Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia

Ciurea, Stefan O.; Zhang, Mei Jie; Bacigalupo, Andrea; Bashey, Asad; Appelbaum, Frederick R.; Aljitawi, Omar S.; Armand, Philippe; Antin, Joseph H.; Chen, Junfang; Devine, Steven M.; Fowler, Daniel H.; Luznik, Leo; Nakamura, Ryotaro; O’Donnell, Paul V.; Perales, Miguel Angel; Pingali, Sai Ravi; Porter, David; Riches, Marcie L.; Ringdén, Olle; Rocha, Vanderson; Vij, Ravi; Weisdorf, Daniel J.; Champlin, Richard E.; Horowitz, Mary M.; Fuchs, Ephraim J.; Eapen, Mary

doi:10.1182/blood-2015-04-639831

Cited by 600 publications

(515 citation statements)

References 36 publications

(43 reference statements)

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“…28 Finally, a CIBMTR registry analysis reported 192 AML patients who underwent PT-Cy Haplo-SCT, with similar outcome but lower chronic GVHD compared with matched unrelated donor Allo-HSCT. 29 Taken together, these results suggest that PT-Cy Haplo-SCT is feasible and effective in high-risk patients with AML or MDS who lack HLA-matched donor. We suppose that the anticipated high incidence of relapse after Haplo-SCT may be due to the advanced characteristics of patients rather than the procedure itself.…”

Section: Discussionmentioning

confidence: 74%

T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes

Devillier

Bramanti

Fürst

et al. 2015

Bone Marrow Transplant

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Unmanipulated haploidentical transplantation (Haplo-SCT) using post-transplantation cyclophosphamide (PT-Cy) represents an alternative for patients with high-risk diseases lacking HLA-identical donor. Although it provides low incidences of GVHD, the efficacy of Haplo-SCT is still questioned, especially for patients with myeloid malignancies. Thus, we analyzed 60 consecutive patients with refractory (n = 30) or high-risk CR (n = 30) AML or myelodysplastic syndromes (MDSs) who underwent PT-Cy Haplo-SCT. The median age was 57 years (22-73 years), hematopoietic cell transplantation comorbidity index was ⩾ 3 in 38 patients (63%) and Haplo-SCT was the second allogeneic transplantation for 10 patients (17%). Although most of patients received PBSC as graft source (n = 48, 80%), we found low incidences of grade 3-4 acute (2%) and severe chronic GVHD (4%). Among patients with high-risk CR diseases, 1-year non-relapse mortality, cumulative incidence of relapse, progression-free and overall survivals were 20%, 32%, 47% and 62%, respectively. In patients with refractory disease, corresponding results were 34%, 35%, 32% and 37%, respectively. We conclude that PT-Cy Haplo-SCT could provide promising anti-leukemic effect even in the setting of very advanced diseases. Thus, it represents a viable alternative for high-risk AML/MDS patients without HLA-identical donor.

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Section: Discussionmentioning

confidence: 74%

T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes

Devillier

Bramanti

Fürst

et al. 2015

Bone Marrow Transplant

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“…The issue is noteworthy since the reproducibility, the acceptable toxicity and the ease of finding a donor within the appropriate timing is conducting to an increasing use of haplo-HSCT with PT-Cy overall, 1 even challenging the use of matched unrelated donors in particular situations. 2,3 CMV infection is known to be responsible for substantial morbidity and mortality following allogeneic transplantation; 4,5 most findings suggest that CMV serostatus significantly affects patient survival especially in situations of sustained immunosuppression (myeloablative conditioning, unrelated donor, use of T-cell depletion), whereas the same question is still open in the setting of haplo-HSCT with PT-Cy.…”

mentioning

confidence: 99%

The patient’s CMV serological status affects clinical outcome after T-cell replete haplo-HSCT and post-transplant cyclophosphamide

Crocchiolo

Castagna

Fürst

et al. 2016

Bone Marrow Transplant

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“…For example, persons with AML receiving an HLA-haplotype-matched transplant and posttransplant cyclophosphamide have a significantly lower incidence of chronic GvHD than recipients of HLA-matched unrelated transplants, but no increase in leukaemia relapse risk. 6 Similarly, a lower incidence of chronic GvHD with no increase in leukaemia relapse risk was reported in a cohort of subjects receiving a HLA-haplotype-matched transplant with post-transplant cyclophosphamide compared with recipients of HLA-identical sibling transplants for lymphoma. 7 One possible explanation why decreasing the proportion of persons diagnosed with chronic GvHD did not result in more leukaemia relapses is the direct antileukaemia activity of cyclophosphamide given post transplant.…”

mentioning

confidence: 86%

Is there really a specific graft-versus-leukaemia effect?

Gale

Fuchs

2016

Bone Marrow Transplant

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Allotransplants in persons with leukaemia are associated with a decreased leukaemia relapse risk compared with transplants from genetically-identical twins. There is considerable controversy whether this operational anti-leukaemia effect, sometimes termed graft-versus-leukaemia (GvL), is immunologically specific to the leukaemia or results from donor immune cells reacting to disparate recipient HLA and non-HLA histocompatibility antigens on leukaemia cells or both. If so, this effect is better seen as an aspect of GvHD. These theoretical distinctions are presented schematically in Figure 1.We previously studied leukaemia relapse rates in 2264 persons with acute and chronic leukaemias receiving T-cell replete or -depleted transplants from diverse donors including HLA-matched siblings and who were diagnosed or not as having acute and/or chronic GvHD. 1 We included a comparator cohort of recipients of T-cell replete transplants from genetically-identical twins. Our analyses, reproduced in Figure 2, identified the highest leukaemia relapse rate in recipients of T-cell replete transplants from genetically-identical twins and the lowest in recipients of T-cell replete allotransplants diagnosed with acute and chronic GvHD. Recipients of T-cell-depleted allotransplants not diagnosed with acute or chronic GvHD had a significantly higher risk of leukaemia relapse than similar recipients of T-cell replete allotransplants also not diagnosed with acute or chronic GvHD. On the basis of these data we postulated two anti-leukaemia effects in the setting of allotransplants: (1) an anti-leukaemia effect associated with a diagnosis of acute or chronic GvHD (or both), but especially chronic GvHD and (2) a separate anti-leukaemia effect in persons not diagnosed with acute or chronic GvHD likely mediated by T cells (or by cells removed by diverse techniques and labelled as T-cell depletion in our study). We could not, of course, distinguish between an allogeneic leukaemia-specific immune response and a non-leukaemia-specific alloimmune effect in persons with no diagnosis of acute or chronic GvHD. The latter possibility is of considerable concern given the difficulty in accurate diagnosis of acute GvHD (for example, Pidala et al. 2 ). However, there is less discordance in the diagnosis of chronic GvHD that was associated with the lowest risk of leukaemia relapse. 3 These data did not allow us to determine whether there might be an allogeneic nonspecific anti-leukaemia effect distinct from chronic GvHD. For example, an immune reaction to disparate HLA-or non-HLA histocompatibility antigens might release cytokines such as interferons or interleukins to which leukaemia cells might be more sensitive than normal cells. Such an effect would be operationally, but not immunologically, leukaemia-specific. However, a person with leukaemia and his/her physician might not care if the effect was operationally or immunologically specific provided the risk of leukaemia relapse was less.There is recent considerable interest and data in persons with l...

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Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia

Cited by 600 publications

References 36 publications

T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes

T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes

The patient’s CMV serological status affects clinical outcome after T-cell replete haplo-HSCT and post-transplant cyclophosphamide

Is there really a specific graft-versus-leukaemia effect?

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