Allogeneic Bone Marrow Transplantation for Therapy-Related Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Long-Term Study of 70 Patients—Report of the French Society of Bone Marrow Transplantation

To control disease before allogeneic hematopoietic cell transplantation (HCT) for relapsed/refractory AML, we used clofarabine cytoreduction. Seventeen patients received clofarabine 30-40 mg/m 2 i.v. daily for 5 days with plans to initiate conditioning during the nadir, 14 days later. Bone marrow biopsy 12 days after clofarabine showed effective cytoreduction (that is,o20% cellularity with o10% blasts) in 10 of 17 patients (59%). Ineffective cytoreduction correlated with lower PFS (3.8 vs 6.4 months; HR ¼ 2.7, 95% CI ¼ 1.10-14.29, P ¼ 0.035) and OS (5.1 vs 16.6 months; HR ¼ 2.5, 95% CI ¼ 0.98-12.17, P ¼ 0.053). Significant toxicities before HCT, attributable to clofarabine, were grade 1-2 hyperbilirubinemia (18%); grade 1-2 (59%) or grade 3-4 (18%) transaminitis; and grade 1-2 (18%) creatinine elevation. Sixteen patients proceeded to HCT infusion 22 days (median) after initiation of clofarabine. Day 100 and 2-year transplant-related mortality were 6 and 36%. Nine patients relapsed. One year PFS and OS were 25 and 38%, respectively. Two patients are alive in remission at 18 and 52 months. Clofarabine cytoreduction followed by immediate HCT is feasible with acceptable toxicity and TRM. Outcomes for this cohort of patients with refractory AML remain poor and we are studying this approach in a prospective manner.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Feasibility of clofarabine cytoreduction before allogeneic transplant conditioning for refractory AML

Locke

Artz

Rich

et al. 2010

“…6,7,[13][14][15][16] Here we present a retrospective long-term followup analysis of 79 unselected consecutive t-MDS/t-AML patients who underwent aHCT after predominantly RIC (73.4%) between 1995 and 2014. With a median follow-up of 7.5 years, this is one of the longest reported follow-up studies for this specific patient clientele, revealing a 10 year OS and DFS rate of 24% (13-36%) and 24% (14-36%), respectively, whereas the NRM rate was 32% (22-46%).…”

Section: Discussionmentioning

confidence: 99%

Long-term follow-up of therapy-related myelodysplasia and AML patients treated with allogeneic hematopoietic cell transplantation

Finke

Schmoor

Bertz

et al. 2016

The outcome of patients with therapy-related myelodysplasia (t-MDS) or t-AML is very poor. The only curative treatment option implements allogeneic hematopoietic cell transplantation (aHCT); however, long-term follow-up data beyond 5 years are scarce. Here we report on a cohort of 79 consecutive patients with a median age of 58 years (range (r): 20-76) at transplantation and a median follow-up of 7.5 years (r: 0.07-19.0). Only 19 (24.1%) patients were in CR before aHCT. Non-relapse mortality and relapse rates were 23% (95% confidence interval, 15-35%) and 42% (32-55%) at 5 years, and 32% (22-46%) and 44% (34-57%) at 10 years, respectively. Disease-free survival (DFS) and overall survival (OS) rates were 35% (24-46%) and 38% (27-49%) at 5 years, and 24% (14-36%) and 24% (13-36%) at 10 years, respectively. Although cytogenetic aberrations were associated with shorter DFS and higher relapse risk, persistent disease at the time of transplantation, an unrelated donor and patient age were not associated with shorter OS. In conclusion, long-term survival beyond 10 years of t-MDS/t-AML patients after aHCT is possible, even for refractory patients. Therefore, early donor search and rapid transplantation are warranted, also to decrease the risk of disease-related deterioration of patients' performance status.Bone Marrow Transplantation (2016) 51, 771-777; doi:10.1038/bmt.2015.338; published online 11 January 2016 INTRODUCTION Cytotoxic agents, especially alkylating and topoisomerase II targeting drugs, as well as ionizing radiotherapy in the successful treatment of most cancer types and to some extent also in nonmalignant diseases, bear a significant long-term risk of developing therapy-related malignancies such as myelodysplasia (t-MDS) and t-AML. 1,2 Despite intensive efforts to reduce the risk of developing t-MDS/t-AML by using fewer cycles of dose-intense chemotherapy for a given primary disease and thus to decrease cumulative doses, this late occurring side effect remains a challenging clinical problem. 3 Treatment of t-MDS/t-AML, which often occurs with other comorbidities, is complex and the outcome of patients treated with low-or even high-dose chemotherapy alone remains poor. Beyond other factors, this is especially attributed to older age, therapy resistance and cytogenetic abnormalities including monosomies or complex karyotypes. 4,5 In recent years, it has become evident that the most successful curative treatment concept for t-MDS/t-AML patients resulting in substantial remission rates implements allogeneic hematopoietic cell transplantation (aHCT). Using a myeloablative conditioning regimen in 77% of patients in a cohort of 868 patients with a median age of 40 years, Litzow et al. 6 reported an overall survival (OS) rate of 22% (95% confidence interval (CI), 19-26%) after 5 years, although the non-relapse mortality (NRM) and relapse rate at that time were 48% (95% CI, 44-51%) and 31% (95% CI, 28-34%), respectively. In another study from the European Group for Blood and Marrow Transplantation, Kröger et al. 7...

“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

Lim

Ingram

Brand

et al. 2009

We report a retrospective analysis of 128 consecutive patients with high-risk myelodysplastic syndrome (MDS) and AML who received an alemtuzumab-based reducedintensity conditioning hematopoietic SCT (RIC HSCT). The median recipient age was 53 years (range 21-72 years). A total of 49 (38%) recipients had a sibling donor and 79 (62%) had a volunteer-unrelated donor. The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was assigned to all patients with a score of 0 in 40 (31%), of 1-2 in 45 (35%) and X3 in 43 (34%) patients. The 3-year non-relapse mortality (NRM) was 31%, disease-free survival (DFS) was 41% and overall survival (OS) was 46%. The 3-year NRM for patients with a HCT-CI score of 0, 1-2 or X3 was 16, 24 and 42%, respectively. The 3-year DFS and OS by HCT-CI was 58 and 69% (score 0), 39 and 39% (score 1-2) and 24 and 32% (score X3), respectively. On multivariate analysis, HCT-CI was an independent variable affecting 3-year NRM, DFS and OS (P-value ¼ 0.04, 0.01 and o0.01, respectively). Although the disease stage at the time of transplant was an additional independent predictive variable on transplant outcomes, recipient age (4/o50 years) did not have a significant predictive impact. In MDS or AML patients with advanced disease receiving alemtuzumab-based RIC HSCT, the HCT-CI provides an important means of stratifying patients with a high risk of inferior transplant outcomes.