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The outcomes of an historic comparison of 117 consecutive, high-risk, acute leukemia patients undergoing hematopoietic stem cell transplantation (HSCT) from HLA-mismatched/haploidentical donors (HID, n = 81) or HLA-identical sibling donors (ISD, n = 36) without the use of in vitro T cell depletion (TCD), between the period of January 2005 and April 2009 were compared. Full engraftment was achieved in 98% of patients in the HID group and 97% in the ISD group. The cumulative incidences of grades II–IV acute graft-versus-host disease (aGVHD) in the HID and ISD cohorts were 49% and 24%, respectively (P = .014) with a relative risk (RR) of 2.99 (1.25-7.21) (P = .014). The incidence of chronic GVHD (cGVHD) did not differ significantly between the 2 cohorts. The 2-year cumulative incidence of relapse was significantly lower in HID (26%) than in ISD patients (49%) (P = .008). The 2-year cumulative incidence of nonrelapse mortality (NRM) was comparable in recipients of HID (34%) and ISD grafts (38%) (P = .85). The 3-year probability of overall survival (OS) was higher in HID patients (42%) than in ISD (20%) (P = .048) patients. Our comparisons suggest that HID transplants can achieve a stronger graft-versus-leukemia (GVL) effect than ISD for high-risk acute leukemia patients. The outcomes of an historic comparison of 117 consecutive, high-risk, acute leukemia patients undergoing hematopoietic stem cell transplantation (HSCT) from HLA-mismatched/haploidentical donors (HID, n = 81) or HLA-identical sibling donors (ISD, n = 36) without the use of in vitro T cell depletion (TCD), between the period of January 2005 and April 2009 were compared. Full engraftment was achieved in 98% of patients in the HID group and 97% in the ISD group. The cumulative incidences of grades II–IV acute graft-versus-host disease (aGVHD) in the HID and ISD cohorts were 49% and 24%, respectively (P = .014) with a relative risk (RR) of 2.99 (1.25-7.21) (P = .014). The incidence of chronic GVHD (cGVHD) did not differ significantly between the 2 cohorts. The 2-year cumulative incidence of relapse was significantly lower in HID (26%) than in ISD patients (49%) (P = .008). The 2-year cumulative incidence of nonrelapse mortality (NRM) was comparable in recipients of HID (34%) and ISD grafts (38%) (P = .85). The 3-year probability of overall survival (OS) was higher in HID patients (42%) than in ISD (20%) (P = .048) patients. Our comparisons suggest that HID transplants can achieve a stronger graft-versus-leukemia (GVL) effect than ISD for high-risk acute leukemia patients. IntroductionHematopoietic stem cell transplantation (HSCT) is 1 of the best, and sometimes the only, option for the treatment of leukemia, particularly for patients with high-risk leukemia. It is widely known that the relapse rate of allogeneic HSCT (allo-HSCT) is lower than that of auto- or syngeneic HSCT. Immune cells derived from the donor contribute to the eradication of leukemia after allo-HSCT, whereas auto- or syngeneic HSCT have no graft-versus-leukemia (GVL) effect. The GVL effect is usually identified in retrospective analyses of relapse rates following HSCT from human leukocyte antigen (HLA)-identical sibling donors for leukemia 1Ringden O. Zwaan F. Hermans J. Gratwohl A. European experience of bone marrow transplantation for leukemia.Transplant Proc. 1987; 19: 2600-2604PubMed Google Scholar and has subsequently been extensively confirmed in other transplant settings. Kanda et al. 2Kanda Y. Chiba S. Hirai H. et al.Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000).Blood. 2003; 102: 1541-1547Crossref PubMed Scopus (130) Google Scholar reported that the incidence of relapse was dramatically decreased with 1-locus–mismatched family member HSCT compared to matched HSCT for high-risk diseases (19% versus 47%; P = .004). Reports from IBMTR also showed that in acute leukemia, relapse risk was lower after alternative-donor compared with HLA-identical sibling transplants. This difference was statistically significant (P < .05) for 2-HLA-antigen–mismatched related and HLA-antigen–mismatched unrelated donors 3Szydlo R. Goldman J.M. Klein J.P. et al.Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.J Clin Oncol. 1997; 15: 1767-1777Crossref PubMed Scopus (398) Google Scholar.Great progress has been made in haploidentical donor (HID) HSCT over the past 20 years, and it has become a feasible option for leukemia patients especially with high-risk features without a HLA-identical sibling donor (ISD). It has been speculated that HID HSCT may potentially exert a strong GVL effect. However, comparative clinical studies to confirm the potential beneficial GVL effects are lacking. One possible reason for the lack of such studies is that most HID HSCT is performed with an in vitro T cell depletion (TCD) et transplantation from related donors other than HLA-identical PubMed Scopus Google et of related donors to allogeneic marrow 1997; Google J. 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Chiba S. Hirai H. et al.Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000).Blood. 2003; 102: 1541-1547Crossref PubMed Scopus (130) Google et transplantation from unrelated donors for treatment of effect of for 1 Google O. et graft-versus-leukemia effect using matched unrelated donors is not to HLA-identical siblings for hematopoietic stem cell PubMed Scopus Google Klein J. et survival with transplantation of matched unrelated versus unrelated or human leukocyte haploidentical family donor marrow grafts for the treatment of a treatment for recipients of donor PubMed Scopus Google Kanda et al. [2Kanda Y. Chiba S. Hirai H. et al.Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000).Blood. 2003; 102: 1541-1547Crossref PubMed Scopus (130) Google Scholar reported that the cumulative incidence of relapse was after matched HSCT for was not significantly from that after 1-locus–mismatched HSCT P = the incidence was versus (P = for high-risk et al. et transplantation from unrelated donors for treatment of effect of for 1 Google Scholar] reported that was a for the probability of relapse to in the matched unrelated group than in the matched unrelated group donor HSCT has comparable or lower relapse rate than ISD HSCT 3Szydlo R. Goldman J.M. Klein J.P. et al.Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.J Clin Oncol. 1997; 15: 1767-1777Crossref PubMed Scopus (398) Google O. et graft-versus-leukemia effect using matched unrelated donors is not to HLA-identical siblings for hematopoietic stem cell PubMed Scopus Google from the showed that 3-year probability of relapse was after unrelated HSCT for was not significantly from that after ISD HSCT P = the incidence was versus (P = for diseases [3Szydlo R. Goldman J.M. 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However, the to engraftment rate and were comparable between the 2 cohorts. was a a higher risk of recipients of haploidentical transplants compared to ISD transplants P = whereas was lower recipients of haploidentical transplants. This may from the difference between the 2 was a significant in not a comparative reported et al. et and marrow transplantation can achieve comparable outcomes with HLA-identical sibling PubMed Scopus Google for patients was comparable for ISD and HID with a 2-year of and in the was higher than in that of the high-risk disease in the The of high-risk patients in that was and for ISD and HID cohorts. that disease can dramatically 3Szydlo R. Goldman J.M. Klein J.P. et al.Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.J Clin Oncol. 1997; 15: 1767-1777Crossref PubMed Scopus (398) Google et hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of PubMed Scopus Google et of acute with HLA-mismatched/haploidentical and bone marrow 15: Full Full PubMed Scopus Google The for acute GVHD treatment PubMed Scopus Google from the IBMTR showed that the 3-year was and for and diseases after ISD HSCT [3Szydlo R. Goldman J.M. Klein J.P. et al.Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.J Clin Oncol. 1997; 15: 1767-1777Crossref PubMed Scopus (398) Google et al. The for acute GVHD treatment PubMed Scopus Google Scholar reported that 1 of the with significantly 2-year was a high-risk the of P < the 2-year for haploidentical patients was and respectively to the in the group and in the high-risk group et hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of PubMed Scopus Google 2009 the 2-year for haploidentical acute leukemia patients in and high-risk was and for and and for respectively et of acute with HLA-mismatched/haploidentical and bone marrow 15: Full Full PubMed Scopus Google The of patients between the January 2005 to April and the et al. January to were not the difference in the between the 2 studies the transplant from comparative group between January and showed that the was to the et al. and after HID and unrelated et matched related donor transplantation can achieve outcomes comparable to unrelated donor transplantation for patients with 15: PubMed Scopus Google of the of patients between the et al. and that comparative reported in 2009 were not and the of high-risk patients was to have in the than in the et al. The for the is in the that may a for the higher probability of survival was achieved for HID patients in the the comparative reported et al. et and marrow transplantation can achieve comparable outcomes with HLA-identical sibling PubMed Scopus Google survival for patients with disease was comparable for ISD and HID with 2-year of survival of and It that the in ISD patients in the was to that in the However, it that a ISD and HID a of risk from or also with and chronic a of patients a of and and for survival may have to the of transplantation in high-risk patients has survival in other studies 2Kanda Y. Chiba S. Hirai H. et al.Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000).Blood. 2003; 102: 1541-1547Crossref PubMed Scopus (130) Google R. Goldman J.M. Klein J.P. et al.Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.J Clin Oncol. 1997; 15: 1767-1777Crossref PubMed Scopus (398) Google O. et graft-versus-leukemia effect using matched unrelated donors is not to HLA-identical siblings for hematopoietic stem cell PubMed Scopus Google A. et donor recipients have outcomes to matched sibling a matched PubMed Scopus Google R. et of graft-versus-host and survival after marrow transplantation for patients with leukemia or PubMed Scopus Google the significantly lower relapse rate and higher survival probability for HID patients than for ISD HID HSCT with vitro T cell depletion of ISD donors in patients with high-risk leukemia the showed that a lower relapse a engraftment and a higher survival probability was achieved with HID patients than with ISD patients. The suggest that HID HSCT achieve a effect for high-risk acute leukemia patients. IntroductionHematopoietic stem cell transplantation (HSCT) is 1 of the best, and sometimes the only, option for the treatment of leukemia, particularly for patients with high-risk leukemia. It is widely known that the relapse rate of allogeneic HSCT (allo-HSCT) is lower than that of auto- or syngeneic HSCT. Immune cells derived from the donor contribute to the eradication of leukemia after allo-HSCT, whereas auto- or syngeneic HSCT have no graft-versus-leukemia (GVL) effect. The GVL effect is usually identified in retrospective analyses of relapse rates following HSCT from human leukocyte antigen (HLA)-identical sibling donors for leukemia [1Ringden O. Zwaan F. Hermans J. Gratwohl A. European experience of bone marrow transplantation for leukemia.Transplant Proc. 1987; 19: 2600-2604PubMed Google Scholar and has subsequently been extensively confirmed in other transplant settings. Kanda et al. 2Kanda Y. Chiba S. Hirai H. et al.Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000).Blood. 2003; 102: 1541-1547Crossref PubMed Scopus (130) Google Scholar reported that the incidence of relapse was dramatically decreased with 1-locus–mismatched family member HSCT compared to matched HSCT for high-risk diseases (19% versus 47%; P = .004). Reports from IBMTR also showed that in acute leukemia, relapse risk was lower after alternative-donor compared with HLA-identical sibling transplants. This difference was statistically significant (P < .05) for 2-HLA-antigen–mismatched related and HLA-antigen–mismatched unrelated donors 3Szydlo R. Goldman J.M. Klein J.P. et al.Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.J Clin Oncol. 1997; 15: 1767-1777Crossref PubMed Scopus (398) Google Scholar.Great progress has been made in haploidentical donor (HID) HSCT over the past 20 years, and it has become a feasible option for leukemia patients especially with high-risk features without a HLA-identical sibling donor (ISD). It has been speculated that HID HSCT may potentially exert a strong GVL effect. However, comparative clinical studies to confirm the potential beneficial GVL effects are lacking. One possible reason for the lack of such studies is that most HID HSCT is performed with an in vitro T cell depletion (TCD) et transplantation from related donors other than HLA-identical PubMed Scopus Google et of related donors to allogeneic marrow 1997; Google J. S. et marrow transplantation from family donors for acute experience of PubMed Scopus Google Y. et for with marrow cells and Google F. A. A. et engraftment of T haploidentical transplants in leukemia patients of human cells to bone marrow Google F. A. A. et high-risk acute leukemia with stem cells from related donors with PubMed Scopus Google F. A. A. et hematopoietic a in patients with acute leukemia risk of Clin Oncol. PubMed Scopus Google et of and depletion of bone marrow the and of in the of bone marrow transplant PubMed Scopus Google F. Y. The haploidentical option for high-risk PubMed Scopus Google F. F. et of haploidentical hematopoietic stem cell transplantation in with high-risk acute a risk of outcomes for patients in PubMed Scopus Google The lack of a donor T cell to the overall potential of the compared with T a for HLA-mismatched/haploidentical transplantation without in vitro The in of the and donor T cell and the of the of donor hematopoietic stem cells using the donor treatment with for the of graft-versus-host disease of stem cell transplantation and bone marrow transplantation et hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of PubMed Scopus Google for HID HSCT without in vitro have been achieved et hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of PubMed Scopus Google et of acute with HLA-mismatched/haploidentical and bone marrow 15: Full Full PubMed Scopus Google et matched related donor transplantation can achieve outcomes comparable to unrelated donor transplantation for patients with 15: PubMed Scopus Google HID HSCT has a stronger GVL effect is transplant The of retrospective was to transplantation outcomes in a of high-risk acute leukemia patients HSCT from HID or ISD without in vitro
Wang et al. (Mon,) studied this question.
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