Abstract
T-cell replete Haploidentical stem cell transplantation (Haplo-SCT) with Post-transplant cyclophosphamide (PT-Cy) is an emerging therapeutic option for patients with advanced relapsed or refractory lymphoma. The feasibility of this platform is supported by several retrospective studies showing a toxicity profile that is improved relative to umbilical cord blood and mismatched unrelated donor (UD) transplant and comparable to matched unrelated donor transplant. In particular, cumulative incidence of chronic graft-versus-host disease (GVHD) is reduced after Haplo-SCT relative to UD and matched related donor (MRD) transplant thanks to PT-Cy employed as GVHD prophylaxis. This achievement, together with a similar incidence of acute GVHD and disease relapse, results in a promising advantage of Haplo-SCT in terms of relapse-free/GVHD free survival. Unmet needs of the Haplo-SCT platform are represented by the persistence of a not negligible rate of non-relapse mortality, especially due to infections and disease relapse. Future efforts are warranted in order to reduce life-threatening infections and to employ Halo-SCT with PT-Cy as a platform to build new immunotherapeutic strategies.
Highlights
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) represents a potential curative option for patients with refractory or relapsed lymphomas thanks to the immune-mediated graft-versus-lymphoma (GVL) effect
Long-term results of these reports are quite promising: 3-/4-year overall survival (OS) ranges between 54% and 77%, progression free survival (PFS) is 38–66%, non-relapse mortality (NRM) rate is acceptable ranging between 4% and 26%, that is in line with that reported after matched related donor (MRD) or MUD transplants
In a recent publication from a multicenter retrospective analysis we have shown that choice of a younger haploidentical donor results in lower chance of acute GVHD (aGVHD) and reduced NRM, while a sibling should be preferable to a parent donor in terms of relapse incidence and PFS and a father donor is better than the mother both for OS and PFS [53]
Summary
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) represents a potential curative option for patients with refractory or relapsed lymphomas thanks to the immune-mediated graft-versus-lymphoma (GVL) effect. The existence of a GVL effect is supported first by the evidence of a reduced incidence of relapse for patients with Hodgkin (HL) and non-Hodgkin (NHL) lymphoma after Allo-HSCT (ranging between 6% and 29%) relative to autologous transplant (ranging between 35% and 69%) [1,2,3,4,5]. The development of new drugs for relapsed/refractory lymphomas has challenged the role of allogeneic transplant in this setting. Despite the high overall response rates (ORR) achieved with new drugs, long-term outcome is still a matter of debate: only 9 out of 102 patients were apparently cured at 5-years by brentuximab in relapsed/refractory (R/R) HL [17]; median duration of response was 16.5 months for
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