scholarly journals Treatment of Fanconi anemia patients using fludarabine and low-dose TBI, followed by unrelated donor hematopoietic cell transplantation

2010 ◽  
Vol 46 (4) ◽  
pp. 539-544 ◽  
Author(s):  
M S Thakar ◽  
P Kurre ◽  
R Storb ◽  
M Kletzel ◽  
H Frangoul ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Fanconi Anemia ◽  
Low Dose ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Unrelated Donor

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.

Efficacy of keratinocyte growth factor in prevention of oral mucositis in children undergoing allogeneic hematopoietic cell transplantation

2020 ◽  
Vol 51 (3) ◽  
pp. 172-178
Author(s):  
Natalia Bartoszewicz ◽  
Krzysztof Czyżewski ◽  
Robert Dębski ◽  
Anna Krenska ◽  
Ewa Demidowicz ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Transplantation ◽  
Oral Mucositis ◽  
Hematopoietic Cell Transplantation ◽  
Clinical Course ◽  
Keratinocyte Growth Factor ◽  
Supportive Therapy ◽  
Primary Objective ◽  
Hematopoietic Cell ◽  
Unrelated Donor

AbstractIntroductionOral mucositis is regarded by patients as one of the worst and debilitating complications of conditioning and hematopoietic cell transplantation (HCT). Prevention of mucositis is one of the priorities of supportive therapy during and after conditioning.ObjectivesThe primary objective of the study was the analysis of efficacy of keratinocyte growth factor (KGF, palifermin) used in prophylaxis of oral mucositis in patients undergoing allo-HCT. The secondary objectives of the study included the analysis of the influence of palifermin on clinical course of oral mucositis and early transplant outcomes, as well as analysis of the contraindications of palifermin in patients undergoing allo-HCT.Patients and methodsA total number of 253 allo-HCT performed between 2003 and 2018 in patients aged 0–19 years in a single center were analyzed. Overall, in 161 HCTs, palifermin was administered.ResultsPatients receiving KGF were transplanted earlier in the context of calendar year, and more often received ATG, mainly due to the higher rate of unrelated donor transplants. Allo-HCT patients who were administered palifermin had shorter time of mucositis (median: 9 vs. 13 days, p < 0.001), lower mucositis grade (median: 2° vs. 3°; p < 0.001), shorter period of total parenteral nutrition (median: 19 vs. 22 days; p = 0.018), and lower incidence of episodes of febrile neutropenia (median: 39.1% vs. 83.1%; p < 0.001).ConclusionsThe use of palifermin has decreased duration and severity of oral mucositis in children after allo-HCT. Palifermin is a safe and well-tolerated compound in children undergoing allo-HCT.

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