Nonmyeloablative HLA-Haploidentical Bone Marrow Transplantation with High-Dose Posttransplantation Cyclophosphamide: Effect of HLA Disparity on Outcome

Kasamon, Yvette L.; Luznik, Leo; Leffell, Mary S.; Kowalski, Jeanne; Tsai, Hua Ling; Bolaños-Meade, Javier; Morris, Lawrence E.; Crilley, Pamela; O’Donnell, Paul V.; Rossiter, Nancy; Huff, Carol Ann; Brodsky, Robert A.; Matsui, William; Swinnen, Lode J.; Borrello, Ivan; Powell, Jonathan D.; Ambinder, Richard F.; Jones, Richard J.; Fuchs, Ephraim J.

doi:10.1016/j.bbmt.2009.11.011

Cited by 247 publications

(237 citation statements)

References 38 publications

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“…20 Unlike with prior approaches to HaploD transplantation, greater degrees of HLA-disparity between HaploD and recipient for the non-shared haplotype were not associated with a higher rate of acute GVHD or NRM but a trend to a lower relapse risk an improved EFS. 21 Although donor BM has been the graft source in most cases, some investigators have substituted G-CSF-mobilized PBSC as the graft source in selected patients without observing an increase in rates of GVHD or NRM (O'Donnell, P-personal communication and Bashey, unpublished data) although no formal comparisons have been reported.…”

Section: Use Of Post-transplant Cy To Selectively Control Allo-reactimentioning

confidence: 99%

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: Use Of Post-transplant Cy To Selectively Control Allo-reactimentioning

confidence: 99%

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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“…12,13 So far, few data are available on this approach for the treatment of patients relapsing after autologous and allogeneic HSCT. 12,14 However, given the poor results to be expected with DLI and conventional HSCT2 from sibling and MUD, haploidentical HSCT2 according to this protocol was performed at two German transplant centres as treatment of choice for all patients with AL relapse after HSCT1. The rapid availability of an HLA partially matched related donor as compared with an alternative MUD and a possible advantage of a stronger GvL effect 15,16 in the haploidentical setting as compared with both HLA-matched sibling donors and MUD were regarded as possible advantages of this strategy.…”

Section: Introductionmentioning

confidence: 99%

Second haematopoietic SCT using HLA-haploidentical donors in patients with relapse of acute leukaemia after a first allogeneic transplantation

Tischer

Engel

Fritsch

et al. 2014

Bone Marrow Transplant

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Haploidentical haematopoietic SCT (HSCT) using T-cell-replete grafts and post-transplant high-dose CY has found increasing acceptance. Our purpose was to evaluate the feasibility and outcome of this strategy as second HSCT incorporating donor change for acute leukaemia relapse after a first allogeneic transplantation. The courses of 20 consecutive adults (median age 37 years, 12 male) with AML (n = 14), ALL (n = 5) and acute bi-phenotypic leukaemia (n = 1) were analysed retrospectively. Conditioning consisted of fludarabine, CY and either melphalan or TBI or tresosulfan+/ -etoposide. Engraftment was achieved in 17 (85%), and a second remission was induced in 15 patients (75%) on day +30. The rate of grade II-IV acute GvHD was 35%, while chronic GvHD occurred in five patients. Most commonly observed grade III-IV toxicities were mucositis (30%), hyperbilirubinemia (20%), elevation of transaminases (20%) and creatinine (20%), while invasive fungal infection affected 30%. One-year non-relapse mortality (NRM) was 36%. At a median follow-up of 17 months, estimated 1-year OS was 45%, and 1-year relapse-free survival was 33%. This strategy was feasible and allowed for successful engraftment with a moderate rate of toxicity. Early outcome and NRM are at least comparable with results after a second HSCT from HLA-matched donors without donor change at HSCT2.

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“…The Peking group reported the feasibility of transplantation using granulocyte colony-stimulating factor-mobilized bone marrow and peripheral blood stem cells from the same haploidentical donor with myeloablative conditioning consisting of cytosine arabinoside, busulfan, cyclophosphamide, semustine, and ATG, followed by GVHD prophylaxis consisting of CsA, sMTX, and MMF [93]. The Johns Hopkins group developed unmanipulated haploidentical bone marrow transplantation with high-dose posttransplantation cyclophosphamide as sole GVHD prophylaxis [94]. Table 3 shows a summary of pretransplant conditioning and GVHD prophylaxis regimens used for HLA-haploidentical donor transplantation in Japan.…”

Section: Gvhd Prophylaxis Regimens For Hla-haploidentical Donor Transmentioning

confidence: 99%

Prophylactic and therapeutic treatment of graft-versus-host disease in Japan

Murata

2015

Int J Hematol

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Nonmyeloablative HLA-Haploidentical Bone Marrow Transplantation with High-Dose Posttransplantation Cyclophosphamide: Effect of HLA Disparity on Outcome

Cited by 247 publications

References 38 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

Second haematopoietic SCT using HLA-haploidentical donors in patients with relapse of acute leukaemia after a first allogeneic transplantation

Prophylactic and therapeutic treatment of graft-versus-host disease in Japan

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