Long-term leukemia-free survival after allogeneic marrow transplantation in patients with acute myelogenous leukemia

1996 ◽  
Vol 72 (2) ◽  
pp. 53-59 ◽  
Author(s):  
H. T. Greinix ◽  
F. Keil ◽  
S. A. Brugger ◽  
E. Reiter ◽  
W. Linkesch ◽  
...  
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Myelogenous Leukemia ◽  
Free Survival ◽  
Acute Myelogenous ◽  
Allogeneic Marrow Transplantation ◽  
Allogeneic Marrow

scholarly journals Long-term remission from acute myelogenous leukemia after bone marrow transplantation and recovery from acute graft-versus-host reaction and prolonged immunoincompetence

Blood ◽  
1975 ◽  
Vol 45 (2) ◽  
pp. 171-181 ◽  
Author(s):  
WA Bleyer ◽  
RM Blaese ◽  
JS Bujak ◽  
GP Herzig ◽  
RG Jr Graw
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Myelogenous Leukemia ◽  
Graft Versus Host Reaction ◽  
Host Reaction ◽  
Graft Versus Host ◽  
Acute Myelogenous ◽  
Allogeneic Marrow

Abstract A 19-yr-old boy has been in continuous complete remission from acute myelogenous leukemia for 3 yr after allogeneic bone marrow transplantation prepared with combination chemotherapy. During the first year post-transplant, however, the patient developed near-fatal graft-versus-host reaction followed by 11 severe viral and bacterial infections. Immune evaluation during this period revealed multiple defects which were not present prior to transplantation, nor present in the transplant donor: diminution of lymphoid tissue, decline of all immunoglobulin subtypes, deletion of secretory immunoglobulin, disappearance of isohemagglutinins, loss of antibody to diptheria and tetanus toxoids, cessation of cutaneous hypersensitivity to mumps antigen, and inhibition of serum opsonizing activity. The patient was also unable to develop normal humoral or cellular reactivity to brucella antigen, keyhole limpet hemocyanin, or dinitrochlorobenzene. This patient's course illustrates the severity and chronicity of immunoincompetence associated with allogeneic marrow grafting, the importance of early detection and rigorous treatment of infectious disease in these patients, and the need for improved immunologic reconstitution in human marrow transplantation. It also indicates that complete recovery from the immune defects is possible, and that long- term remission from acute myelogenous leukemia can be achieved with allogeneic marrow transplantation.

scholarly journals Long-term remission from acute myelogenous leukemia after bone marrow transplantation and recovery from acute graft-versus-host reaction and prolonged immunoincompetence

Blood ◽  
1975 ◽  
Vol 45 (2) ◽  
pp. 171-181
Author(s):  
WA Bleyer ◽  
RM Blaese ◽  
JS Bujak ◽  
GP Herzig ◽  
RG Jr Graw
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Myelogenous Leukemia ◽  
Graft Versus Host Reaction ◽  
Host Reaction ◽  
Graft Versus Host ◽  
Acute Myelogenous ◽  
Allogeneic Marrow

A 19-yr-old boy has been in continuous complete remission from acute myelogenous leukemia for 3 yr after allogeneic bone marrow transplantation prepared with combination chemotherapy. During the first year post-transplant, however, the patient developed near-fatal graft-versus-host reaction followed by 11 severe viral and bacterial infections. Immune evaluation during this period revealed multiple defects which were not present prior to transplantation, nor present in the transplant donor: diminution of lymphoid tissue, decline of all immunoglobulin subtypes, deletion of secretory immunoglobulin, disappearance of isohemagglutinins, loss of antibody to diptheria and tetanus toxoids, cessation of cutaneous hypersensitivity to mumps antigen, and inhibition of serum opsonizing activity. The patient was also unable to develop normal humoral or cellular reactivity to brucella antigen, keyhole limpet hemocyanin, or dinitrochlorobenzene. This patient's course illustrates the severity and chronicity of immunoincompetence associated with allogeneic marrow grafting, the importance of early detection and rigorous treatment of infectious disease in these patients, and the need for improved immunologic reconstitution in human marrow transplantation. It also indicates that complete recovery from the immune defects is possible, and that long- term remission from acute myelogenous leukemia can be achieved with allogeneic marrow transplantation.

Improved survival for patients with acute myelogenous leukemia.

1995 ◽  
Vol 13 (3) ◽  
pp. 560-569 ◽  
Author(s):  
A J Mitus ◽  
K B Miller ◽  
D P Schenkein ◽  
H F Ryan ◽  
S K Parsons ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
Term Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Acute Myelogenous ◽  
To Receive

PURPOSE Despite improvement in chemotherapy and supportive care over the past two decades, overall survival for patients with acute myelogenous leukemia (AML) remains poor; only 25% to 30% of individuals with this disorder will be cured. In 1987, we initiated a prospective multiinstitution study designed to improve long-term survival in adults with AML. METHODS We modified the usual 7-day treatment scheme of daunorubicin and cytarabine with high-dose cytarabine (HiDAC) on days 8 through 10 (3 + 7 + 3). Allogeneic or autologous bone marrow transplantation (BMT) was offered to all patients who entered complete remission (CR) to decrease the rate of leukemic relapse. Data were analyzed by intention to treat. RESULTS CRs were achieved in 84 of 94 patients (89%; 95% confidence interval [CI], 83 to 95). Because of the high remission rate, factors previously thought to predict outcome, such as cytogenetics, WBC count, French-American-British (FAB) classification, sex, and age, were not useful prognostic variables. The overall survival rate for the entire cohort of patients from data of diagnosis is 55% at 5 years. Sixty percent of all patients who achieved a CR underwent marrow grafting. There was no significant difference in event-free survival (EFS) at 5 years comparing patients assigned to receive allogeneic BMT with patients assigned to receive autologous BMT (56% v 45%, P = .54). CONCLUSION The long-term disease-free survival observed in this study is excellent compared with historical data. This improvement in survival is probably due to the high rate of remission induction, as well as to the effective nature of the consolidation therapy.

Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica Cooperative Group.

1993 ◽  
Vol 11 (6) ◽  
pp. 1046-1054 ◽  
Author(s):  
S Amadori ◽  
A M Testi ◽  
M Aricò ◽  
A Comelli ◽  
M Giuliano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Myelogenous Leukemia ◽  
Marrow Transplantation ◽  
Autologous Bone Marrow Transplantation ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Acute Myelogenous ◽  
First Remission

PURPOSE This study was conducted to assess the comparative values of allogeneic bone marrow transplantation (BMT) and autologous bone marrow transplantation (ABMT) with sequential postremission chemotherapy (SPC) in children with acute myelogenous leukemia (AML) in first remission. PATIENTS AND METHODS From March 1987 to March 1990, 161 assessable patients younger than 15 years of age with newly diagnosed AML were treated uniformly with two courses of daunorubicin and standard-dose cytarabine. After initial consolidation with a course of daunorubicin, cytarabine, and thioguanine (DAT), patients in complete remission (CR) were randomized to receive either ABMT or SPC, except for those with an HLA-matched sibling who were assigned to undergo BMT. SPC consisted of three additional courses of DAT, followed by three pairs of drugs administered sequentially for a total of six cycles. RESULTS Overall, 127 of 161 patients attained CR (79%). The estimated probabilities of survival and event-free survival (EFS) at 5 years for all patients were 42% and 25%, respectively (median follow-up, 28 months). For the 127 complete responders, the 5-year probability of disease-free survival (DFS) was 31%, with a cumulative risk of relapse of 64%. For the purpose of this study, all complete responders were evaluated for analysis of disease outcome according to the intent-to-treat principle, regardless of whether they actually received the intended therapy. The 5-year DFS was 51% for the BMT group (n = 24), significantly higher (P = .03) than that observed for the other cohorts: 21% for ABMT (n = 35), 27% for SPC (n = 37), and 34% for a group of 31 nonrandomized (NR) patients. Bone marrow relapse was the most frequent cause of postremission failure in all therapeutic subgroups, including the BMT cohort, in which no deaths attributable to the toxicity of the procedure were recorded. CONCLUSION The results of this study show that BMT is more effective than ABMT or SPC in preventing leukemia relapse and extending DFS duration in children with AML in first remission.

scholarly journals Phase II Trial of Vorinostat With Idarubicin and Cytarabine for Patients With Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome

2012 ◽  
Vol 30 (18) ◽  
pp. 2204-2210 ◽  
Author(s):  
Guillermo Garcia-Manero ◽  
Francesco Paolo Tambaro ◽  
Nebiyou B. Bekele ◽  
Hui Yang ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Acute Myelogenous Leukemia ◽  
Single Agent ◽  
Complete Response ◽  
Myelogenous Leukemia ◽  
Platelet Recovery ◽  
Free Survival ◽  
Binding Factor ◽  
Deacetylase Inhibitor ◽  
Acute Myelogenous

Purpose To evaluate the safety and efficacy of the combination of the histone deacetylase inhibitor vorinostat with idarubicin and ara-C (cytarabine) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Patients and Methods Patients with previously untreated AML or higher-risk MDS age 15 to 65 years with appropriate organ function and no core-binding factor abnormality were candidates. Induction therapy was vorinostat 500 mg orally three times a day (days 1 to 3), idarubin 12 mg/m2 intravenously (IV) daily × 3 (days 4 to 6), and cytarabine 1.5 g/m2 IV as a continuous infusion daily for 3 or 4 days (days 4 to 7). Patients in remission could be treated with five cycles of consolidation therapy and up to 12 months of maintenance therapy with single-agent vorinostat. The study was designed to stop early if either excess toxicity or low probability of median event-free survival (EFS) of more than 28 weeks was likely. Results After a three-patient run-in phase, 75 patients were treated. Median age was 52 years (range, 19 to 65 years), 29 patients (39%) were cytogenetically normal, and 11 (15%) had FLT-3 internal tandem duplication (ITD). No excess vorinostat-related toxicity was observed. Induction mortality was 4%. EFS was 47 weeks (range, 3 to 134 weeks), and overall survival was 82 weeks (range, 3 to 134 weeks). Overall response rate (ORR) was 85%, including 76% complete response (CR) and 9% in CR with incomplete platelet recovery. ORR was 93% in diploid patients and 100% in FLT-3 ITD patients. Levels of NRF2 and CYBB were associated with longer survival. Conclusion The combination of vorinostat with idarubicin and cytarabine is safe and active in AML.

scholarly journals Detection and Characterization of Primitive Malignant and Normal Progenitors in Patients With Acute Myelogenous Leukemia Using Long-Term Coculture With Supportive Feeder Layers and Cytokines

Blood ◽  
1997 ◽  
Vol 90 (7) ◽  
pp. 2555-2564 ◽  
Author(s):  
Laurie E. Ailles ◽  
Brigitte Gerhard ◽  
Donna E. Hogge
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Culture Conditions ◽  
Mouse Fibroblast ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Information Culture ◽  
Normal Individuals ◽  
Exogenous Addition ◽  
Acute Myelogenous

Abstract Analysis of the mitogenic activity of interleukin-3 (IL-3), Steel factor (SF ), and flt-3 ligand (FL) on acute myelogenous leukemia (AML) blasts using the short-term endpoints of proliferation in 3H-thymidine (3H-Tdr) incorporation assays or methylcellulose cultures (colony assays) showed that greater than 90% of samples contained cells that were responsive to one or more of these cytokines. With this information, culture conditions that were known to support normal long-term culture-initiating cells (LTC-IC) were tested, with or without supplements of one or more of these three growth factors, for their ability to support primitive progenitors from 10 cell samples from patients with AML. In all cases cytogenetically abnormal colony forming cells (CFC) were detected after 5 weeks when AML peripheral blood or marrow cells were cocultured on preestablished, normal human marrow feeders (HMF ) and/or Sl/Sl mouse fibroblast feeders and the number of CFC detected in these 5-week-old LTC maintained a linear relationship to the number of input AML cells. Limiting dilution analysis, performed on 6 of the 10 samples, showed the frequency of AML cells initiating LTC (AML LTC-IC) to be 5- to 300-fold lower than the frequency of AML-CFC in the same cell sample, whereas the average number of CFC produced per LTC-IC varied from 1 to 13. Surprisingly, in each case the concentration of cytogenetically normal LTC-IC detected in AML patient blood was at least 10-fold higher than that previously observed in the blood of normal individuals. “Mixed” mouse fibroblast feeders engineered to produce human G-CSF, IL-3, and SF did not enhance detection of AML LTC-IC but did increase the output of cytogenetically normal CFC from LTC of 3 of 4 patient samples. Supplementation of AML LTC with IL-3 and exogenously provided SF and/or FL increased the output of AML-CFC from 5-week-old LTC by greater than or equal to twofold with 5 of 9 patient samples, whereas in one case exogenous addition of FL reduced the output of malignant CFC from LTC. These studies show that conditions that support normal LTC-IC also allow a functionally analogous but rare AML progenitor cell type to be detected. In addition, differences in the responses of normal and leukemic cells to various cytokines active on normal LTC-IC were revealed. Further analysis of these differences may enhance our understanding of leukemogenesis and lead to observations that could be exploited therapeutically.

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