scholarly journals Comparable Outcomes after HLA-Matched Sibling and Alternative Donor Hematopoietic Cell Transplantation for Children with Fanconi Anemia and Severe Aplastic Anemia

2018 ◽  
Vol 24 (4) ◽  
pp. 765-771 ◽  
Author(s):  
Christen L. Ebens ◽  
Todd E. DeFor ◽  
Rebecca Tryon ◽  
John E. Wagner ◽  
Margaret L. MacMillan
Keyword(s):  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Fanconi Anemia ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Severe Aplastic Anemia ◽  
Alternative Donor ◽  
Matched Sibling

Obesity Adversely Affects Survival of Pediatric Patients with Severe Aplastic Anemia After Hematopoietic Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 652-652
Author(s):  
Collin C. Barker ◽  
Manza- A Agovi ◽  
Brent Logan ◽  
Vikas Gupta ◽  
Hillard M. Lazarus ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Normal Weight ◽  
Hematopoietic Cell ◽  
Severe Aplastic Anemia ◽  
Overweight Children ◽  
Risk Of Death ◽  
The Us ◽  
Matched Sibling

Abstract Abstract 652 Prevalence of obesity in children has been rapidly rising in the last decade in the US and other industrialized countries (US prevalence, ages 2-19, 16%, NHANES, 2008) and it represents a serious health concern. The impact of recipient's weight on mortality after hematopoietic cell transplantation (HCT) for non-malignant diseases is not well characterized. We studied the effect of body mass (BMI) on transplant outcomes in 1,281 patients aged 2-19 years who underwent HCT for severe aplastic anemia from 1990-2005. The study population was divided in five groups based on age-adjusted BMI percentiles. Patients in the <5th, 5-25th, 26-75th, 76-95th and >95th percentile BMI were classified as underweight, at risk for underweight, normal weight, at risk for overweight, and overweight respectively. Cox proportional hazards regression models for survival and acute graft-versus-host disease grade III-IV (aGVHD) were performed using BMI groups as the main effect and the normal weight (26-75th percentile) as the baseline comparison. Two-year overall survival was lower for overweight children (p<0.001, table). The risk of death, adjusted for significant covariates was higher for overweight compared to normal weight children (p=0.001, table). BMI groups were not associated with excess risk for aGVHD. Other significant factors associated with mortality include race and region of US, donor type, performance score at HCT, recipient age, and year of transplant. Risk of death was higher in African American patients (1.84, p=0.009) compared to Caucasians in the US, donors other than HLA-matched sibling and patients who received HCT before 2002. Among recipients of HLA-matched sibling grafts, use of busulfan-containing regimens (3.13, p<0.001) or cyclophosphamide without antithymocyte globulin (ATG) (1.92, p=0.03) had a higher risk of death compared to recipients of cyclophosphamide and ATG. Conditioning regimens in recipients of unrelated donor HCT were not associated with mortality. Among the reported causes of death, organ failure and infections occurred more frequently in overweight patients compared to the other BMI groups. In conclusion, overweight children with severe aplastic anemia have a higher risk of death after HCT independent of other factors analyzed in the study.BMI percentileN100 day mortality Probability (95% CI)2-y OS Probability (95% CI)RR of death (95% CI)p26-75th152515 (10-20)76 (70-82)1.00-<5th10812 ( 7-19)77 (68-84)1.01 (0.65-1.57)0.975-25th19611 ( 9-14)77 (74-81)1.38 (0.99-1.91)0.0676-95th30417 (13-21)73 (68-78)1.22 (0.93-1.61)0.14>95th14229 (22-36)59 (51-67)1.71 (1.24-2.35)0.0011Baseline group Disclosures: No relevant conflicts of interest to declare.

scholarly journals Alternative donor hematopoietic cell transplantation for Fanconi anemia

Blood ◽  
2015 ◽  
Vol 125 (24) ◽  
pp. 3798-3804 ◽  
Author(s):  
Margaret L. MacMillan ◽  
Todd E. DeFor ◽  
Jo-Anne H. Young ◽  
Kathryn E. Dusenbery ◽  
Bruce R. Blazar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Transplantation ◽  
Fanconi Anemia ◽  
Hematopoietic Cell Transplantation ◽  
Opportunistic Infections ◽  
Bone Marrow Failure ◽  
Key Points ◽  
Alternative Donor ◽  
Matched Sibling ◽  
Standard Risk

Key Points With no prior opportunistic infections/transfusions, 5-year survival after alternative donor HCT with TBI 300 cGy, CY, FLU, and ATG was 94%. Today, most FA patients with standard risk disease are cured of their bone marrow failure by HCT even without an HLA-matched sibling donor.

scholarly journals A Novel Protocol Decreased Incidence of Hepatic Veno-Occlusive Disease and Improved Results in Hematopoietic Cell Transplantation for Patients with b-Thalassemia Major

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5858-5858
Author(s):  
Chunfu Li ◽  
Fuyu Pei ◽  
Qi Li ◽  
Jianyun Liao ◽  
Shengli An ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Thalassemia Major ◽  
Occlusive Disease ◽  
Hematopoietic Cell ◽  
Common Complication ◽  
Alternative Donor ◽  
Matched Sibling ◽  
D Dimer

Abstract Hepatic veno-occlusive disease (VOD) is a common complication of hematopoietic cell transplantation (HCT), especially patients with β-thalassemia major (TM). To estimate whether incidence of VOD recently decreased after using NF-08-TM protocol (NP), 311 TM-HCTs performed from February 2003 to June 2013 were analyzed. 241 patients received NP in or after 2009 and 70 received non-NP before 2009. VOD was diagnosed by Seattle criteria (SC) or Baltimore Criteria (BC). Patients were stratified by Nanfang (NF) criteria. A total of 31(10.0%) and 14 (4.5%) HCTs developed VOD (6 and 5 developed severe VOD) in SC and BC cohorts, respectively. The incidence of VOD was significantly lower in NP versus non-NP groups and in Class 2 versus Class 3 groups. Overall survival was significantly higher in NP versus non-NP cohorts. Rate of VOD in alternative donor transplant (ADT) was similar to that in matched sibling transplant (MST). Requirement of platelet and value of D-dimer significantly increased in the VOD patients. Our study showed the incidence of VOD significantly decreased in our center after using NP. ADT was similar to MST on rate of VOD. NF criteria of stratification can indicate occurrence of VOD. The SC can be more suitable criteria for early diagnosis. Disclosures No relevant conflicts of interest to declare.

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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