Graft versus leukemia effect against juvenile myelomonocytic leukemia after unrelated cord blood transplantation

2008 ◽  
Vol 50 (3) ◽  
pp. 665-667 ◽  
Author(s):  
Reo Tanoshima ◽  
Hiroaki Goto ◽  
Masakatsu Yanagimachi ◽  
Ryosuke Kajiwara ◽  
Fumiko Kuroki ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Juvenile Myelomonocytic Leukemia ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Graft Versus Leukemia ◽  
Unrelated Cord Blood ◽  
Myelomonocytic Leukemia ◽  
Graft Versus Leukemia Effect

Analysis of Risk Factors Influencing Outcomes After Unrelated Cord Blood Transplantation In Children with Juvenile Myelomonocytic Leukemia. An Eurocord, EBMT, EWOG-MDS, CIBMTR Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 533-533
Author(s):  
Alessandro Crotta ◽  
Vanderson Rocha ◽  
Mary Eapen ◽  
John E. Wagner ◽  
Margaret L. MacMillan ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Juvenile Myelomonocytic Leukemia ◽  
Advisory Committees ◽  
Monosomy 7 ◽  
Factors Associated ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Myelomonocytic Leukemia

Abstract Abstract 533 Juvenile myelomonocytic leukemia (JMML) is a rare and lethal myeloproliferative disease of young childhood. Currently, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment option. DFS at 5 years after HLA identical and unrelated HSCT was 55% (n=48) and 49% (n=52) in a largest series of patients published so far and mainly transplanted with bone marrow cells. Unrelated Cord Blood Transplantation (UCBT) is considered an alternative option for patients who lack an HLA-matched donor. We retrospectively analyzed 110 children, given a first single unmanipulated UCBT, from 1995 to 2010, and reported to Eurocord-EBMT and CIBMTR. Median age was 1 year (range 0.08–6.4) at diagnosis and 2 years (0.5-7.5) at transplantation, respectively. Median time interval between diagnosis and UCBT was 6 months (1-58); before transplantation, 88 patients were treated with low- or high-dose chemotherapy and splenectomy was performed in 24 children. Among 100 patients with available cytogenetic data, monosomy of chromosome 7 was the most frequent abnormality (24%). All but 8 patients received a myeloablative conditioning, Busulfan-Cyclophosphamide-Melphalan (BuCyMel) was used in 48 patients, total body irradiation (TBI) and Cyclophosphamide in 19 patients and combination of Busulfan-Cyclophosphamide with other drugs in 21 patients. Cyclosporin+steroid was the most common graft-versus-host disease (GvHD) prophylaxis (80%) and ATG was added in 86% of patients. Nineteen percent of units were HLA-identical (antigen level for HLA-A and B, allelic for DRB1), while 43% and 38% had 1 or 2–3 mismatches, respectively. Median TNC infused was 7.1×10e7/kg (1.7-27.6). Median follow-up was 44 months (3-169). At 60 days, cumulative incidence (CI) of neutrophil (PMN) recovery was 80±4%, with a median time to PMN recovery of 25 days. Grades II-IV acute GvHD developed in 45 patients, 100 days-CI of grade II-IV aGvHD was 40±5%. Among 90 patients at risk, 17 developed chronic GvHD and 4 years-CI was 16±4%. At 4 years CI of relapse was 37±5% (n=38); age older than 1 year at diagnosis was the only independent factor associated with increased risk of relapse (HR 2.3, p=0.038). Of note, among 58 patients with available data for level of fetal hemoglobin (HbF), a higher level of HbF (>35%) seemed to be associated with increased relapse incidence (57% versus 31% for remainders; p=0.05). At 4 years, DFS was 43±5%, in multivariate analysis independent factors associated with better DFS were: age younger than 1 year at diagnosis (53% vs 30%, HR 2.4, p=0.001), graft with 0 or 1 HLA mismatched cord blood unit (48% vs 34%, HR=2.1, p=0.006) and cytogenetic without monosomy 7 (48% vs 26%; HR=1.95, p=0.027). At 4 years, CI of transplant related mortality (TRM) was 20±4%; in multivariate analysis, cytogenetic with monosomy 7 (HR=2.7, p=0.036) and transplantation performed before 2003 (HR=3.7, p=0.015) were factors associated with increased TRM. In fact, CI of TRM was 14% after 2003 compared to 30% before 2003. Estimated overall survival (OS) at 4 years was 51±5%, and in multivariate analysis factors associated with decreased OS were: age older than 1 year at diagnosis (42% vs 60%; HR=2.03, p=0.032), and cytogenetic with monosomy 7, (30% vs 57%; HR=2.6, p=0.004). Fifty-one patients died after transplant, 53% for relapse and 47% for transplant related causes. In conclusion, UCBT may cure approximately 50% of patients with JMML who lack a matched related donor. Presence of monosomy 7 is associated with decreased DFS and increased TRM, independent of other factors. Other patient- (age at diagnosis) and transplantation-related factors (HLA and year of transplantation) were also associated with outcomes. Disease recurrence remains the major cause of treatment failure, and strategies to reduce the risk of relapse are warranted. Disclosures: Wagner: CORD:USE: Membership on an entity's Board of Directors or advisory committees; VidaCord: Membership on an entity's Board of Directors or advisory committees.

Unrelated Cord Blood Transplantation for Children with Juvenile Myelomonocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2021-2021
Author(s):  
Franco Locatelli ◽  
Adrienne B.M. Madureira ◽  
Vanderson Rocha ◽  
Pierre Teira ◽  
Martin Champagne ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Juvenile Myelomonocytic Leukemia ◽  
Monosomy 7 ◽  
Free Survival ◽  
Graft Versus Host ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Myelomonocytic Leukemia

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for children with juvenile myelomonocytic leukemia (JMML). A recent study from the European Working Group of MDS in Childhood (EWOG-MDS) reported a 5-year probability of event free survival of 55% (n=48), and 49% (n=52) in children transplanted from either an HLA identical sibling or an unrelated volunteer, mainly donating bone marrow (BM) cells. As in the EWOG-MDS analysis only 7 children received unrelated cord blood transplantation (UCBT), we decided to further investigate the role of UCBT in 42 children with JMML, reported to the Eurocord-EBMT and EWOG-MDS registries. Median age at transplantation of the 42 children was 2.6 years (range 0.6–7); 29 patients were males and 13 females. Cytogenetic analysis was available in all patients but one: 10 patients had monosomy 7, 4 other abnormalities, while the remaining 27 children had a normal karyotype. Seven patients underwent splenectomy before UCBT. Conditioning included Busulfan in 78% of patients, while the most common graft-versus-host disease (GVHD) prophylaxis consisted of Cyclosporin-A and steroids. In donor-recipient pairs, histocompatibility was determined by serology or low resolution molecular typing for HLA-A and -B antigens and by high-resolution DNA typing for DRB1 locus. The donor was HLA identical in 7 cases, 1-antigen disparate in 18 and with 2 or more disparities in 14. Median number of nucleated cells infused was 6.8 × 107/Kg (range 2–50). The 60-day cumulative incidence (CI) of engraftment was 76%%, with a median time to neutrophil and platelet recovery of 27 (range 14–51) and 50 (range 15–180) days, respectively. In multivariate analysis an age at UCBT younger than 2.6 years (hazard ratio, HR=0.27; 95% confidence interval=0.13–0.57; p=0.0005) and the use of a more HLA-compatible donor (HR=0.38; 95% confidence interval=0.16–0.89; p=0.03) predicted better engraftment. CI of grade II-IV acute and chronic graft-versus-host disease (GvHD), and of transplantation-related mortality (TRM) were 31%, 16%, and 33%, respectively. The CI of TRM of our cohort of patients is higher than the 2-year TRM CI of 16% in children with JMML given unrelated donor HSCT reported in the EWOG-MDS analysis. Eleven children relapsed, the 2-year CI of relapse being 22%. In comparison, in the EWOG-MDS study, the 2-year CI of relapse of unrelated HSCT recipients was 36%. The CI of relapse was 30% in patients with monosomy 7 as compared to 19% in the remaining children (p=0.64). With a median follow-up of 36 months (range 3–102), the 2-year disease-free survival (DFS) of the overall cohort was 45%; patients younger or older than 2.6 years had a DFS of 66% and 26% respectively, p=0.01. In multivariate analysis, only age at UCBT was associated with increased DFS (HR=2.98; 95% confidence interval=1.21–7.34; p=0.02). These data indicate that UCBT is a suitable option for children with JMML lacking an HLA-compatible relative and suggest that the search for an unrelated cord blood unit be initiated simultaneously to that for unrelated BM donors. Cord blood offers the advantage of nearly immediate availability of stem cells and allows to perform HSCT even in the presence of donor HLA disparities.

scholarly journals Unrelated cord blood transplantation—a single Colombian hospital experience

2006 ◽  
Vol 12 (2) ◽  
pp. 38
Author(s):  
F. Cuéllar-Ambrosi ◽  
A. Quevedo-Vélez ◽  
J.I. Duque-Martelo ◽  
J. Cuervo-Sierra ◽  
M. Sarmiento-Maldonado ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Hospital Experience ◽  
Unrelated Cord Blood

Novel adopted immunotherapy for mixed chimerism after unrelated cord blood transplantation in Omenn syndrome

2005 ◽  
Vol 75 (5) ◽  
pp. 441-444 ◽  
Author(s):  
Daisuke Tomizawa ◽  
Yuki Aoki ◽  
Masayuki Nagasawa ◽  
Tomohiro Morio ◽  
Michiko Kajiwara ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Mixed Chimerism ◽  
Omenn Syndrome ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Unrelated Cord Blood
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