A Prospective Multicenter Trial of Peripheral Blood Stem Cell Sibling Allografts for Acute Myeloid Leukemia in First Complete Remission Using Fludarabine-Cyclophosphamide Reduced Intensity Conditioning

A total of 50 consecutive patients (median age, 57.5 years) with AML (n ¼ 30) or myelodysplasia (MDS, n ¼ 20) underwent HLA matched related donor (MRD, n ¼ 27) or unrelated donor (MUD, n ¼ 23) peripheral blood hematopoietic cell transplantation after nonmyeloablative CY/fludarabine (Flu) conditioning. GVHD prophylaxis included CsA (n ¼ 19) ± mycophenolate mofetil (n ¼ 31). At a median follow-up of 59 months, 21 patients (42%) were alive without evidence of disease. By Kaplan-Meier analysis, year 1-4 disease-free survival (DFS) and OS estimates were 0.50/0.58, 0.40/0.46, 0.37/0.43 and 0.37/0.41. MUD recipients were engrafted quickly (13.5 days) compared to MRD recipients (16 days) and relapsed/progressed less frequently (P ¼ 0.005). Overall grade 3/4 acute GVHD (aGVHD) occurred in 26% in the absence of antecedent mucositis and was associated with chronic GVHD (cGVHD) and poor OS. Extensive cGVHD developed in 51.2% of 100 day survivors. Rates of aGVHD, cGVHD and survival were similar between MRD and MUD recipients. Of 14 survivors with cGVHD, 5 (35.7%) experienced resolution off immunosuppression, suggesting that tolerance with HLA matched grafts is possible at an advanced age by this method. This study provides further evidence for prolonged DFS after CY/Flu MRD allotransplantation for AML/MDS, and extends the findings to older patients and those with unrelated donors.

Section: Discussionsupporting

confidence: 59%

“…Grigg et al 42 recently reported results of a clinical investigation using nonmyeloablative CY/Flu to prepare 34 patients with de novo AML in first CR for matchedsibling allotransplantation. Patients experienced relatively low incidences of grades 2-4 aGVHD (21%) and cGVHD (24%).…”

Section: Discussionmentioning

confidence: 99%

Long-term disease-free survival after nonmyeloablative cyclophosphamide/fludarabine conditioning and related/unrelated allotransplantation for acute myeloid leukemia/myelodysplasia

Nelson

Schwartz

et al. 2010

“…31 Data from a prospective study with a RIC regimen resulted in a 2-year relapse incidence of 37% following fludarabine and CY conditioning in patients with AML in CR1. 41 With an OS and DFS of 61 and 55% at 2 years, the survival data following treosulfan and fludarabine conditioning in AML patients are in the upper range of those previously reported. Pidala et al, (2011) 38 reported a similar 2-year OS rate of 62% for patients in CR1 following targeted standard dose IV BU/fludarabine conditioning.…”

Section: Discussionmentioning

confidence: 75%

“…43 Similar results for overall and disease free survival compared with the present study were obtained after RIC with fludarabine and CY (68% and 56%, respectively). 41 However, those study patients probably had more favorable disease-specific prognostic profiles and transplant characteristics; 85% of the patients had an intermediate cytogenetic risk, and all patients were in CR1 and received PBSCs from a sibling donor.…”

Section: Discussionmentioning

confidence: 94%

Allogeneic hematopoietic SCT in patients with AML following treosulfan/fludarabine conditioning

Casper

Hołowiecki

Trenschel

et al. 2011

An alternative reduced-toxicity conditioning regimen for allogeneic transplantation, based on treosulfan and fludarabine, has recently been identified. The safety and efficacy of this new conditioning regimen has been investigated prospectively in patients with AML. A total number of 75 patients with AML in CR were treated with 3 Â 14 g/m 2 treosulfan and 5 Â 30 mg/m 2 fludarabine, followed by matched sibling or unrelated SCT. Patients were evaluated for engraftment, adverse events, GVHD, and for nonrelapse mortality, relapse incidence, overall and disease-free survival (DFS). All patients showed primary engraftment of neutrophils after a median of 20 days. Non-hematological adverse events grade III --IV in severity included mainly infections (59%) and gastrointestinal symptoms (7%). Acute GVHD grade II --IV occurred in 21% and extensive chronic GVHD occurred in 16% of the patients. After a median follow-up of 715 days, the 2-year overall and DFS estimates were 61% and 55%, respectively. The 2-year incidences of relapse and non-relapse mortality reached 34% and 11%, respectively. In summary, our data confirm promising safety and efficacy of the treosulfan-based conditioning therapy in AML patients, ClinicalTrials.gov Identifier: NCT01063660.

“…73,74 Reduced-intensity allogeneic transplants in AML The ability of reduced-intensity allografts to deliver durable remissions in older patients with high-risk AML has now been demonstrated by a number of groups. 7,9,10,[75][76][77][78][79][80][81] Although longer-term follow-up is still required on these cohorts it is likely that RIC allografts represent a major advance in the treatment of AML in older patients and important questions concerning the optimal reducedintensity regimen and the integration of RIC allografts into the overall management of older patients must now be addressed.…”

Section: The Role Of Allogeneic Transplantation In Management Of Patimentioning

confidence: 99%

Full-intensity and reduced-intensity allogeneic stem cell transplantation in AML

Craddock

2008

Allogeneic stem cell transplantation represents the most active form of anti-leukaemic therapy in acute myeloid leukaemia (AML). Advances in transplant technology and supportive care have resulted in improved outcomes in patients allografted using a myeloablative conditioning regimen. At the same time the use of reduced-intensity conditioning regimens has allowed an immunologically mediated graft-versus-leukaemia effect to be exploited in older patients who were previously ineligible for transplantation on the grounds of age or comorbidity. This coupled with the increased availability of alternative stem cell sources, in the form of either unrelated or cord blood donations, has established allogeneic transplantation as a key therapeutic strategy in the treatment of both younger and older adults with AML.