Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromes

Martino, Rodrigo; Caballero, Marı́a Dolores; Simón, Jose Antonio Pérez; Canals, Carmen; Solano, Carlos; Urbano-Ispizúa, Álvaro; Bargay, Joan; León, Ángel; Sarrà, Josep; Sanz, Guillermo; Moraleda, José Marı́a; Brunet, Salut; Miguel, Jesús F. San; Sierra, Jorge

doi:10.1182/blood-2002-02-0400

Cited by 166 publications

(87 citation statements)

References 18 publications

(13 reference statements)

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“…Unrelated umbilical cord blood (UCB) HSCT had similarly successful outcomes as volunteer unrelated donors (URD) transplants using RI conditioning [18]. These data add to an increasing body of evidence [19][20][21][22] that RI HSCT can be clinically potent with an antileukemia effect capable of inducing and maintaining a long term remission in these aggressive myeloid malignancies. The preferred intensity within the spectrum of RI or non-MA conditioning regimens for myeloid leukemia continues to be a subject of study [16,23].…”

Section: Discussionmentioning

confidence: 83%

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

et al. 2007

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We evaluated the efficacy of hematopoietic stem cell transplantation (HSCT) using reduced intensity (RI) vs. myeloablative (MA) conditioning for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome. Thirty two patients (median age 54) who underwent a RI HSCT (2000HSCT ( -2003 were compared with 187 patients (median age 39) who received a MA transplant (1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003). Neutrophil engraftment was more rapid in the RI group (median 11.5 vs. 21 days). Platelet recovery was similar and graft failure was infrequent. The incidence of graft-versus-host disease (GVHD) and treatment-related mortality was similar though relapse was more frequent after RI conditioning (RR 2.2 [95% CI 5 1.1-4.6] P 5 0.03). At 2 years, disease-free survival (DFS) (31% vs. 30%, P > 0.1) and overall survival (33% vs. 35%, P > 0.1) were comparable between RI and MA groups, respectively. We suggest that RI allografts can yield satisfactory DFS both for older as well as younger patients with pre-existing comorbidities, who are ineligible for MA allografts. Advances in GVHD management and new approaches for relapsed or refractory disease are necessary to improve these outcomes. Am. J. Hematol. 82:867-872, 2007. V

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Section: Discussionmentioning

confidence: 83%

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

et al. 2007

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“…7,9,17 We and others have observed a strong association between GVHD and decreased risk of disease progression in both myeloid and lymphoid malignancies. 9,[18][19][20][21] The occurrence of moderate to severe GVHD, however, also increases the risk of developing life-threatening infections. [21][22][23][24] Elderly or debilitated patients tolerate GVHD and its treatment poorly, thus explaining our risk factors for TRM and OS.…”

Section: Discussionmentioning

confidence: 99%

Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial

Gómez-Núñez

Martino

Caballero

et al. 2004

Bone Marrow Transplant

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Summary:Over a 3-year period, 145 patients ineligible for myeloablative conditioning underwent reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (SCT) from an HLA-identical sibling in a prospective study. The median age was 54 years, 88 patients were male and 61 patients were beyond the early-intermediate phase of their disease. The 100-day probability of developing grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year probability of developing chronic extensive GVHD was 41%. The 1-year probabilities of transplant-related mortality (TRM), overall (OS) and progression-free survival were 20, 60 and 52%, respectively. Multivariate analyses found a better OS in: (i) patients o60 years; and (ii) recipients of a first SCT; and a higher TRM in: (i) age 460 years, (ii) recipients of a prior autologous SCT, and (iii) an ECOG performance status 41. The 1-year TRM in patients with 0 or 1 and 42 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively (Po0.001). In summary, our study shows that elderly patients have a higher TRM following an RIC protocol. However, age by itself should not preclude these RIC transplants, since TRM appears to be unacceptably high only in the presence of additional adverse factors. Allogeneic stem cell transplantation (alloSCT) is a wellestablished treatment approach for numerous hematological malignancies. However, high-dose conditioning regimens designed to both control the malignancy and to prevent graft rejection are associated with a high mortality and a high incidence of acute and long-term side effects, especially in elderly or debilitated patients. A potential way to overcome this problem is by decreasing the intensity of chemotherapy and/or radiotherapy given prior to transplantation. Several groups of investigators have developed reduced-intensity conditioning (RIC) regimens that lead to successful engraftment in patients with hematological and nonhematological malignancies, without the extrahematologic toxicities of traditional myeloablative transplants. [1][2][3][4][5][6] Based on numerous phase II trials, RIC are able to induce graft-versus-leukemia/tumor (GVL) effects with acceptable levels of extrahematologic toxicity. Thus, these attenuated regimens have been used mostly in older patients or patients with pre-existing organ dysfunction who would otherwise have a high risk of transplant-related mortality (TRM) after a myeloablative alloSCT. To date however, risk factors for TRM and their impact on overall survival (OS) after RIC transplants have not been described. We report here results of a prospective multicenter study of two RIC regimens (for myeloid and lymphoid malignancies) followed by allogeneic peripheral blood SCT (PBSCT) that is being conducted in several institutions in Spain, with special emphasis on pretransplant variables that influenced early TRM and OS. Patients and methods Patient selectionEligibility criteria for entry into this RIC allogeneic PBSCT program included patients with a myeloid o...

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“…15 In this setting of patients, prognosis is still poor and this group may benefit from new drug developments and alternative approaches for disease control and delay of a novel relapse. 16,17 In patients with relapsed AML, depending on cytogenetic profile, age and time of first remission, cytarabine-based salvage chemotherapy is sometimes satisfactory. 15,18,19 However, only a few randomized studies address this issue, which thus remains a gray area.…”

Section: Discussionmentioning

confidence: 99%

“…3 Cytogenetic abnormalities are among the most widely recognized risk factors in AML patients. 4 AML with karyotype t(8;21), inv (16), t(16;16), and t(15;17) are expected to be controlled with chemotherapy alone, and patients with these forms of AML are thus categorized into a favorable cytogenetic risk group. 4,5 Therefore, indication of ASCT for patients in this group is considered not at the first complete remission but at the state of relapse, after the second remission or just in case of failure to achieve remission.…”

Section: Introductionmentioning

confidence: 99%

Outcomes of allogeneic stem cell transplantation among patients with acute myeloid leukemia presenting active disease: Experience of a single European Comprehensive Cancer Center

De-Mello

Pinho-Vaz

Branca

et al. 2016

Rev. Assoc. Med. Bras.

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OutcOmes Of allOgeneic stem cell transplantatiOn amOng patients with acute myelOid leukemia presenting active disease: experience Of a single eurOpean cOmprehensive cancer center rev assoC med bras 2016; 62 (7) Introduction: Allogeneic hematopoietic stem cell transplantation (ASCT) represents a potentially curative approach for patients with relapsed or refractory acute myeloid leukemia (AML). We report the outcome of relapsed/refractory AML patients treated with ASCT. Method: A retrospective cohort from 1994 to 2013 that included 61 patients with diagnosis of relapsed/refractory AML. Outcomes of interest were transplant--related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), relapse incidence, progression-free survival (PFS) and overall survival (OS). Statistical significance was set at p<0.05. Results:The median age was 61 years (range 1 to 65). The cumulative incidence of 90 days, 1 year, and 3 years TRM were 60%, 26.7%, and 13.3%, respectively (p<0.001). The incidence of relapse was 21.7% at 1 year, 13% at 3 years, and 8.7% at 5 years. Median OS was estimated to be 8 months ) and median PFS, 3 months (95CI 1.835-4.165). Conclusion:In our cohort, TRM in first years after ASCT remains considerable, but ASCT in this setting seems to be a good choice for AML patients with active disease. However, novel approaches are needed to reduce TRM and relapse in this set of patients.

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Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndromes

Cited by 166 publications

References 18 publications

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

Elderly age and prior autologous transplantation have a deleterious effect on survival following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning: results from the Spanish multicenter prospective trial

Outcomes of allogeneic stem cell transplantation among patients with acute myeloid leukemia presenting active disease: Experience of a single European Comprehensive Cancer Center

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