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Recent Advances in Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia

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Abstract

Hematopoietic stem cell transplantation has been an important treatment modality in the management of high-risk or relapsed childhood acute lymphoblastic leukemia. Analysis of its efficacy has been based mostly on stratification of patients by epidemiologic criteria such as disease status at transplantation, type of donor, and conditioning regimens used. The outcome has improved only marginally over the years, with the improvement attributable mainly to better supportive care. Leukemia recurrence remains a major cause of treatment failure. Recent investigations have focused on the biology of the underlying malignancy and on transplant alloreactivity. The results of these investigations may provide a better scientific approach to indications for transplantation, donor selection, and disease monitoring.

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References

Papers of particular interest, published recently, have been highlighted as:• Of importance •• Of major importance

  1. Nguyen K, Devidas M, Cheng S-C, et al.: Factors influencing survival after elapse from acute lymphoblastic leukemia: a Children’s Oncology Group study. Leukemia 2008, 22:2141–2150.

    Google Scholar 

  2. Tomblyn MB, Arora M, Baker KS, et al.: Myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia: analysis of graft sources and long-term outcome. J Clin Oncol 2009, 27:3634–3641.

    Article  PubMed  Google Scholar 

  3. Lynch MH, Petersen FB, Appelbaum FR, et al.: Phase II study of busulfan, cyclophosphamide, and fractionated total body irradiation as a preparatory regimen for allogeneic bone marrow transplantation in patients with advanced myeloid malignancies. Bone Marrow Transplant 1995, 15:59–64.

    PubMed  Google Scholar 

  4. Clift RA, Buckner CD, Appelbaum FR, et al.: Long-term follow-up of a randomized trial of two irradiation regimens for patients receiving allogeneic marrow transplants during first remission of acute myeloid leukemia. Blood 1998, 92:1455–1456.

    CAS  PubMed  Google Scholar 

  5. Cardoso AA, Schultze JL, Boussiotis VA, et al.: Pre-B acute lymphoblastic cells may induce T cell-anergy to alloantigens. Blood 1996, 88:41–48.

    CAS  PubMed  Google Scholar 

  6. Ruggeri L, Canpanni M, Urbani E, et al.: Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002, 295:2097–2110.

    Article  CAS  PubMed  Google Scholar 

  7. Satwani P, Sather H, Ozkaynak F, et al: Allogeneic bone marrow transplantation in first remission for children with ultra-high-risk features of acute lymphoblastic leukemia: a children’s Oncology Group study report. Biol Blood Marrow Transplant 2007, 13:218–227.

    Article  CAS  PubMed  Google Scholar 

  8. Schrauder A, Reiter A, Gadner H, et al.: Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol 2006, 24:5742–5749.

    Article  PubMed  Google Scholar 

  9. •• Schrauder A, von Stackelberg A, Schrappe M, et al.: Allogeneic hematopoietic SCT in children with ALL: current concepts of ongoing prospective SCT trials. Bone Marrow Transplant 2008, 41(suppl 1):S71–S74. This is a review from the Berlin-Frankfurt-Münster (BFM) Group of indications for hematopoietic stem cell transplantation.

    Article  PubMed  Google Scholar 

  10. Mullighan CG, Zhang J, Harvey RC, et al.: JAK mutations in high-risk childhood lymphoblastic leukemia. Proc Natl Acad Sci USA 2009, 106:9414–9418.

    Article  CAS  PubMed  Google Scholar 

  11. Coustan-Smith E, Mullighan CG, Onciu M, et al.: Early T-cell precursor leukemia: a subtype of very high-risk acute lymphoblastic leukemia. Lancet Oncol 2009, 10:147–156.

    Article  CAS  PubMed  Google Scholar 

  12. Nachman JB, Heerema NA, Sather HN, et al.: Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Blood 2007, 110:1112–1115.

    Article  CAS  PubMed  Google Scholar 

  13. Pieters R, Schrappe M, DeLorenzo P, et al.: A treatment protocol for infants younger than 1 year with acute lymphoblastic leukemia (Interfant 99): an observational study and a multicentre randomized trial. Lancet 2007, 370:240–250.

    Article  CAS  PubMed  Google Scholar 

  14. Tomizawa D, Koh K, Sato T, et al.: Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group. Leukemia 2007, 21:2258–2263.

    Article  CAS  PubMed  Google Scholar 

  15. Van der Velden VHJ, Corral L, Valsecchi MG, et al.: Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated with the Interfant-99 protocol. Leukemia 2009, 23:1073–1079.

    Article  PubMed  Google Scholar 

  16. •• Schultz KR, Bowman WP, Aledo A, et al.: Improved early event-free survival with imatinib in Philadelphia chromosome–positive acute lymphoblastic leukemia: a Children’s Oncology Group study. J Clin Oncol 2009, 21:5175–5181. This is the first report showing that a TKI and chemotherapy may produce outcomes similar to those of allogeneic stem cell transplantation in Philadelphia chromosome–positive ALL in children.

    Article  Google Scholar 

  17. Burke MJ, Cao Q, Tortz B, et al.: Allogeneic hematopoietic cell transplantation for treatment of pediatric Philadelphia chromosome–positive acute lymphoblastic leukemia. Pediatr Blood Cancer 2009, 53:1289–1294.

    Article  PubMed  Google Scholar 

  18. Eapen M, Zhang MJ, Devidas M, et al.: Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after isolated central nervous system relapse: a collaborative study of the Children’s Oncology Group and the Center for International Blood and Marrow Transplant Research. Leukemia 2008, 22:281–286.

    Article  CAS  PubMed  Google Scholar 

  19. Harker-Murray PD, Thomas AJ, Wagner JE, et al.: Allogeneic hematopoietic cell transplantation in children with relapsed acute lymphoblastic leukemia isolated to the central nervous system. Biol Blood Marrow Transplant 2008, 14:685–689.

    Article  CAS  PubMed  Google Scholar 

  20. • Davies SM, Wang D, Wang T, et al.: Recent decrease in acute graft-versus-host disease in children with leukemia receiving unrelated donor bone marrow transplants. Biol Blood Marrow Transplant 2009, 15:360–366. This study included large numbers of children with ALL and confirmed the presence of the GvL effect in this diagnosis.

    Article  PubMed  Google Scholar 

  21. Eapen M, Rubinstein P, Zhang M-J, et al.: Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukemia: a comparison study. Lancet 2007, 369:1947–1954.

    Article  PubMed  Google Scholar 

  22. Kurtzberg J, Prasad VK, Carter SL, et al.: Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies. Blood 2008, 112:4318–4327.

    Article  CAS  PubMed  Google Scholar 

  23. • Vermeris MR, Brunstein CG, Barker J, et al.: Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units. Blood 2009, 114:4293–4299. A lower risk of relapse was reported in standard-risk leukemia patients receiving double cord blood transplants. If confirmed, this finding may affect the future cord blood selection process.

    Article  Google Scholar 

  24. Gutman JA, Leisenring W, Appelbaum FR, et al.: Low mortality without excessive transplant-related mortality following myeloablative cord blood transplantation for acute leukemia in complete remission: a matched cohort analysis. Biol Blood Marrow Transplant 2009, 15:1122–1129.

    Article  CAS  PubMed  Google Scholar 

  25. •• Willemze R, Rodrigues CA, Labopin M, et al.: KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia. Leukemia 2009, 23:492–500. This is the first report to explore KIR-ligand incompatibility in cord blood transplants. The result may have significant implications for the future cord blood unit selection process.

    Article  CAS  PubMed  Google Scholar 

  26. Pende D, Marcenaro S, Falco M, et al.: Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. Blood 2009, 113:3119–3129.

    Article  CAS  PubMed  Google Scholar 

  27. Pfeiffer M, Schumm M, Feuchtinger T, et al.: Intensity of HLA class I expression and KIR-mismatch determine NK-cell mediated lysis of leukemic blasts from children with acute lymphoblastic leukemia. Brit J Haematol 2007, 138:97–100.

    Article  Google Scholar 

  28. Eapen M, Raetz E, Zhang MJ, et al.: Outcomes of HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of Children’s Oncology Group and the Center for International Blood and Marrow Transplant Research. Blood 2006, 107:4961–4967.

    Article  CAS  PubMed  Google Scholar 

  29. Willemze AJ, Geskus RB, Noordijk EM, et al.: HLA-identical haematopoietic stem cell transplantation for acute lymphoblastic leukemia in children: less relapse with higher biologically effective dose of TBI. Bone Marrow Transplant 2007, 40:319–327.

    Article  CAS  PubMed  Google Scholar 

  30. Marks DI, Forman SJ, Blume KG, et al.: A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biol Blood Marrow Transplant 2006, 12:438–453.

    Article  CAS  PubMed  Google Scholar 

  31. Pulsipher MA, Boucher KM, Wall D, et al.: Reduced-intensity allogeneic transplantation in pediatric patients ineligible for myeloablative therapy: results of the Pediatric Blood and Marrow Transplant Consortium Study ONC0313. Blood 2009, 114:1429–1436.

    Article  CAS  PubMed  Google Scholar 

  32. Perez A, Gonzalez-Vicent M, Ramirez M, et al.: Intentional induction of mixed haematopoietic chimerism as platform for cellular therapy after HLA-matched allogeneic stem cell transplantation in childhood leukemia patients. Brit J Haematol 2007, 140:340–343.

    Article  Google Scholar 

  33. Campana D: Role of minimal residual disease monitoring in adult and pediatric acute lymphoblastic leukemia. Hematol Oncol Clin N Am 2009, 23:1083–1098.

    Article  Google Scholar 

  34. Knethti CJ, Goulden NJ, Hancock JP, et al.: Minimal residual disease status as a predictor of relapse after allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia. Brit J Haematol 1998, 102:860–871.

    Article  Google Scholar 

  35. Van der Velden VH, Joosten SA, Willemse MJ, et al.: Real-time quantitative PCR for detection of minimal residual disease before allogeneic stem cell transplantation predicts outcome in children with acute lymphoblastic leukemia, Leukemia 2001, 15:1485–1487.

    Article  PubMed  Google Scholar 

  36. Bader P, Hancock J, Kreyenberg H, et al.: Minimal residual disease status prior to allogeneic stem cell transplantation is a powerful predictor for post-transplant outcome in children with ALL. Leukemia 2002, 16:1668–1672.

    Article  CAS  PubMed  Google Scholar 

  37. •• Bader P, Kreyenberg H, Henze GHR, et al.: Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: The ALL-REZ BFM Study Group. Cancer 2009, 27:377–384. In this prospective study, MRD was the only significant prognostic factor in children with relapsed ALL undergoing stem cell transplantation.

    Google Scholar 

  38. Sramkova L, Muzikova K, Fronkova E, et al.: Detectable minimal residual disease before allogeneic hematopoietic stem cell transplantation predicts extremely poor prognosis in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 2007, 48:93–100.

    Article  PubMed  Google Scholar 

  39. •• Paganin M, Zecca M, Fabbri G, et al.: Minimal residual disease is an important predictive factor of outcome in children with relapsed ‘high-risk’ acute lymphoblastic leukemia. Leukemia 2008, 22:2193–2200. This study showed that early determination of MRD has prognostic significance and suggested that alternative treatment should be employed in the MRD-positive cases

    Article  CAS  PubMed  Google Scholar 

  40. Spinelli O, Peruta B, Tosi M, et al.: Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of clinical outcome of adult patients with high-risk acute lymphoblastic leukemia. Haematologica 2007, 92:612–618.

    Article  PubMed  Google Scholar 

  41. Irving J, Jesson J, Virgo P, et al.: Establishment and validation of a standard protocol for the detection of minimal residual disease in B lineage childhood acute lymphoblastic leukemia by flow cytometry in a multi-center setting. Haematologia 2009, 94:870–874.

    Article  Google Scholar 

  42. Ishaqi MK, Afzal S, Dupuis A, et al.: Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft-versus-host disease in pediatric acute lymphoblastic leukemia. Bone Marrow Transplant 2007, 13:1216–1223.

    Google Scholar 

  43. • Koehl U, Bochennek K, Zimmermann SY, et al.: Immune recovery in children undergoing allogeneic stem cell transplantation: absolute CD8CD3 count reconstitution is associated with survival. Bone Marrow Transplant 2007, 39:269–278. This study prospectively followed the pattern recovery of NK cells, lymphocytes, and their subpopulation after HSCT in children.

    Article  CAS  PubMed  Google Scholar 

  44. Kodder KT, Henslee-Downey PJ, Mehta J, et al.: Long-term disease-free survival in acute leukemia patients recovering with increased γδ T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transplant 2007, 39:751–757.

    Google Scholar 

  45. Nakamura R, Auayporn N, Smith DD, et al.: Impact of graft cell dose on transplant outcomes following unrelated donor allogeneic peripheral blood stem cell transplantation: higher CD34+ cell doses are associated with decreased relapse rates. Biol Blood Marrow Transplant 2008, 14:449–457.

    Article  CAS  PubMed  Google Scholar 

  46. Rezvani K, Yong AS, Savani BN, et al.: Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia. Blood 2007, 110:1924–1932.

    Article  CAS  PubMed  Google Scholar 

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  1. Pediatric Blood and Marrow Transplantation, Texas Transplant Institute, 4410 Medical Drive, Suite 550, San Antonio, TX, 78229, USA

    Veronica Jude & Ka Wah Chan

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  1. Veronica Jude
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  2. Ka Wah Chan
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Correspondence to Ka Wah Chan.

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Jude, V., Chan, K.W. Recent Advances in Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia. Curr Hematol Malig Rep 5, 129–134 (2010). https://doi.org/10.1007/s11899-010-0050-1

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