Extramedullary relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcomes

Abstract

Articleshaematologica | 2013; 98 (2) 179 IntroductionAllogeneic hematopoietic stem cell transplantation (HSCT) is increasingly used as a potentially curative treatment for acute myeloid leukemia (AML).1 However post-HSCT relapse remains an important cause of treatment failure with relapse rates ranging from 30% to 70%, 2-5 depending on a number of factors such as disease status at the time of transplantation, donor source, conditioning regimen, and T-cell content of the graft. 4,6 Extramedullary relapses are known to occur post-HSCT, either as isolated sites of relapse or in combination with marrow relapse, 7-9 and usually result in death. 10,11 Although risk factors for extramedullary disease/relapse have been described in newly diagnosed leukemia patients, 12 there have been few studies supporting the extrapolation of these factors to the post-HSCT setting. Despite the potential importance of post-HSCT extramedullary relapse as a determinant of outcomes, the incidence, risk factors, and treatment of this condition are not well understood, especially in light of the many changes in HSCT strategies over the past 20 years.Given the need for a better understanding of post-HSCT extramedullary relapse, we performed a retrospective analysis of patients who underwent HSCT for AML at the Design and MethodsDisease-, transplant-and outcome-related data were collected using protocols approved by the Institutional Review Board. Patients were treated according to clinical protocols approved by our Institutional Review Board and/or institutional care practice guidelines.Information on the patients and their transplants are shown in Table 1. Patients were classified as having high risk cytogenetics if they had any of the following: 5q-, monosomy 7/7q-, complex cytogenetics or FLT-3 positivity. Myeloablative conditioning regimens included busulfan (12.8 mg/kg IV or oral equivalent) combined with cyclophosphamide (120-200 mg/kg) ± cytarabine (6 g/m 2 ), fludarabine (140 mg/m 2 ), or clofarabine (150 mg/m 2 ), or total body irradiation (1200 cGy) combined with cyclophosphamide (120 mg/kg). Reduced intensity regimens included fludarabine (140 mg/m 2 ) and either busulfan (6.4 mg/kg IV or oral equivalent) or melphalan (140 mg/m 2 ). Immunosuppression primarily consisted of a calcineurin inhibitor (tacrolimus or cyclosporine) with methotrexate (5 mg/m 2 on days 1, 3, 6, and 11; n=211) or mycophenolate (20-30 mg/kg/day, maximum 3000 mg/day on days 0-28; n=46). Patients enrolled in graft-versus-host (GVHD) prevention clinical trials (n=29) received sirolimus in lieu of methotrexate, or etanercept as additional pro- Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2012.073189 Manuscript received on June 29, 2012.Manuscript accepted on September 12, 2012 Extramedullary relapse after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia is a contributor to post-transplant mortality but risk factors for, and outcomes of, this condition are not well characterized. We analyzed 257 cons...

Cytomegalovirus Infection in Patients Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation in Portugal: A Five-Year Retrospective Review

“…In fact, disease relapse is a relatively frequent event, ranging from 30% to 70%, and is dependent on the several factors including disease status at the time of transplantation, donor source and conditioning regimen (50)(51)(52). Recently, a study from Elmaagacli et al has shown that CMV reactivation was associated with reduced risk of relapse in patients with acute myeloid leukemia (53) and actually, these results were corroborated by a few authors that describe similar evidences (26,42,54).…”

Molecular and cellular aspects of extramedullary manifestations of acute myeloid leukemia

“…Furthermore, HSCT not only is not an effective procedure for EML, but it can also increase the risk of EML relapse in AML patients. [71] Studies reviewed in this article suggest that cases of AML that have blasts with relatively specific characteristics have a highrisk for non-hematopoietic tissue infiltration. These features may be very helpful in distinguishing patients susceptible to EMI.…”

Feasibility of Treating Post-Transplantation Minimal Residual Disease in Children with Acute Leukemia

“…This strategy, however, may not be useful for predicting extramedullary relapse, which may not be reliably detected with bone marrow monitoring. (21, 26, 30) Six patients in our study presented with extramedullary relapse as the first manifestation of disease recurrence without prior marrow disease involvement.…”