Matched and Mismatched Allogeneic Stem-Cell Transplantation From Unrelated Donors Using Combined Graft-Versus-Host Disease Prophylaxis Including Rabbit Anti–T Lymphocyte Globulin

Finke, Jürgen; Schmoor, Claudia; Lang, Helmut; Potthoff, Karin; Bertz, Hartmut

doi:10.1200/jco.2003.03.129

Cited by 69 publications

(61 citation statements)

References 25 publications

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“…This reflects the 5-year RFS and OS rates of 42 and 51%, respectively, for all patients. These results are consistent or even superior to those of published reports using myeloablative regimens, 15,[18][19][20] and are particularly encouraging considering that 51% of patients were not in CR at HCT, 24% patients had over 20% blasts in the BM and 27% presented blasts in the peripheral blood. Previous studies reported OS rates of 20-30% in refractory AML using standard conditioning regimens for HCT.…”

Section: Discussionsupporting

confidence: 73%

“…12 The relatively low rate of severe acute GVHD and persistent chronic GVHD in unrelated patients might be attributable to the successful use of ATG-F, as reported by our group. 15 In particular, the successful use of ATG-F might be reflected in the lower (although not statistically significant) rate of chronic extensive GVHD after unrelated HCT compared with related HCT. It is noteworthy that, on taking into account the lower relapse risk after unrelated HCT compared with related HCT, a clinically significant negative influence on the GVL effect by ATG-F could not be observed.…”

Section: Discussionmentioning

confidence: 99%

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Improved outcome in relapsed and refractory myeloid malignancies for unrelated vs related donor allogeneic peripheral blood-derived hematopoietic cell transplantation

Denz

Bertz

Ihorst

et al. 2010

Bone Marrow Transplant

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There are limited data on the comparison of unrelated vs related peripheral blood-derived hematopoietic cell transplantation (HCT) in patients with AML and its implications in high-risk patients. In this single-center retrospective study, we report on a total of 92 consecutive patients with AML (n ¼ 87) or myelodysplastic syndrome (MDS; n ¼ 5), who were treated between 1996 and 2006 with a uniform preparative regimen of BU and CY and peripheral bloodderived HCT from related (n ¼ 46) or unrelated donors (n ¼ 46). At transplantation, 45 patients were in CR, 11 were untreated and 36 had relapsed or refractory disease. Median follow-up was 864 days after transplant (range 24-3798). At 5 years after HCT, cumulative incidences for relapse (32% of all patients) and nonrelapse mortality (NRM; 17%) were low. The 5-year relapse-free survival (RFS) and OS rates were 36 and 45% for related and 47 and 57% for unrelated patients, respectively (RFS P ¼ 0.43; OS P ¼ 0.28). High-risk patients with an unfavorable remission status before HCT benefited more from unrelated HCT than related HCT, showing a significantly better 5-year RFS of 46% (95% confidence interval (CI) 27-65) vs 22% (95% CI 4-40) (P ¼ 0.04). Unrelated HCT benefited high-risk AML patients with an unfavorable remission status better than related HCT.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Improved outcome in relapsed and refractory myeloid malignancies for unrelated vs related donor allogeneic peripheral blood-derived hematopoietic cell transplantation

Denz

Bertz

Ihorst

et al. 2010

Bone Marrow Transplant

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“…5 While the efficacy of ATG to prevent GVHD and to reduce nonrelapse mortality after myeloablative HSCT has been demonstrated in several studies, the role of ATG in reduced-intensity conditioning has not been evaluated. [6][7][8][9][10] However, reduced-intensity conditioning with BU and FLU was safe even without ATG in 24 patients as shown by our group. 11 In order to assess the impact of ATG, we retrospectively compared the engraftment, incidence and severity of GVHD and survival after BU-and FLU-based reduced-intensity conditioning with or without ATG in patients who had received peripheral blood stem cell transplantation (PBSCT) from HLAidentical siblings.…”

Section: Discussionmentioning

confidence: 95%

Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation – a retrospective analysis

Schetelig

Bornhäuser

Kiehl

et al. 2003

Bone Marrow Transplant

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Summary:It is unknown whether the addition of antithymocyte globulin (ATG) to reduced-intensity conditioning with busulfan (BU) and fludarabine (FLU) is beneficial in HLA-identical sibling transplantation. Therefore, we analyzed retrospectively data on 83 patients, who received peripheral blood stem cells from HLA-identical siblings after conditioning with either 8 mg/kg BU and 150 mg/m 2 FLU (n ¼ 45) or 8 mg/kg BU, 180 mg/m 2 FLU and 40 mg/ kg ATG (n ¼ 38). Graft-versus-host disease (GVHD) prophylaxis consisted of CSA alone (n ¼ 32) or a combination with either MTX or MMF (n ¼ 51). The median age was 52 years. Graft failure occurred in two patients after BU/FLU and in three after BU/FLU/ATG (P ¼ 0.66). After conditioning with BU/FLU, platelet recovery was significantly faster (P ¼ 0.017), and less platelet (Po0.001) and red blood cell (P ¼ 0.002) support was needed. Incidences of acute GVHD grades II and IV were 46 and 49%, respectively. Limited chronic GVHD occurred more often after BU/FLU compared to BU/FLU/ ATG (54 vs 23%, P ¼ 0.02). The overall survival, nonrelapse and relapse mortality did not differ significantly. We conclude that in peripheral blood stem cell transplantation from HLA-identical siblings after reduced-intensity conditioning with BU and FLU, ATG has no major impact on the rate of graft rejection and acute GVHD, but it reduces the incidence of limited chronic GVHD. Reduced-intensity conditioning regimens with busulfan (BU), fludarabine (FLU) and antithymocyte globulin (ATG) are increasingly used in related and unrelated hematopoietic stem cell transplantation (HSCT). 1 While the use of ATG as an additional drug for graftversus-host disease (GVHD) prophylaxis is widely accepted in unrelated transplantation, the application in HLA-identical sibling transplantation is a matter of debate. ATG-Fresenius is a polyclonal IgG antibody raised in rabbits against the Jurkat T cell line. 2 The antibody had been incorporated into dose-reduced conditioning regimens for two reasons: first, ATG given before transplantation exerts T-cell depletion of the recipient, which facilitates donor stem cell engraftment after nonmyeloablative doses of BU and FLU and second, antibody persisting in the recipient beyond transplantation exerts in vivo depletion of donor T cells, thereby possibly reducing the risk for acute and chronic GVHD. 3,4 However, ATG has considerable short-term toxicity. 5 While the efficacy of ATG to prevent GVHD and to reduce nonrelapse mortality after myeloablative HSCT has been demonstrated in several studies, the role of ATG in reduced-intensity conditioning has not been evaluated. [6][7][8][9][10] However, reduced-intensity conditioning with BU and FLU was safe even without ATG in 24 patients as shown by our group. 11 In order to assess the impact of ATG, we retrospectively compared the engraftment, incidence and severity of GVHD and survival after BU-and FLU-based reduced-intensity conditioning with or without ATG in patients who had received peripheral blood stem cell transplantation (PBSCT...

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“…8 However, the use of reinforced GVHD prophylaxis with ex vivo T-cell depletion can mitigate the impact of mismatching. 9,10 From this perspective, haplo donors present different advantages: short time to find a donor, possibility of donor-lymphocyte infusion, and/or donors are not limited in ethnic minority patients. In addition, haplo-HSCT can be a valid option for patients with a relatively large body weight, for whom an optimal cell dose from UCB is rarely found.…”

Section: Introductionmentioning

confidence: 99%

Unrelated cord blood compared with haploidentical grafts in patients with hematological malignancies

El-Cheikh

Crocchiolo

Fürst

et al. 2015

Cancer

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BACKGROUND:Alternative donors, such as unrelated umbilical cord blood (UCB) and related haploidentical (haplo) donors, are more and more frequently searched for and used for patients who are candidates for allogeneic hematopoietic stem cell transplantation but are without a suitable related or unrelated donor. The aim of the current retrospective study was to compare the outcome of patients after haplo and UCB grafts prepared using a nonmyeloablative conditioning regimen. METHODS: A total of 150 adult patients with high-risk hematologic diseases who underwent allogeneic hematopoietic stem cell transplantation from alternative donors at 2 centers (Paoli-Calmettes Institute [Marseille, France] and Humanitas Cancer Center [Milan, Italy]) were analyzed. Sixty-nine patients had haplo donors and 81 patients had UCB donors. RESULTS: The cumulative incidence of nonrecurrence mortality at 1 year was 23% in the UCB group versus 17% in the haplo group (P 5.39). The incidence of grade 2 to 4 acute graft-versus-host disease and extensive chronic graft-versus-host disease in the UCB group versus the haplo group was 52% versus 29% (P 5.05) and 12% versus 6% (P<.0001), respectively. The overall survival rate at 2 years was 45% in the UCB group (95% confidence interval [95% CI], 34%-56%) versus 69% in the haplo group (95% CI, 58%-80%) (P 5.10). The progression-free survival rate at 2 years was 36% in the UCB group (95% CI, 25%-47%) versus 65% in the haplo group (95% CI, 53%-77%) (P 5.01). CONCLUSIONS: The results of the current study suggest that for patients with high-risk hematological diseases without a related or unrelated donor, haploidentical transplants are a promising alternative option that deserves further investigation. Cancer 2015;121:1809-16. V C 2015 American Cancer Society.KEYWORDS: haploidentical donor, unrelated umbilical cord blood, allogeneic hematopoietic stem cell transplantation, nonmyeloablative conditioning regimen, high-risk hematological diseases. INTRODUCTIONAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially curative for patients with hematologic malignancies. 1 However, one of the most limiting factors for all patients is the unavailability of a donor. Indeed, a matched related donor is found for only 25% to 30% of patients, and a matched unrelated donor (MUD) is found for 40% to 50% of white patients. For all other patients, alternative donors who can be considered include unrelated cord blood (UCB), mismatched unrelated donor (mMUD), or a partial family matched donor (haploidentical donors; haplo). 2,3 UCB offers the advantages of easy procurement and immediate availability, the absence of risk for the donor, and a potentially reduced risk of graft-versus-host disease (GVHD) despite the absence of total human leukocyte antigen (HLA) compatibility. 4,5 Recently, the results of UCB transplants in adult patients with acute leukemia have been reported. The results with UCB transplants were similar to those obtained with MUD or mMUD for leukemia-free survival, but the nonrecur...

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Matched and Mismatched Allogeneic Stem-Cell Transplantation From Unrelated Donors Using Combined Graft-Versus-Host Disease Prophylaxis Including Rabbit Anti–T Lymphocyte Globulin

Abstract: A certain degree of one antigen mismatching may not compromise the outcome after UD SCT when using this rabbit ATG in addition to standard GVHD prophylaxis regimen.

Cited by 69 publications

References 25 publications

Improved outcome in relapsed and refractory myeloid malignancies for unrelated vs related donor allogeneic peripheral blood-derived hematopoietic cell transplantation

Improved outcome in relapsed and refractory myeloid malignancies for unrelated vs related donor allogeneic peripheral blood-derived hematopoietic cell transplantation

Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation – a retrospective analysis

Unrelated cord blood compared with haploidentical grafts in patients with hematological malignancies

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