AML In Second Remission Research Articles

Allo-SCT using BU, CY and melphalan for children with AML in second CR

Based on the results from the AML-BFM 98 trial, hematopoietic SCT (HSCT) is recommended for children with AML in second CR only. Here, we retrospectively analyze interphase data of children who underwent HSCT after myeloablative conditioning with BU, CY, and melphalan (BuCyMel) for AML in second remission (CR2) between 1998 and 2009. Out of 152 children, transplant data were available on 109 individuals. Sixty out of 109 children (55%) received BuCyMel. Median age at HSCT was 12.2 years (range 3.0; 18.3). GVHD prophylaxis mostly consisted of CsA and short term MTX with or without antithymocyte globulin. Matched-sibling donors were used for 6/60 analyzed recipients, the remainder either received grafts from matched unrelated (30/60) or mismatched donors. OS after 5 years was 62% (s.e. 6%), relapse incidence 35% (18/60 children) and treatment-related mortality accounted for 12% (7/60) of fatal events. In conclusion, even taking into account possible selection bias in this retrospective analysis, HSCT in CR2 using BuCyMel resulted in a respectable OS. Based on this data the prospective, controlled and centrally monitored AML SCT-BFM 2007 trial has started to recruit patients in January 2010 aiming to generate valid outcome data for further strategy decisions.

Auto-SCT for AML in second remission: CALGB Study 9620

We studied the feasibility and efficacy of a two-step approach to Auto-SCT for patients with AML in second remission. Step 1 consisted of consolidation chemotherapy using cytarabine 2000 mg/m(2) i.v. every 12 h for 4 days plus etoposide 40 mg/kg total dose by continuous i.v. infusion over the same 4 days. PBSC were collected after G-CSF stimulation during recovery from this chemotherapy. Step 2, auto-SCT, used a preparative regimen of oral BU 16 mg/kg over 4 days followed by etoposide 60 mg/kg i.v. Of the 50 patients entered on Step 1, two died from treatment complications, and seven failed to proceed to transplantation. A median CD34+ cell dose of 5.9 x 10(6)/kg was collected in a median of three collections. With a median follow-up of 8.2 years, 5-year disease-free survival (DFS) is 28%. The most important prognostic factor was cytogenetics, with acute promyelocytic leukemia (APL) patients having a 5-year DFS of 67% compared with 16% for others. We conclude that this two-step approach to autologous transplantation produces good CD34+ mobilization and that this approach has cured some patients. Results in patients with APL are especially promising.

Outpatient total body irradiation for pediatric patients undergoing stem cell transplantation.

We have retrospectively reviewed the ability to safely deliver total body irradiation (TBI) in the outpatient setting in 10 pediatric patients undergoing stem cell transplantation. Patients had a median age of 14 years (range 9-17 years) with diagnoses that included ALL in second remission, AML in second remission, myelodysplastic syndrome, Ewing's sarcoma, and rhabdomyosarcoma. Patients received a total of 1375 cGy or 1440 cGy given in a hyperfractionated schedule (11 or 12 fractions) over a 4-day period. All children were seen in the outpatient clinic daily during TBI and all were housed within a 20 mile radius of our institution during this period. Eight patients achieved good control of nausea and emesis with ondansetron alone while two patients required ondansetron and diphenhydramine. Nine patients received some form of intravenous hydration during this period (hyperalimentation, fluid boluses in clinic, or night-time intravenous fluids). One patient maintained good hydration with oral intake alone. Only one child required admission during this period for persistent nausea and vomiting despite antiemetics and intravenous fluids. A cost approximation suggests that TBI delivered in the outpatient setting resulted in a saving of approximately $2400 per patient. We conclude that TBI administered to children and adolescents in the outpatient setting can be a safe and cost-effective practice.

Autologous Bone Marrow Transplantation in the Treatment of Acute Myeloid Leukemia: The Dartmouth Experience and a Review of Literature

Autologous bone marrow transplantation is increasingly being investigated as a treatment for patients with acute myelogenous leukemia. Review of the literature demonstrates that much of the data are incomplete. Most reports contain small numbers of patients, making analysis of any particular regimen difficult to assess. The morbidity and mortality of the procedure appear to be substantially less than that seen in the allogeneic setting. The major complications relate to problems with engraftment. Recovery of platelet production to normal levels is frequently cited as delayed, and in some patients, does not occur. This phenomenon may be heightened by marrow manipulation during purging or posttransplant drug therapy. It is not known if this is a problem related to stem cells or related to the changes in the hematopoietic microenvironment. The results of autologous bone marrow transplantation for patients with acute myeloid leukemia suggest that, as with standard chemotherapy, there is little survival benefit when patients are in relapse at the time of transplantation. There are few long-term survivors, and relapse within 5 months is the rule. It should be noted that the vast majority of the studies reported here have used marrow that has not been treated in an attempt to remove occult leukemia cells. The use of purged bone marrow has not yet been adequately studied. In patients in second or subsequent remission, ABMT appears to offer a chance for long-term survival not seen with present second-line standard chemotherapy regimens and should be considered a viable option for patients under the age of 55. The results to date do not define whether marrow purging is beneficial, and most studies being carried out at the present time are not evaluating this question. The majority of studies are examining different methods of purging. The result of our study in patients in second and third remission using in vitro purging of bone marrow with monoclonal antibodies PM-81 and AML2-23 are encouraging, as are the studies of purging with 4-HC. The Cancer and Leukemia Group B has just begun a study for patients with AML in second remission using the protocol we piloted at Dartmouth. We are also evaluating the feasibility of using this therapy in patients at the time of first relapse, as studies in the allogeneic setting have suggested the results are similar to those achieved in second remission (60).(ABSTRACT TRUNCATED AT 400 WORDS)