scholarly journals First phase insulin release and glucose tolerance in children with Fanconi anemia after hematopoietic cell transplantation

2009 ◽  
Vol 53 (2) ◽  
pp. 191-196 ◽  
Author(s):  
Lynda E. Polgreen ◽  
William Thomas ◽  
Margaret L. MacMillan ◽  
John E. Wagner ◽  
Antoinette Moran ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Cell Transplantation ◽  
Insulin Release ◽  
Fanconi Anemia ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
First Phase Insulin Release

scholarly journals Bone Mineral Density in Children with Fanconi Anemia after Hematopoietic Cell Transplantation

2015 ◽  
Vol 21 (5) ◽  
pp. 894-899 ◽  
Author(s):  
Anna Petryk ◽  
Lynda E. Polgreen ◽  
Jessie L. Barnum ◽  
Lei Zhang ◽  
James S. Hodges ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Cell Transplantation ◽  
Bone Mineral ◽  
Fanconi Anemia ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Mineral Density

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

Blood ◽  
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.

Kidney complications in 107 Fanconi anemia patients submitted to hematopoietic cell transplantation

2021 ◽  
Author(s):  
Mariana Munhoz da Cunha ◽  
Fellype Carvalho Barreto ◽  
Samantha Nichele ◽  
Joanna Trennepohl ◽  
Lisandro Ribeiro ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Fanconi Anemia ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell

Alternative Donor Hematopoietic Cell Transplantation for Patients with Fanconi Anemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3081-3081
Author(s):  
Margaret L. MacMillan ◽  
Bruce R. Blazar ◽  
Todd E. Defor ◽  
Kathryn E. Dusenbery ◽  
Arne Slungaard ◽  
...  
Keyword(s):  
Relative Risk ◽  
Cell Transplantation ◽  
Fanconi Anemia ◽  
Graft Failure ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Probability Of Survival ◽  
Alternative Donor

Abstract Abstract 3081 Hematopoietic cell transplantation (HCT) is the only proven curative therapy for the hematological abnormalities in patients with Fanconi anemia (FA). In the mid-1990s, survival after alternative donor (AD)-HCT was reported to be 18% with excessive rates of regimen-related toxicity, graft failure, graft-versus-host-disease (GVHD) and opportunistic infections (OI). Between 1990 and 2010, 127 FA patients underwent AD-HCT at the University of Minnesota using one of 5 consecutive, prospective phase I-II total body irradiation (TBI) containing clinical trials, representing the largest single center experience. All patients received cyclophosphamide (CY, 40 mg/kg) and single fraction TBI. Sequential changes were made to prevent GVHD, graft failure and OI and ultimately enhance survival; in 1994, all patients received T cell depleted (TCD) bone marrow (BM) or umbilical cord blood (UCB) to reduce GVHD; in 1999, fludarabine (FLU) was added to enhance engraftment; in 2003, thymic shielding (TS) was added to reduce OI risk; and in 2006, TBI dose reduction was evaluated to reduce toxicity. Over this time period, HLA-matched unrelated donor BM was the donor of choice with partially HLA matched BM and UCB only used as alternatives. Neutrophil recovery was twice as likely after FLU-containing regimens than non-FLU containing regimens and was not deleteriously affected by TS or reducing TBI dose to 300cGy. Grade II-IV acute GVHD was significantly reduced by the use of TCD (18%) compared to T replete BM or UCB (50% and 38%, respectively: p<0.01). Similarly, chronic GVHD was significantly lower with TCD BM (9%) vs T replete BM or UCB (25% and 15%, respectively; p=0.04). For the entire cohort of 127 patients, the probability of survival was 61% at 1 year and 54% at 5 years with a median follow-up of 9 years. Mortality was higher in recipients who were older (>10 years) or CMV seropositive, received any transfusions before HCT, or developed OI before HCT (Table). Mortality was lowest using CY/FLU/ATG, TBI 300 cGy with TS (Trial 5, relative risk [RR] 0.1; p<0.01). For 10 patients on Trial 5 who had no prior history of transfusions or OI, incidences of neutrophil and platelet are 100% and 100%, acute and chronic GVHD 17% and 0%, and probability of survival is 92%. Table: Factors associated with 3 year mortality: Multivariate analysis Factors Relative Risk of Mortality (95% CI) P-value Trial*     2: CY/ATG/TBI 450-600, CSA/MP 1.0     3: CY/FLU/ATG/TBI 450, CSA/MP 0.3 (0.1–.7) <0.01     4: CY/FLU/ATG/TBI 450+TS, CSA/MP 0.2 (0.1–0.7) 0.01     5: CY/FLU/ATG/TBI 300+TS, CSA/MP or MMF 0.1 (0.04–0.3) <0.01 Donor Type     Matched URD Marrow 1.0     Mismatched URD Marrow 0.3 (0.1–0.8) <0.01     Mismatched RD Marrow 0.3 (0.1–2.3) 0.22     Single or Double UCB 2.0 (0.9–4.6) 0.08 Age at Transplant     <10 years 1.0     10–17 years 2.4 (1.2–5.0) 0.01     18+ years 3.1 (1.4–7.0) <0.01 Prior OI     None 1.0     Yes 3.2 (1.5–6.9) <0.01 Prior Transfusions     None     Yes 2.4 (1.0–5.8) 0.05 CMV Serostatus     Patient negative/donor negative 1.0     Patient negative/donor positive 1.5 (0.7–3.4) 0.34     Patient positive 2.2 (1.1–4.3) 0.03 * Trial 1 (CY/TBI 450, MTX/MP or CSA) was excluded as there were only 8 patients in this group and a number of demographic and disease factors were unknown. Substantial progress has been made in the successful application of AD-HCT for FA. These data support the urgency of transplant prior to the onset of severe pancytopenia when risk of OI and transfusions are more likely, particularly when a suitable BM donor is available. While other regimens are being explored, CY/FLU/ATG/TBI300 with TS should be considered a new standard of care for FA patients undergoing AD-HCT. Disclosures: No relevant conflicts of interest to declare.

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