Impact of disease burden at time of allogeneic stem cell transplantation in adults with acute myeloid leukemia and myelodysplastic syndromes

Abstract

Summary:The impact of disease burden on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (SCT) has not been well defined. Data from several retrospective series suggest that overt leukemia at the time of transplant increases the risk of relapse. We reviewed the outcomes of 68 consecutive adults with AML (n ¼ 60) or myelodysplastic syndromes (MDS) (n ¼ 8) who received an allogeneic SCT at the University of Chicago between May 1986 and October 2002 to confirm the importance of currently recognized risk factors for overall survival (OS) and progression-free survival (PFS). In addition, we wanted to determine whether quantification of residual disease by blast percentage or cytogenetic abnormalities at the time of SCT was correlated with outcome. AML subtypes based on the FAB classification were as follows:Cytogenetic analysis was available from 52 patients. Using standard morphologic criteria, 34 patients were in complete remission (CR) and 34 had visible leukemia present. The majority of donors were HLA-identical siblings (n ¼ 55). In all, 56 patients received myeloablative conditioning regimens and 12 received a reduced-intensity, fludarabine-based conditioning regimen. OS and PFS times were 7.1 months (95% CI, 4.8-10.4) and 5.1 months (95% CI, 3.2-7.8), respectively. Median follow-up from SCT was 4.6 years (range, 0.6-17.0) for survivors. In multivariate analysis, the following factors were found to be associated with worse survival: (1) increased percentage of blasts in the bone marrow at the time of SCT, (2) presence of acute graft-versus-host disease, (3) mismatched donor, (4) Zubrod performance score of X2, and (5) age X45 years. We also found a trend towards improved outcome among patients in cytogenetic remission as compared to those who had residual cytogenetic abnormalities and those in overt relapse. These data support an association between pre-transplant disease burden and poor outcome after SCT.Bone Marrow Transplantation (2005) 35, 965-970.

Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML

“…However, if leukemic blasts is present-even in small numbers-their presence in the BM (tumor burden) is associated with poorer outcome, irrespective of morphologic blast count. 14,15,42 This is particularly applicable for RIC allo-HCT. 11,21,[43][44][45] We observed a reduced risk of relapse in CMV seropositive recipients.…”

“…9 It is clear that patients with active leukemia had more relapse and worse OS after allo-HCT regardless of donor type or patient age. [10][11][12][13][14][15] Following allo-HCT, 40-60% of AML patients in CR1 enjoy long-term OS, whereas o20% of refractory or relapsed AML patients survive. 1,11 Yet even for allo-HCT during CR, relapse remains the most frequent complication of allo-HCT.…”

Impact of pretransplant comorbidities on alemtuzumab-based reduced-intensity conditioning allogeneic hematopoietic SCT for patients with high-risk myelodysplastic syndrome and AML

“…12,32,[39][40][41] The presence of active disease at the time of transplantation remained the strongest predictor of inferior transplant outcome, indicating that this cohort of patients should be considered for alternative therapeutic strategies. The role of dose-escalated conditioning regimens or sequential chemotherapy followed by RIC HSCT has been investigated by other groups in this context, with promising results.…”

“…[7][8][9][10][11][12][13][14][15][16] Recent literature has indicated that performance status of transplant recipients, rather than recipient age per se, may be a better indicator of the ability of a patient to tolerate allo-HSCT. The Charlson comorbidity index, adapted for HSCT, has been shown to predict NRM in patients receiving allogeneic HSCT.…”

Prognostic and therapeutic implications of minimal residual disease at the time of transplantation in acute leukemia

“…50,51 In contrast, the prognostic role of pre-HCT MRD in non-APL AML is primarily studied via MFC-based assays to detect and quantify MRD. 46,47,[52][53][54][55][56][57][58][59][60][61] Nevertheless, as summarized in Table 4, more recent series show that both pediatric and adult patients with non-APL AML who are MRD À by current sensitive methods have excellent outcomes following myeloablative AlloHCT, with 2-5 year OS estimates around 75-80%. 47,58,61 For such patients, even AutoHCT may result in good disease control, with some studies showing 5-year OS estimates in the 60-70% range.…”