Abstract
We describe 70 children with myelodysplastic syndrome (MDS) (refractory cytopenia (n=31) and refractory anemia with excess blasts (n=30) or blasts in transformation (n=9)) who received umbilical cord blood (UCB) transplantation with a single UCB unit and a myeloablative conditioning regimen. Approximately 20% of children had secondary MDS. Median age at transplantation was 7 years and the median follow-up was 3 years. The day-60 probability of neutrophil recovery was 76%; recovery was faster after transplantation of matched or 1-locus mismatched UCB, irradiation-containing conditioning regimen, cell dose >6 × 107/kg and monosomy 7. Risks of treatment failure (recurrent disease or death) were lower in patients with monosomy 7 and transplantations after 2001. The 3-year disease-free survival (DFS) was 50% for transplantations after 2001 compared with 27% for the earlier period (P=0.018). Transplantations after 2001 occurred within 6 months after diagnosis and used UCB units with higher cell dose. DFS was highest in patients with monosomy 7 (61%) compared with other karyotypes (30%), P=0.017. These data suggest that transplantation of mismatched UCB graft is an acceptable alternative for children without a matched sibling or suitably matched unrelated adult donor.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Locatelli F, Zecca M, Pession A, Maserati E, De Stefano P, Severi F . Myelodysplastic syndromes: the pediatric point of view. Haematologica 1995; 80: 268–279.
Kardos G, Baumann I, Passmore SJ, Locatelli F, Hasle H, Schultz KR et al. Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7. Blood 2003; 102: 1997–2003.
Hasle H, Baumann I, Bergstrasser E, Fenu S, Fischer A, Kardos G et al. The International Prognostic Scoring System (IPSS) for childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML). Leukemia 2004; 18: 2008–2014.
Creutzig U, Bender-Gotze C, Ritter J, Zimmermann M, Stollmann-Gibbels B, Korholz D et al. The role of intensive AML-specific therapy in treatment of children with RAEB and RAEB-t. Leukemia 1998; 12: 652–659.
Guinan EC, Tarbell NJ, Tantravahi R, Weinstein HJ . Bone marrow transplantation for children with myelodysplastic syndromes. Blood 1989; 73: 619–622.
Hasle H, Kerndrup G, Yssing M, Clausen N, Ostergaard E, Jacobsen N et al. Intensive chemotherapy in childhood myelodysplastic syndrome. A comparison with results in acute myeloid leukemia. Leukemia 1996; 10: 1269–1273.
Locatelli F, Pession A, Bonetti F, Maserati E, Prete L, Pedrazzoli P et al. Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes. Leukemia 1994; 8: 844–849.
Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001; 97: 2962–2971.
Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369: 1947–1954.
Picardi A, Del Principe D, Cudillo L, Dentamaro T, Amadori S, de Fabritiis P . Unrelated cord blood transplantation for children with high risk myelodysplastic syndromes. Haematologica 2004; 89: ELT08.
Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia 2003; 17: 277–282.
Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.
Fine JP, Gray R . A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496–509.
Kaplan E . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.
Cox DR . Regression models and life tables. J R Stat Soc 1972; 34: 187.
Hasle H . Myelodysplastic and myeloproliferative disorders in children. Curr Opin Pediatr 2007; 19: 1–8.
Michel G, Rocha V, Chevret S, Arcese W, Chan KW, Filipovich A et al. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. Blood 2003; 102: 4290–4297.
Locatelli F, Rocha V, Chastang C, Arcese W, Michel G, Abecasis M et al. Factors associated with outcome after cord blood transplantation in children with acute leukemia. Eurocord-Cord Blood Transplant Group. Blood 1999; 93: 3662–3671.
Rocha V, Michel G, Kabbara N, Arcese W, Ortega J, Iori AP et al. Outcomes after unrelated cord blood transplantation in children with acute lymphoblastic leukemia: a Eurocord-Netcord survey (abstr# 304). Blood 2005; 106: 93a.
Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, McGlave PB, Miller JS et al. Transplantation of 2 partially HLA-matched umbilical cord blood units to enhance engraftment in adults with hematologic malignancy. Blood 2005; 105: 1343–1347.
Locatelli F, Zecca M, Niemeyer C, Angelucci E, Arcese G, Bender-Gotze C et al. Role of allogeneic bone marrow transplantation for the treatment of myelodysplastic syndromes in childhood. The European Working Group on Childhood Myelodysplastic Syndrome (EWOG-MDS) and the Austria–Germany–Italy (AGI) Bone Marrow Transplantation Registry. Bone Marrow Transplant 1996; 18 (Suppl 2): 63–68.
Yusuf U, Frangoul HA, Gooley TA, Woolfrey AE, Carpenter PA, Andrews RG et al. Allogeneic bone marrow transplantation in children with myelodysplastic syndrome or juvenile myelomonocytic leukemia: the Seattle experience. Bone Marrow Transplant 2004; 33: 805–814.
Davies SM, Wagner JE, Defor T, Blazar BR, Katsanis E, Kersey JH et al. Unrelated donor bone marrow transplantation for children and adolescents with aplastic anaemia or myelodysplasia. Br J Haematol 1997; 96: 749–756.
Webb DK, Passmore SJ, Hann IM, Harrison G, Wheatley K, Chessells JM . Results of treatment of children with refractory anaemia with excess blasts (RAEB) and RAEB in transformation (RAEBt) in Great Britain 1990–99. Br J Haematol 2002; 117: 33–39.
de Witte T, Pikkemaat F, Hermans J, van Biezen A, Mackinnan S, Cornelissen J et al. Genotypically nonidentical related donors for transplantation of patients with myelodysplastic syndromes: comparison with unrelated donor transplantation and autologous stem cell transplantation. Leukemia 2001; 15: 1878–1884.
Anderson JE, Appelbaum FR, Fisher LD, Schoch G, Shulman H, Anasetti C et al. Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. Blood 1993; 82: 677–681.
Hasle H, Arico M, Basso G, Biondi A, Cantu Rajnoldi A, Creutzig U et al. Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. European Working Group on MDS in Childhood (EWOG-MDS). Leukemia 1999; 13: 376–385.
Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW et al. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Exp Hematol 2004; 32: 397–407.
Borojevic R, Roela RA, Rodarte RS, Thiago LS, Pasini FS, Conti FM et al. Bone marrow stroma in childhood myelodysplastic syndrome: composition, ability to sustain hematopoiesis in vitro, and altered gene expression. Leuk Res 2004; 28: 831–844.
Aizawa S, Nakano M, Iwase O, Yaguchi M, Hiramoto M, Hoshi H et al. Bone marrow stroma from refractory anemia of myelodysplastic syndrome is defective in its ability to support normal CD34-positive cell proliferation and differentiation in vitro. Leuk Res 1999; 23: 239–246.
Migliaccio AR, Adamson JW, Stevens CE, Dobrila NL, Carrier CM, Rubinstein P . Cell dose and speed of engraftment in placental/umbilical cord blood transplantation: graft progenitor cell content is a better predictor than nucleated cell quantity. Blood 2000; 96: 2717–2722.
Wagner JE, Barker JN, DeFor TE, Baker KS, Blazar BR, Eide C et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 2002; 100: 1611–1618.
Parikh SH, Mendizabal A, Martin PL, Prasad VK, Szabolcs P, Driscoll TA et al. Unrelated donor umbilical cord blood transplantation in pediatric myelodysplastic syndrome: a single-center experience. Biol Blood Marrow Transplant 2009; 15: 948–955.
Trobaugh-Lotrario AD, Kletzel M, Quinones RR, McGavran L, Proytcheva MA, Hunger SP et al. Monosomy 7 associated with pediatric acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS): successful management by allogeneic hematopoietic stem cell transplant (HSCT). Bone Marrow Transplant 2005; 35: 143–149.
Strahm B, Locatelli F, Bader P, Ehlert K, Kremens B, Zintl F et al. Reduced intensity conditioning in unrelated donor transplantation for refractory cytopenia in childhood. Bone Marrow Transplant 2007; 40: 329–333.
Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood 2007; 110: 3064–3070.
Acknowledgements
This work was funded by Public Health Service Grant U24-CA 756518-11 (ME, M-JZ) from the National Cancer Institute, the National Institute of Allergy and Infectious Diseases and the National Heart Lung and Blood Institute and Inserm grant TGIR0805 (VR).
Author information
Authors and Affiliations
Consortia
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
These data were presented in part at the American Society of Hematology annual meeting, San Francisco, 2008.
Rights and permissions
About this article
Cite this article
Madureira, A., Eapen, M., Locatelli, F. et al. Analysis of risk factors influencing outcome in children with myelodysplastic syndrome after unrelated cord blood transplantation. Leukemia 25, 449–454 (2011). https://doi.org/10.1038/leu.2010.285
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/leu.2010.285
Keywords
This article is cited by
-
Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children
International Journal of Hematology (2022)
-
Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022
Bone Marrow Transplantation (2022)
-
Prognostic value of the revised International Prognostic Scoring System five-group cytogenetic abnormality classification for the outcome prediction of hematopoietic stem cell transplantation in pediatric myelodysplastic syndrome
Bone Marrow Transplantation (2021)
-
Graft-versus-MDS effect after unrelated cord blood transplantation: a retrospective analysis of 752 patients registered at the Japanese Data Center for Hematopoietic Cell Transplantation
Blood Cancer Journal (2019)
-
Increased opportunity for prolonged survival after allogeneic hematopoietic stem cell transplantation in patients aged 60–69 years with myelodysplastic syndrome
Annals of Hematology (2019)