Abstract
Management of relapsed acute lymphoblastic leukemia (ALL) is challenging and far from satisfactory. The treatment approaches are often varied and controversial. The duration of first remission, site of relapse, immunophenotypic and molecular characteristics of relapsed disease and response to therapy influence treatment outcome. There are three main therapeutic options i.e., chemotherapy alone, induction chemotherapy followed by HLA matched allogeneic transplant and palliation. These may be chosen based on the above mentioned factors. The response to therapy may be evaluated morphologically or by minimal residual disease (MRD). Persistence of MRD, as assessed by molecular techniques or through flowcytometry, clearly influences prognosis in children with relapsed ALL. It not only helps in identifying the subset of patients likely to benefit from allogeneic bone marrow transplant (ABMT) but also in determining the timing of transplant. Patients with non-T phenotype, with late relapsing disease and good response to re-induction therapy have been shown to do equally well with chemotherapy alone. On the other hand patients with early relapse and poor initial response are selected for ABMT. With the improvement in supportive care, better selection of HLA match donors and better immunosuppressive therapies, transplant related mortality has decreased considerably. Despite all of these overall salvage rates are still poor and novel agents are being tested in various trials to establish their role in relapsed ALL therapy.
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Tallen G, Ratei R, Mann G, et al. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: Results of trial ALL-REZ BFM 90. J Clin Oncol. 2010;28:2339–47.
Raetz EA, Borowitz MJ, Devidas M, et al. Reinduction platform for children with first marrow relapse of acute lymphoblastic leukemia: A children’s oncology group study [corrected]. J Clin Oncol. 2008;26:3971–8.
Möricke A, Zimmermann M, Reiter A, et al. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia. 2010;24:265–84.
Nguyen K, Devidas M, Cheng SC, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: A children’s oncology group study. Leukemia. 2008;22:2142–50.
Einsiedel HG, von Stackelberg A, Hartmann R, et al. Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: Results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Münster Group 87. J Clin Oncol. 2005;23:7942–50.
Lawson SE, Harrison G, Richards S, et al. The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: A report on the medical research council UKALLR1 study. Br J Haematol. 2000;108:531–43.
Gaynon PS, Qu RP, Chappell RJ, et al. Survival after relapse in childhood acute lymphoblastic leukemia: Impact of site and time to first relapse-the Children’s Cancer Group Experience. Cancer. 1998;82:1387–95.
Bader P, Kreyenberg H, Henze GH, 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. J Clin Oncol. 2009;27:377–84.
Sandowitz D, Smith SD, Shuster J, Wharam MD, Buchanan GR, Rivera GK. Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: A pediatric oncology group study. Blood. 1993;81:602–9.
Hijiya N, Gajjar A, Zhang Z, et al. Low-dose oral etoposide-based induction regimen for children with acute lymphoblastic leukemia in first bone marrow relapse. Leukemia. 2004;18:1581–6.
Parker C, Waters R, Leighton C, et al. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): An open-label randomised trial. Lancet. 2010;376:2009–17.
O’Connor D, Sibson K, Caswell M, et al. Early UK experience in the use of clofarabine in the treatment of relapsed and refractory paediatric acute lymphoblastic leukaemia. Br J Haematol. 2011;154:482–5.
Cohen MH, Johnson JR, Massie T, et al. Approval summary: Nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma. Clin Cancer Res. 2006;12:5329–35.
Dunsmore KP, Devidas M, Linda SB, et al. Pilot study of nelarabine in combination with intensive chemotherapy in high-risk T-cell acute lymphoblastic leukemia: A report from the Children’s Oncology Group. J Clin Oncol. 2012;30:2753–9.
Rivera GK, Hudson MM, Liu Q, et al. Effectiveness of intensified rotational combination chemotherapy for late hematologic relapse of childhood acute lymphoblastic leukemia. Blood. 1996;88:831–7.
Eapen M, Raetz E, Zhang MJ, et al. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: A collaborative study of the Children’s Oncology Group and the Center for International Blood and Marrow Transplant Research. Blood. 2006;107:4961–7.
Ritchey AK, Pollock BH, Lauer SJ, Andejeski Y, Barredo J, Buchanan GR. Improved survival of children with isolated CNS relapse of acute lymphoblastic leukemia: A pediatric oncology group study. J Clin Oncol. 1999;17:3745–52.
Barredo JC, Devidas M, Lauer SJ, et al. Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation: A pediatric oncology group study. J Clin Oncol. 2006;24:3142–9.
Boulad F, Steinherz P, Reyes B, et al. Allogeneic bone marrow transplantation versus chemotherapy for the treatment of childhood acute lymphoblastic leukemia in second remission: A single-institution study. J Clin Oncol. 1999;17:197–207.
Gaynon PS, Harris RE, Altman AJ, et al. Bone marrow transplantation versus prolonged intensive chemotherapy for children with acute lymphoblastic leukemia and an initial bone marrow relapse within 12 months of the completion of primary therapy: Children’s oncology group study CCG-1941. J Clin Oncol. 2006;24:3150–6.
Torres A, Alvarez MA, Sánchez J, et al. Allogeneic bone marrow transplantation vs chemotherapy for the treatment of childhood acute lymphoblastic leukaemia in second complete remission (revisited 10 years on). Bone Marrow Transplant. 1999;23:1257–60.
Bleakley M, Shaw PJ, Nielsen JM. Allogeneic bone marrow transplantation for childhood relapsed acute lymphoblastic leukemia: Comparison of outcome in patients with and without a matched family donor. Bone Marrow Transplant. 2002;30:1–7.
Wheeler K, Richards S, Bailey C, Chessells J. Comparison of bone marrow transplant and chemotherapy for relapsed childhood acute lymphoblastic leukaemia: The MRC UKALL X experience. Medical Research Council Working Party on Childhood Leukaemia. Br J Haematol. 1998;101:94–103.
Davies SM, Ramsay NK, Klein JP, et al. Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia. J Clin Oncol. 2000;18:340–7.
Bunin N, Aplenc R, Kamani N, et al. Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: A pediatric blood and marrow transplant consortium study. Bone Marrow Transplant. 2003;32:543–8.
Gassas A, Sung L, Saunders EF, Doyle JJ. Comparative outcome of hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia following cyclophosphamide and total body irradiation or VP16 and total body irradiation conditioning regimens. Bone Marrow Transplant. 2006;38:739–43.
Sanders JE. The impact of marrow transplant preparative regimens on subsequent growth and development. The seattle marrow transplant team. Semin Hematol. 1991;28:244–9.
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;112:4318–27.
Smith AR, Baker KS, Defor TE, Verneris MR, Wagner JE, Macmillan ML. Hematopoietic cell transplantation for children with acute lymphoblastic leukemia in second complete remission: Similar outcomes in recipients of unrelated marrow and umbilical cord blood versus marrow from HLA matched sibling donors. Biol Blood Marrow Transplant. 2009;15:1086–93.
Woolfrey AE, Anasetti C, Storer B, et al. Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children. Blood. 2002;99:2002–8.
Gassas A, Sung L, Saunders EF, Doyle J. Graft-versus-leukemia effect in hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia: Significantly lower relapse rate in unrelated transplantations. Bone Marrow Transplant. 2007;40:951–5.
Raetz EA, Cairo MS, Borowitz MJ, et al. Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: A Children’s Oncology Group Pilot Study. J Clin Oncol. 2008;26:3756–62.
Topp MS, Kufer P, Gökbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011;29:2493–8.
Ottmann O, Dombret H, Martinelli G, et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: Interim results of a phase 2 study. Blood. 2007;110:2309–15.
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Jain, S., Kapoor, G. How to Treat Relapsed Acute Lymphoblastic Leukemia: Transplant vs. Conventional Chemotherapy. Indian J Pediatr 80, 846–852 (2013). https://doi.org/10.1007/s12098-013-1036-5
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DOI: https://doi.org/10.1007/s12098-013-1036-5