Allogeneic Hematopoietic Cell Transplantation for Fanconi Anemia in Patients With Pretransplantation Cytogenetic Abnormalities, Myelodysplastic Syndrome, or Acute Leukemia

Purpose Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed. Patients and Methods We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007. Results Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (≤ v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (≤ v > 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival. Conclusion Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival.

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Long-Term Survival and Late Effects Among 1-Year Survivors of Second Allogeneic Hematopoietic Cell Transplantation (2nd Allo HCT) for Relapsed Acute Leukemia and Myelodysplastic Syndrome: A Report from the Cibmtr

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2013.12.073 ◽

2014 ◽

Vol 20 (2) ◽

pp. S64

Author(s):

Christine Duncan ◽

Navneet S. Majhail ◽

Ruta Brazauskas ◽

Zhiwei Wang ◽

Jean-Yves Cahn ◽

...

Keyword(s):

Acute Leukemia ◽

Myelodysplastic Syndrome ◽

Cell Transplantation ◽

Late Effects ◽

Hematopoietic Cell Transplantation ◽

Hematopoietic Cell ◽

Allogeneic Hematopoietic Cell Transplantation ◽

Term Survival ◽

Long Term Survival

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Results of Allogeneic Hematopoietic Cell Transplantation in Persons with Fanconi Anemia and Pretransplant Cytogenetic Abnormalities, Myelodysplastic Syndrome, or Acute Leukemia

Blood ◽

10.1182/blood.v118.21.838.838 ◽

2011 ◽

Vol 118 (21) ◽

pp. 838-838

Author(s):

Mouhab Ayas ◽

Jennifer Le-Rademacher ◽

H. Joachim Deeg ◽

Robert Peter Gale ◽

Stella M. Davies ◽

...

Keyword(s):

Bone Marrow ◽

Acute Leukemia ◽

Myelodysplastic Syndrome ◽

Cell Transplantation ◽

Fanconi Anemia ◽

Cumulative Incidence ◽

Graft Failure ◽

Hematopoietic Cell Transplantation ◽

Hematopoietic Cell ◽

Conditioning Regimens

Abstract Abstract 838 Background: Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in persons with Fanconi anemia (FA). However, results in those with pretransplant cytogenetic abnormalities (CA), myelodysplastic syndrome (MDS) or acute leukemia (AL) are less favorable, although only limited data are available. Thus, the current study was designed to use data from the Center for International Blood and Marrow Transplant Research (CIBMTR) to evaluate the outcomes of these patients after HCT. Patients and Methods: This is a retrospective analysis of 113 FA patients with CA (n=54), MDS (n=45), or AL (n=14) before allogeneic HCT, and who were reported to CIBMTR from 1985 to 2007 by 46 centers worldwide. Overall survival (OS) probability was estimated using the Kaplan-Meier method. Engraftment and acute and chronic graft-vs-host-disease (GvHD) were determined using cumulative incidence estimates to accommodate competing risks. Univariate analyses were conducted to evaluate the prognostic impact of key variables. The small sample size precluded multivariate analysis. Fifty four patients had CA including complex abnormalities (n=18), chromosome (Chr) 1 abnormalities (n=8), chr 3 abnormalities (n=1), chr 5 abnormalities (n=3), chr 7 abnormalities (n=4) and other non-complex abnormalities (n=20). Pretransplant conditioning regimens were radiation-based in 67 patients and chemotherapy-based in 46 patients. The donor source was bone marrow/peripheral blood (matched related, n=82; unrelated, n=16), or cord blood (related, n=2; unrelated, n=13). Results: Absolute neutrophil count (ANC) recovery occurred in 78% and 85% of patients, at day 28 and day 100, respectively. At day 100, the cumulative incidences of acute GvHD grade II–IV and III–IV were 26% (95% confidence intervals [CI] 19–35), and 12% (95% CI 7–19), respectively. Chronic GvHD cumulative incidences were 20%, 23%, and 23% at 1, 3, and 5 years, respectively. Primary graft-failure occurred in 18 patients. Cumulative incidence of secondary graft-failure at 2 years was 9% (95% CI 4–15). Survival probabilities were 64%, 58%, and 55% at 1, 3, and 5 years, respectively. Exclusion of subjects with chr 1 abnormalities did not alter the results (log-rank P value=.81). In univariate analysis, among the entire cohort, none of the following variables affected survival: use of fludarabine or radiation in the conditioning regimen, the presence of AL/MDS as compared to only CA, or year of transplant. Age at transplant was the only variable significantly correlated with 5-year OS (≤ 14 years vs. > 14 years, 69% vs. 39%, respectively; P =0.001). When analysis was restricted to recipients of related donor HCT (n=82), age again correlated with 5-year survival (≤ 14 years vs. > 14 years, 78% vs. 34%, respectively; P <.001); additionally, patients with CA pretransplant had better survival than those with MDS or AL (5-year OS: 67% vs. 43%, P =0.03). Conclusion: Our analysis indicates that persons with FA and pretransplant CA, MDS, or AL have a reasonable survival with HCT. The analysis also suggests that survival may be better in younger persons and in those with only CA pretransplant. No firm conclusions can be drawn from this study regarding the impact of the conditioning regimens; the current data, however, suggest that radiation-based conditioning regimens are not associated with a survival advantage as has been suggested by previously published data. Disclosures: No relevant conflicts of interest to declare.

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