Impact of Conditionning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Children with Acute Myeloid Leukemia in First Complete Remission: Total-Body Irradiation and Cyclophosphamide Versus Busulfan and Cyclophosphamide - A Report from The Societe Francaise de Greffe de Moelle et de Therapie Cellulaire.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 617-617 ◽  
Author(s):  
Jean-Hugues Dalle ◽  
Luc Caty ◽  
Regis Peffault ◽  
Alexandra Salmon ◽  
Valerie Mialou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Hematopoietic Stem

Abstract Goal: Compare results after allogeneic HSCT for AML in CR1 in pediatric population after myeloablative conditioning regimen either based on TBI or busulfan. Patients and Methods: Retrospective analysis from French registry including all consecutive patients under 18 years of age (n=131) from Dec’1979 and Oct’2004 transplanted for AML in CR1 with either sibling (n=104) or matched unrelated donor and given either multi-fractionated TBI 12Gy and cyclophosphamide 120mg/kg (TBI-Cy) or Busulfan 16mg/kg and Cyclophosphamide 200mg/kg (BuCy200). Results were analysed according to EBMT statistical analysis guidelines i.e. OS and EFS were analyzed by KM method and Log-rank test for comparison where TRM and relapse incidence were analyzed by cumulative incidence method and Gray test for comparison. Multivariate analyses were performed using proportional hazard model for the distribution of competitive risks defined by Fine and Gray. Results: 131 patients (female: 51.5%) were included. Median age at initial diagnosis was 11y (0.5 to 17.8). Median time from diagnosis to transplantation was 4.2 months. Eighty-three patients received BuCy200 and 48 patients were transplanted after TBI-Cy. Patient subgroups were comparable for age, gender, sex mismatch, source of graft (BMT vs PBSC), donor type (geno-identical vs 10/10 matched unrelated donor vs other), cytogenetical analysis and WBC at initial diagnosis, and for donor-recipient CMV status (−/+ vs others). Both 5 year-overall and event-free survival rates appeared significantly better in BuCy200 group than in TBI-Cy group with 73.3% vs 56.1% (p=0.02) and 67+/−7% vs 38+/−9% (p=0.002), respectively. TRM incidence at day 365 was dramatically better in BuCy200 group than in TBI-Cy group with 4,7% vs 26.1% of TRM rate (p=0.002), respectively. Even though there were no statistical significant differences for both acute and chronic GVHD cumulative incidences whatever given conditioning regimen, there was a trend for obtaining lesser GVHD in BuCy200 group: day 100 grade II-IV aGVHD cumulative incidence was 13% vs 37% and 2 year extensive cGVHD was 9 vs 19% for BuCy200 and TBI-Cy group, respectively. At 5 years, there was a trend for less relapse in BuCy200 group than in TBI-Cy 16+/−3% vs 32+/−6% (p=0.09), respectively. Conclusion: This study demonstrates the superiority of BuCy200 on TBI-Cy conditioning regimen for paediatric patients presenting with AML in CR1 and undergoing allogeneic hematopoietic stem cell transplantation from either matched related or unrelated donor. These results, obtained from a larger cohort, confirm and update those published by our group in 1994. Figure 1: Overall survival Figure 1:. Overall survival

Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Eugenia Piras ◽  
Adriana Vacca ◽  
Giovanna Giorgiani ◽  
Marco Zecca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

scholarly journals Infectious Complications Following Hematopoietic Stem Cell Transplantation Based on Fludarabine and Busulfan for Pediatric β-Thalassemia Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5880-5880
Author(s):  
Yanjun Xu ◽  
Chunfu Li ◽  
Yuelin He ◽  
Tiantian Yi ◽  
Jianyun Wen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Effective Measure

Abstract Background : Fludarabine and busulfan as a reduced-toxicity Conditioning regimen has been widely used for hematopoietic stem cell transplantation(HSCT) in pediatric β-thalassemia patients,however,the data of transplant-related infections in this population are scare. Methods:This retrospective study assessed the clinical features of infections in 265 children who received HSCT in pediatric department of Nanfang Hospital from January 2011 to December 2015,including 151 with allogeneic hematopoietic stem cell transplantation(allo-HSCT) from unrelated donors(UDs) who are all well-matched human leukocyte antigens, 87 with HSCT from matched sibling donors(MSDs),27 with genetic haploid transplantations from matched donors(father donors=13,mother donors=13,aunt donor=1). the median age was 6 years(range:1.7 to 16 years),and the ratio of male to female patients was 1.6(163:102).The median follow-up time was 35 months(range:8-68 months). Results: The cumulative incidence of neutrophil recovery was 97.70%,98.01% and 100% in MSD-HSCT,UD-PBSCT and genetic haploid,respectively.Most of the infections took place in the oral cavity(58.72%),respiratory tract, digestive tract and skin.Bacteremia developed in 46(17.36%) patients and 67.39% happened within 30 day of transplantation,the median time was +3 day(rang-2 to +11) when Bone marrow is barren period. G_ bacteria(68%) were the most commom causes of infections;Escherichia coli,Klebsiella pneumoniae and Pseudomonas aeruginosa accounted for the most of G- bacteria infections.Fungal turn out in 16(6.04%) patients,25% of the people was diagnosed with a probable,invasive fungal disease.The cumulative incidence of cytomegalovirus(CMV) and herpes zoster was 4.9% and17.36% .The cumulative incidence of grade II-IV aGVHD was 4.26%.17 patients died,9 of them suffered GVHD and complicated with severe pneumonia, 3 due to infection complicated with heart failure,4 of them were attributed to severe infections lead to multiple organ failure,and one appeared pancytopenia 6 months after transplantation , combined EB virus infection, cytomegalovirus infection, However, the use of MabThera treatment ineffective ,he died of liver failure,and brain hemorrhage.The estimate 5-year overall survival were 95%,94% and 84% in MSD-HSCT,UD-PBSCT and genetic haploid,respectively. Conclusions:In conclussion,our data suggests that the myeloablative conditioning regimen transplantation based on fludarabine and busulfan provided an effective measure for pediatric β-thalassemia patients with infections comparable to other transplant center reports but higher overall survival and disease free survival. More efforts should be made to rational use of antimicrobial drugs, empirical antifungal agents and strengthen the mouth, lungs, anus and other vulnerable parts of the care ,especially after the transplant neutropenic period. Disclosures No relevant conflicts of interest to declare.

scholarly journals Matched unrelated donor hematopoietic stem cell transplantation - our results

2017 ◽  
Vol 70 (suppl. 1) ◽  
pp. 63-65
Author(s):  
Marija Elez ◽  
Lavinika Atanaskovic ◽  
Svetlana Mirosavljevic ◽  
Gordana Ostojic ◽  
Biljana Todoric-Zivanovic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Myeloid Leukemia ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Hematopoietic Stem

Introduction. Allogeneic stem-cell transplantation is only potentially curative therapy for variety of hematology malignancies, such as acute and chronic leukemia, myelodisplastic syndrome and aplastic anemia, but also promising treatment option for other disorders. If we know that only 25% of patients have an human leukocyte antigen identical sibling donor, it is obvious that matched unrelated donor hematopoietic stem cell transplantation is an alternative for the rest of the patients. Material and Methods. Since 2013, matched unrelated donor hematopoietic stem cell transplantation has been performed routinely in the Military Medical Academy. Results. We hereby present the outcome after 77 procedures in 75 patients. Considering primary diseases, 35 patients had acute myeloid leukemia, 25 patients had acute lymphoid leukemia, 5 patients had chronic myeloid leukemia, 9 patients had myelodisplastic syndrome and we performed the transplant on 1 patient with chronic lymphocyte leukemia, 1 patient with aplastic anemia and 1 patient with T lymphoblastic lymphoma. Conclusion. It is difficult to make clear conclusions based on this heterogeneous group of patients, but it seems that these results are encouraging. Future research will be performed to evaluate matched unrelated donor and identical sibling hematopoietic stem cell transplantation in the homogenous groups with respect to primary diseases.

Impact of Cytogenetics on Outcome of Mismatched Unrelated Donor Hematopoietic Stem Cell Transplantation for Adults with AML.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 830-830 ◽  
Author(s):  
Martin Tallman ◽  
Gordon Dewald ◽  
Hillard Lazarus ◽  
Sharavi Gandham ◽  
Gene Nelson ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Kaplan Meier

Abstract Matched unrelated donor hematopoietic stem cell transplantation (MUD HSCT) is a potentially curative treatment for patients with acute myeloid leukemia (AML). The graft-versus-leukemia (GVL) effect may be potent enough to overcome the otherwise poor prognosis associated with AML though its efficacy for high risk cytogenetic subgroups is uncertain. To test this hypothesis, we analyzed outcomes by cytogenetic risk group in 324 patients in first complete remission (CR1), and 440 in CR2 undergoing NMDP-facilitated MUD HSCT between 1988–2002. Using the SWOG/ECOG classification of cytogenetic risk groups (Slovak et al. Blood, 2000) cytogenetics were classified as favorable in 14% of patients, intermediate in 71% and unfavorable in 16%. 56% of the patients were male and 42% were > 35 years at HSCT. 76% of patients and donors were matched at HLA-A, -B and -DRB1, 17% were mismatched at one or more loci and 7% were potentially matched (serologically matched at HLA-A and -B and potentially allele matched at -DR). Disease Status N Kaplan-Meier Estimate for Survival at 5 years Kaplan-Meier Estimate for Disease-Free Survival at 5 years Cumulative Incidence for 100 Day Transplant-Related Mortality Cumulative Incidence for Relapse at 5 years * p-value indeterminate; ** p=0.01 CR1 324 32 ± 6% 32 ± 5% 32 ± 5% 18 ± 4%     Intermediate 227 33 ± 7% 32 ± 7% 31 ± 6% 16 ± 5%*     Unfavorable 85 31 ± 11% 31 ± 10% 29 ± 10% 23 ± 9%* CR2 440 36 ± 5% 35 ± 5% 25 ± 4% 16 ± 3%     Favorable 93 46 ± 10% 44 ± 10% 25 ± 9% 10 ± 6%**     Intermediate 313 33 ± 6% 32 ± 5% 27 ± 5% 16 ± 4%**     Unfavorable 34 37 ± 17% 38 ± 16% 15 ± 12% 32 ± 15%** These data suggest that with the exception of the 5-year relapse rate, results of cytogenetics have little apparent influence on the outcome for patients undergoing MUD HSCT for AML in CR1. In CR2, results in patients with favorable cytogenetics appear to be better than those with intermediate or unfavorable cytogenetics, but are not statistically significantly different. Effective GVL and protection against relapse is observed, even in high risk cytogenetic subgroups. In this retrospective study, other prognostic factors may influence the outcome, but overall survival for patients with unfavorable cytogenetics appears at least as good as previously reported for matched sibling HSCT.

Favorable Outcome Of Hematopoietic Stem Cell Transplantation Using a Targeted Once-Daily IV Busulfan Fludarabine Etoposide Regimen In Pediatric and Infant ALL Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4553-4553
Author(s):  
Hyoung Jin Kang ◽  
Ji Won Lee ◽  
Sung jin Kim ◽  
Seung Hwan Lee ◽  
Kyung-Sang Yu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Conditioning Regimen ◽  
Favorable Outcome ◽  
Hematopoietic Stem ◽  
Once Daily

Conditioning regimens for pediatric acute lymphoblastic leukemia (ALL) usually include total body irradiation (TBI), but TBI may result in serious sequelae such as growth impairment, endocrinologic and metabolic problem, and secondary malignancies. Busulfan based conditioning regimen with cyclophosphamide has been used as an alternative to TBI based regimen in many diseases including pediatric ALL. Etoposide has been widely used in hematopoietic stem cell transplantation (HSCT) for lymphoid and myeloid malignancy because of its anti-leukemic effect, and a conditioning regimen containing busulfan, cyclophosphamide and etoposide (BuCyVP) was used in many studies including pediatric patients. But, toxicities have been reported in some studies using BuCyVP regimen. Recently, a reduced toxicity myeloablative regimen using busulfan and fludarabine showed promising results. Also, therapeutic drug monitoring (TDM) and administration of targeted dose of busulfan has been recommended to improve the outcome of HSCT. In this study, we evaluated the outcome of HSCT using a targeted once-daily intravenous (IV) busulfan fludarabine etoposide (BuFluVP) regimen in pediatric and infant ALL. The conditioning regimen was composed of busulfan, fludarabine (40 mg/m2 once daily i.v. on days -8 ∼ -3) and etoposide (20 mg/kg once daily i.v. on days -4 ∼ -2). Busulfan (≥ 1 year-120 mg/m2 and < 1 year-80 mg/m2) was administered once daily as the first dose on day -8, and targeted dose of busulfan was used according to the TDM results on day -7 ∼ -5. A total of 33 patients were evaluated. Donor-type neutrophil engraftment was achieved in all patients. Veno-occlusive disease occurred in 5 (15.2%) patients, but all of them were successfully treated. Grade II-IV acute GVHD developed in 11 patients (grade 2 in 9 patients, grade 3 in 1 and grade 4 in 1 patient) and the cumulative incidence was 33.6%. Chronic GVHD developed in 3 patients (2 extensive and 1 limited). Three patients died of treatment-related mortality (TRM) and the cumulative incidence was 9.1%. The causes of TRM were adenoviral pneumonia in 1, respiratory syncytial viral (RSV) pneumonia in 1 and interstitial lung disease in 1 patient. Relapse occurred in 3 patients and cumulative incidence was 9.1%. Overall survival (OS) and event free survival (EFS) of all patients were 84.9% and 81.8%, respectively. EFS showed no difference according to the type of HSCT (77.8% in related BMT/PBSCT, 82.4% in unrelated BMT/PBSCT, and 85.7% in CBT, P=0.95). Eleven patients (33.3%) were infants at diagnosis, and OS of these patients was 81.8%. Our study demonstrated that HSCT using a targeted once-daily IV BuFluVP regimen showed favorable outcome and could be one option for HSCT in pediatric and infant ALL. Disclosures: No relevant conflicts of interest to declare.

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