Unrelated Transplantation for Poor-Prognosis Adult Acute Lymphoblastic Leukemia: Long-Term Outcome Analysis and Study of the Impact of Hematopoietic Graft Source

Abstract

Adults with high-risk acute lymphoblastic leukemia (HR-ALL) have a poor outcome with standard chemotherapy and usually undergo unrelated stem cell transplantation (SCT) if a matched sibling donor is not available. We analyzed the outcome of adult patients with unrelated SCT for HR-ALL and studied the possible effect of the hematopoietic stem cell source of the transplant. A total of 149 adult patients (median age, 29 years, range, 15-59 years) with HR-ALL underwent unrelated SCT in 13 Spanish institutions between 2000 and 2007. Patients in first complete remission (CR1) at transplantation had at least one adverse prognostic factor (advanced age, adverse cytogenetics, hyperleukocytosis, or slow response to induction therapy). ALL was in CR1 in 81 patients (54%), in second CR (CR2) in 37 patients (25%), in third CR (CR3) in 11 patients (7%), and with overt disease in 20 patients (13%). The hematopoietic source was unrelated cord blood (UCB) in 62 patients and an unrelated donor (UD) in 87 patients. The patients undergoing UCB-SCT and UD-SCT were comparable in terms of the main clinical and biological features of ALL, except for a higher frequency of patients with more overt disease in the UCB-SCT group. There was no statistically significant difference in overall survival (OS) or disease-free survival (DFS) at 5 years between the 2 groups. Treatment-related mortality (TRM) was significantly lower in the UCB-SCT group (P = .021). The probability of relapse at 1 year was 17% (95% confidence interval [CI], 7%-27%) for the UD-SCT group and 27% (95% CI, 14%-40%) for the UCB-SCT group (P = .088), respectively. Only disease status at transplantation (CR1, 41% [95% CI, 18%-64%] vs CR2, 51% [95% CI, 17%-85%] vs advanced disease, 66% [95% CI, 46%-86%]; P = .001) and the absence of chronic graft-versus-host disease (74% [95% CI, 46%-100%] vs 33% [95% CI, 17%-49%]; P = .034) were significant factors for relapse. All unrelated transplantation modalities were associated with high treatment-related mortality for adult HR-ALL patients without a sibling donor. UCB-SCT and UD-SCT were found to be equivalent options. Disease status at transplantation and chronic GVHD were the main factors influencing relapse in both transplantation modalities.

Risk factors for outcomes after unrelated cord blood transplantation for adults with acute lymphoblastic leukemia: a report on behalf of Eurocord and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

“…The Spanish group has reported outcomes of 62 high-risk ALL patients receiving UCBT compared with 87 transplanted with matched unrelated donor grafts, with no significant differences in RI, LFS or OS. 12 Data on outcomes after UCBT for ALL adult patients are scarce. [13][14][15] One Japanese series reported in 2009 outcomes of Abbreviations: cGVHD = chronic GVHD; LFS = leukemia-free survival; RIC = reduced intensity conditioning; UCBT = unrelated cord blood transplantation.…”

“…Different comparative studies on stem cell sources reported similar outcomes after unrelated donor allo-HSCT or unrelated CB transplantation (UCBT) for adults with acute leukemias. [8][9][10][11][12] To date, only a few studies have critically assessed the overall outcomes after UCBT for adult ALL. [13][14][15] To describe outcomes and risk factors after UCBT for adult ALL, with the aim to evaluate whether it is a suitable option to treat this population, we designed a retrospective registry-based analysis including 421 patients who received UCBT in European group for blood and marrow transplantation (EBMT) centers.…”

Quantification of minimal residual disease levels by flow cytometry at time of transplant predicts outcome after myeloablative allogeneic transplantation in ALL

“…1 Results using alternative stem cell sources or alternative donors have improved in the last decade, and current outcomes after HSCT are strongly correlated with clinical disease status. [2][3][4][5] The optimal results in both children and adults are obtained when patients underwent HSCT at early stages of the disease as measured by conventional morphological remission. [5][6][7] Over the last decade, the concept of remission in ALL has evolved owing to use of molecular techniques and multiparameter flow cytometry (MFC) to more precisely track residual leukemic cells during chemotherapy treatment.…”

The role of HLA-matched unrelated transplantation in adult patients with Ph chromosome-negative ALL in first remission. A decision analysis

“…Several studies have suggested that unrelated HSCT may be effective for high-risk adult ALL patients in various disease statuses. 31,32 In addition, two retrospective studies showed no difference between related and unrelated HSCT for adult ALL patients, including those in CR1, 12,13 and the recent evidencebased review from the American Society for Blood and Marrow Transplantation supported this. 33,34 However, patients who undergo unrelated HSCT in CR1 are a select population of patients who have maintained their remission status during the donor-coordination process.…”