Early allo-SCT for AML with a complex aberrant karyotype—results from a prospective pilot study

Schmid, Christoph; Schleuning, Michael; Tischer, Johanna; Holler, Ernst; Kh, Haude; Braess, Jan; Haferlach, Claudia; Baurmann, Herrad; Oruzio, Daniel; Hahn, J.; Spiekermann, Karsten; Schlimok, Günter; Schwerdtfeger, Rainer; Buechner, Thomas; Hiddemann, Wolfgang; Hj, Kolb

doi:10.1038/bmt.2011.15

Cited by 35 publications

(26 citation statements)

References 23 publications

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“…76 The efficacy of the same approach has been proven in another prospective trial of high-risk AML patients with a complex karyotype. 77 Finally, the use of prophylactic DLI is associated with favorable long-term outcomes. In a recent report of 46 AML patients treated with DLI (pre-emptively due to increasing MC (4), molecular MRDpositive (1), and adjuvant/prophylaxis (41), patients that received DLI had a superior 7-year OS compared with those who did not receive DLI (67 vs 31%).…”

Section: Prevention Of Post-transplant Relapsementioning

confidence: 99%

Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT

Tsirigotis

Byrne

Schmid

et al. 2016

Bone Marrow Transplant

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179

131

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Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a significant proportion of patients with AML will relapse after allo-SCT. The prognosis for these patients is dismal, with a probability of long-term survival of <20%. Data from previous studies have shown that disease-specific prognostic factors, are in general, the same as those in patients treated with conventional chemotherapy. Minimal residual disease (MRD) and chimerism status monitoring after allo-SCT may be used as predictors of impending relapse and should be part of routine follow-up for AML patients. A significant number of studies have shown that pre-emptive administration of donor lymphocyte infusion (DLI) based on MRD and chimerism monitoring, as well as prophylactic DLI in AML patients at high risk of relapse is effective in preventing relapse. In this review, we discuss strategies for the identification of high-risk patients, review current therapeutic options and provide our recommendations for the management of post-SCT AML.

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Section: Prevention Of Post-transplant Relapsementioning

confidence: 99%

Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT

Tsirigotis

Byrne

Schmid

et al. 2016

Bone Marrow Transplant

Self Cite

179

131

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“…Such approaches include timing of transplantation, new combinations of conditioning after preceding chemotherapy, and development of new immunotherapeutic and chemotherapeutic approaches after transplantation. 65,66 In that respect, it is especially encouraging to note that new immunotherapeutic approaches are being developed to be used either pre-or posttransplant.…”

Section: Age and Comorbiditiesmentioning

confidence: 99%

Hematopoietic stem cell transplantation for patients with AML in first complete remission

Cornelissen

Blaise

2016

Blood

268

190

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Postremission therapy in patients with acute myeloid leukemia (AML) may consist of continuing chemotherapy or transplantation using either autologous or allogeneic stem cells. Patients with favorable subtypes of AML generally receive chemotherapeutic consolidation, although recent studies have also suggested favorable outcome after hematopoietic stem cell transplantation (HSCT). Although allogeneic HSCT (alloHSCT) is considered the preferred type of postremission therapy in poor- and very-poor-risk AML, the place of alloHSCT in intermediate-risk AML is being debated, and autologous HSCT is considered a valuable alternative that may be preferred in patients without minimal residual disease after induction chemotherapy. Here, we review postremission transplantation strategies using either autologous or allogeneic stem cells. Recent developments in the field of alternative donors, including cord blood and haploidentical donors, are highlighted, and we discuss reduced-intensity alloHSCT in older AML recipients who represent the predominant category of patients with AML who have a high risk of relapse in first remission.

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“…Two-year survival rates in patients with primary refractory AML ranged between 39 and 69% in studies using this regimen, and a subset of elderly patients (age ⩾ 60) had lower survival of 31%. [44][45][46][47] Comparative studies between this approach and alternative regimens are still lacking.…”

Section: Efficacy-is There An Ideal Conditioning Regimen?mentioning

confidence: 99%

Reduced-intensity conditioned allogeneic SCT in adults with AML

Reshef

Porter

2015

Bone Marrow Transplant

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AML is currently the most common indication for reduced-intensity conditioned (RIC) allo-SCT. Reduced-intensity regimens allow a potent GVL response to occur with minimized treatment-related toxicity in patients of older age or with comorbidities that preclude the use of myeloablative conditioning. Whether RIC SCT is appropriate for younger and more standard risk patients is not well defined and the field is changing rapidly; a prospective randomized trial of myeloablative vs RIC (BMT-CTN 0901) was recently closed when early results indicated better outcomes for myeloablative regimens. However, detailed results are not available, and all patients in that study were eligible for myeloablative conditioning. RIC transplants will likely remain the standard of care as many patients with AML are not eligible for myeloablative conditioning. Recent publication of mature results from retrospective and prospective cohorts provide contemporary efficacy and toxicity data for these attenuated regimens. In addition, recent studies explore the use of alternative donors, introduce regimens that attempt to reduce toxicity without reducing intensity, and identify predictive factors that pave the way to personalized approaches. These studies paint a picture of the future of RIC transplants. Here we review the current status of RIC allogeneic SCT in AML. ( Bone Marrow Transplantation THE RATIONALE FOR RIC IN AMLTraditional myeloablative transplants are effective in part due to a potent immunologic GVL effect independent of the conditioning regimen. The GVL response has been repeatedly demonstrated in allo-SCT 1,2 and through the use of DLI. 3,4 The ability to harness GVL yet minimize toxicity is highly relevant in AML, which is common in older patients and often incurable with chemotherapy alone. In 2013, AML was the most common indication for allo-SCT, 35% of AML transplants were in patients over age 60 and over 40% were performed with reduced-intensity conditioning (RIC) regimens (data from CIBMTR-Center for International Blood and Marrow Transplant Research).Data from animal models 5,6 and clinical observations regarding GVL activity [1][2][3][4]7 facilitated the development of RIC regimens. The success of initial attempts to use low-dose (2 Gy) TBI alone as conditioning was hindered by frequent graft rejections. The addition of fludarabine to low-dose TBI promoted engraftment with encouraging outcomes. [8][9][10][11][12] This supported a conceptual shift in allo-SCT away from dose intensity toward less myelotoxic regimens that rely on a potent GVL response. EFFICACY-IS THERE AN IDEAL CONDITIONING REGIMEN?The definition of RIC has been a moving target. The term 'reduced intensity' describes regimens characterized by lower rates of toxicities compared with myeloablative transplants. RIC regimens can be further classified as non-myeloablative when they result in minimal cytopenias. These regimens presumably have minimal or no direct effect on leukemic cells, relying solely on the GVL response. 13 The CIBMTR defines a RIC regimen ...

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Early allo-SCT for AML with a complex aberrant karyotype—results from a prospective pilot study

Cited by 35 publications

References 23 publications

Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT

Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT

Hematopoietic stem cell transplantation for patients with AML in first complete remission

Reduced-intensity conditioned allogeneic SCT in adults with AML

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