Maintenance Immunotherapy by Repetitive Low-Dose Donor Lymphocytes Infusions in a Child With Relapse State Aml After Allogeneic Stem Cell Transplantation

Hartwig, Maite; Weigel, Steffen; Bernig, Toralf; Bader, Peter; Dölken, Regina; Beck, James F.

doi:10.1080/08880010601125443

Cited by 3 publications

(4 citation statements)

References 9 publications

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“…[19][20][21][22] In contrast to patients with chronic myeloid leukemia, in whom moderate doses of DLI were found to be effective, patients with AML required higher doses to achieve an antileukemic response 6,23 ; therefore, immunotherapy seems to be more effective in stages of impending, rather than frank, hematologic relapse. 6,23 Consequently, an early assessment of high-risk patients appears to be beneficial for successful immunotherapy after transplantation, allowing lower DLI doses than necessary to treat frank relapse.…”

Section: Discussionmentioning

confidence: 99%

Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing evidence of mixed chimerism after allogeneic stem cell transplantation

Rettinger

Willasch

Kreyenberg

et al. 2011

Blood

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Previous studies have shown that children with acute myeloid leukemia (AML) who developed mixed chimerism (MC) were at high risk for relapse after allogeneic stem-cell transplantation (allo-SCT). We investigated the feasibility of intensified preemptive immunotherapy in children receiving allo-SCT for AML. Eightyfour children were registered in our trial from May 2005 to April 2009; of these, 71 fulfilled the inclusion criteria and were treated according to the study protocol. Serial and semiquantitative analyses of posttransplantation chimerism were performed. Defined immunotherapy approaches were considered in MC patients. Continuous complete chimerism (CC) was observed in 51 of 71 patients. MC was detected in 20 patients and was followed by immunotherapy in 13. Six of 13 MC patients returned to CC without toxicity and remained in long-term remission. Overall, the probability of event-free survival (pEFS) was 66% (95% confidence interval [95% CI] ‫؍‬ 53%-76%) for all patients and 46% (95% CI ‫؍‬ 19%-70%) in MC patients with intervention; however, this number increased to 71% (95% CI ‫؍‬ 26%-92%) in 7 of 13 MC patients on immunotherapy who were in remission at the time of transplantation. All MC patients without intervention relapsed. These results suggest that MC is a prognostic factor for impending relapse in childhood AML, and that preemptive immunotherapy may improve the outcome in defined high-risk patients after transplantation. (Blood. 2011;118(20):5681-5688)

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Section: Discussionmentioning

confidence: 99%

Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing evidence of mixed chimerism after allogeneic stem cell transplantation

Rettinger

Willasch

Kreyenberg

et al. 2011

Blood

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“…In parallel with the usual prolonged maintenance therapy (up to 2 years) for newly diagnosed and relapsed ALL, it may likewise be necessary to provide continuing immunotherapeutic interventions for a prolonged period of time to eradicate residual leukemic cells. 50,51 These interventions may be combined with adjuvant therapy and/or supportive chemotherapy to prevent relapses in immuneprivileged sites. 52 …”

Section: Discussionmentioning

confidence: 99%

Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation

et al. 2010

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Relapse of pediatric acute lymphoblastic leukemia (ALL) remains the main cause of treatment failure after allogeneic stem cell transplantation (alloSCT). A high level of minimal residual disease (MRD) before alloSCT has been shown to predict these relapses. Patients at risk might benefit from a preemptive alloimmune intervention. In this first prospective, MRD-guided intervention study, 48 patients were stratified according to pre-SCT MRD level. Eighteen children with MRD level X1 Â 10 À4 were eligible for intervention, consisting of early cyclosporine A tapering followed by consecutive, incremental donor lymphocyte infusions (n ¼ 1-4). The intervention was associated with graft versus host disease Xgrade II in only 23% of patients. Event-free survival in the intervention group was 19%. However, in contrast with the usual early recurrence of leukemia, relapses were delayed up to 3 years after SCT. In addition, several relapses presented at unusual extramedullary sites suggesting that the immune intervention may have altered the pattern of leukemia recurrence. In 8 out of 11 evaluable patients, relapse was preceded by MRD recurrence (median 9 weeks, range 0-30). We conclude that in children with high-risk ALL, immunotherapy-based regimens after SCT are feasible and may need to be further intensified to achieve total eradication of residual leukemic cells.

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“…Hartwig et al [16] showed that repetitive low-dose DLI succeeded in maintaining complete donor chimerism without relapse in a pediatric post-transplant AML patient with mixed chimerism but no evidence of disease, who was followed for 3 years. Their case report supports the concept of combined chemo-immunotherapy for relapsed AML, since the child was re-induced with chemotherapy prior to DLI while the second line treatment consisted of low-dose chemotherapy combined with repetitive lymphocyte infusions.…”

Section: Discussionmentioning

confidence: 99%

“…A 10-year-old boy was diagnosed in September 2004 with monocytic type acute myeloid leukemia (AML, M2) with translocation t(8;21) by PCR. White blood cells (WBC) at presentation were 18.5 3 109 cells/L (normal: 4-10), hemoglobin 7.5 g % (normal: [14][15][16][17][18], and platelets 52 3 109 cells/L (normal: 140-400). After chemotherapy with doxorubicin, etoposide, high-dose cytosine arabinoside (Ara-C) and mitoxantrone (HAM), his bone marrow (BM) showed 30% mast cells, but no evidence of disease.…”

Section: Case Reportmentioning

confidence: 99%

Successful cell‐mediated cytokine‐activated immunotherapy for relapsed acute myeloid leukemia after hematopoietic stem cell transplantation

Gesundheit¹,

Shapira²,

Resnick³

et al. 2008

American J Hematol

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Acute myeloid leukemia (AML) is an extremely aggressive disease with a high relapse rate even after allogeneic hematopoietic stem cell transplantation (HSCT). We report the successful outcome of cell-mediated cytokine-activated immunotherapy in a high-risk pediatric AML patient who relapsed shortly after allogeneic HSCT. Donor lymphocyte infusion along with interferon induced a graft-versus-leukemia effect, presenting as a reversible episode of graft-versus-host disease, which led to stable complete donor chimerism and total eradication of AML for over 24 months, at the time of this report. The curative potential of immunotherapy in hematological malignancies is discussed. Am. J. Hematol. 84:188-190, 2009. V V C 2008 Wiley-Liss, Inc. IntroductionDespite the improved treatment protocols developed in recent years for acute leukemia patients, the survival rate for high-risk pediatric AML patients remains unsatisfactory and the curative options for relapse after allogeneic hematopoietic stem cell transplantation (HSCT) are poor. Immunotherapy has already achieved promising results in the control of various malignancies. Donor lymphocyte infusion (DLI) together with cytokines might constitute a curative approach for relapsed AML patients after allogeneic HSCT, as demonstrated by our patient.

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Maintenance Immunotherapy by Repetitive Low-Dose Donor Lymphocytes Infusions in a Child With Relapse State Aml After Allogeneic Stem Cell Transplantation

Cited by 3 publications

References 9 publications

Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing evidence of mixed chimerism after allogeneic stem cell transplantation

Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing evidence of mixed chimerism after allogeneic stem cell transplantation

Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation

Successful cell‐mediated cytokine‐activated immunotherapy for relapsed acute myeloid leukemia after hematopoietic stem cell transplantation

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