarabine 120-160 mg/m 2 , melphalan 100-140 mg/m 2 and thiotepa 5-10 mg/kg, for the haploidentical cases.…”

Section: Discussionmentioning

confidence: 99%

First Successful Haploidentical Stem Cell Transplantation in Romania

Tănase

Tomuleasa

Marculescu

et al. 2016

Romanian Journal of Internal Medicine

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Hematopoietic stem cell transplantation is an established treatment for many malignant and non-malignant haematological disorders. In the current case report, we describe the first haploidentical stem cell transplantation, used for the first time in Romania, the case of a 33 year-old young woman diagnosed with Hodgkin's lymphoma that has underwent a haploSCT after she relapsed from several chemotherapy regimens, as well as after an autologous stem cell transplantation. This success represents a prèmiere in Romanian clinical hematology, being the first case of a haploSCT in Romania, as well as in South-Eastern Europe.

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T-Cell–Replete HLA-Haploidentical Hematopoietic Transplantation for Hematologic Malignancies Using Post-Transplantation Cyclophosphamide Results in Outcomes Equivalent to Those of Contemporaneous HLA-Matched Related and Unrelated Donor Transplantation

Cited by 455 publications

References 22 publications

T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor

T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor

Post-relapse survival after haploidentical transplantation vs matched-related or matched-unrelated hematopoietic cell transplantation

First Successful Haploidentical Stem Cell Transplantation in Romania

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