A critical comparison of allogeneic bone marrow transplantation and conventional chemotherapy as treatment for acute nonlymphocytic leukemia.

1984 ◽  
Vol 2 (5) ◽  
pp. 369-378 ◽  
Author(s):  
C B Begg ◽  
P B McGlave ◽  
J M Bennett ◽  
P A Cassileth ◽  
M M Oken
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
Acute Nonlymphocytic Leukemia ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
Critical Comparison ◽  
Selection Factors ◽  
Disease Free

Published data from two centers conducting bone marrow transplantation on patients with acute nonlymphocytic leukemia in first remission were pooled and compared with results from an Eastern Cooperative Oncology Group (ECOG) study in which patients were treated with conventional chemotherapy. A series of adjustments were made to the ECOG sample to account for selection factors that restrict access of patients to transplantation. The transplant sample exhibits considerably higher disease-free survival when compared to the adjusted ECOG series (53% versus 21% at three years). The transplant series is somewhat younger than the ECOG series (median, 24 years versus 28 years). The impact of age on the disease-free survival results is difficult to assess because of the relatively small samples in the different age groups. However, by defining a suitable control group, methodology for making a critical comparison between the two modalities is presented which, if applied to larger samples of patients, should help to resolve the issue. In the absence of data from a large, prospective randomized study, a critical retrospective comparison of available data is essential in the assessment of treatment options.

Allogeneic bone marrow transplantation for patients with acute nonlymphocytic leukemia

Blood ◽  
1984 ◽  
Vol 63 (3) ◽  
pp. 649-656 ◽  
Author(s):  
R Dinsmore ◽  
D Kirkpatrick ◽  
N Flomenberg ◽  
S Gulati ◽  
N Kapoor ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Allogeneic Bone ◽  
Acute Nonlymphocytic Leukemia ◽  
Free Survival ◽  
First Remission ◽  
Disease Free

Abstract Seventy patients with acute nonlymphocytic leukemia (ANLL) underwent allogeneic bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide. Thirty patients underwent transplantation in first remission, 11 in second remission, 3 in third remission, and 26 in relapse. At a median follow-up of 30 mo, 17 of those in first remission and 7 of those in second remission survive in continuous remission, compared to 1 in third remission and 3 in relapse. The 3-yr Kaplan-Meier probability of disease-free survival among the various groups was 55% (+/- 9.2%) for the first remission transplants, 64% (+/- 14.5%) for second remission, 33% (+/- 20%) in third remission, and 10.3% (+/- 6.3%) in the relapse group. Statistical analysis showed a similar survival in the first and second remission groups that was significantly better than that seen in the third remission and relapse groups (p less than 0.01). The improved survival seen in the early remission groups was due to a significant decrease in the incidence of relapse posttransplant (p less than 0.01). These results confirm observations that a significant number of patients transplanted in first remission may achieve extended disease-free survival and document similar results for patients transplanted in second remission.

scholarly journals Allogeneic bone marrow transplantation for patients with acute nonlymphocytic leukemia

Blood ◽  
1984 ◽  
Vol 63 (3) ◽  
pp. 649-656 ◽  
Author(s):  
R Dinsmore ◽  
D Kirkpatrick ◽  
N Flomenberg ◽  
S Gulati ◽  
N Kapoor ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Allogeneic Bone ◽  
Acute Nonlymphocytic Leukemia ◽  
Free Survival ◽  
First Remission ◽  
Disease Free

Seventy patients with acute nonlymphocytic leukemia (ANLL) underwent allogeneic bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide. Thirty patients underwent transplantation in first remission, 11 in second remission, 3 in third remission, and 26 in relapse. At a median follow-up of 30 mo, 17 of those in first remission and 7 of those in second remission survive in continuous remission, compared to 1 in third remission and 3 in relapse. The 3-yr Kaplan-Meier probability of disease-free survival among the various groups was 55% (+/- 9.2%) for the first remission transplants, 64% (+/- 14.5%) for second remission, 33% (+/- 20%) in third remission, and 10.3% (+/- 6.3%) in the relapse group. Statistical analysis showed a similar survival in the first and second remission groups that was significantly better than that seen in the third remission and relapse groups (p less than 0.01). The improved survival seen in the early remission groups was due to a significant decrease in the incidence of relapse posttransplant (p less than 0.01). These results confirm observations that a significant number of patients transplanted in first remission may achieve extended disease-free survival and document similar results for patients transplanted in second remission.

Bone marrow transplantation versus high-dose cytarabine-based consolidation chemotherapy for acute myelogenous leukemia in first remission.

1992 ◽  
Vol 10 (1) ◽  
pp. 41-46 ◽  
Author(s):  
G J Schiller ◽  
S D Nimer ◽  
M C Territo ◽  
W G Ho ◽  
R E Champlin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
High Dose ◽  
Consolidation Chemotherapy ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
First Remission ◽  
Disease Free

PURPOSE Despite substantial progress in the treatment of acute myeloid leukemia (AML), fewer than 25% of patients survive free of leukemia for more than 5 years without allogeneic bone marrow transplantation (BMT). In this study we analyzed the results of one or more cycles of high-dose cytarabine-based consolidation chemotherapy as compared with allogeneic BMT in first remission. PATIENTS AND METHODS The results in 28 adult patients, aged 16 to 45 years, who underwent a closely HLA-matched BMT for AML in first remission were compared with those in 54 consecutive, age-matched, adult patients treated with one or more cycles of high-dose, cytarabine-based consolidation chemotherapy. RESULTS After a median follow-up of 4 years, the actuarial risk of leukemic relapse was considerably lower in the transplant group than in the group treated with consolidation chemotherapy (32% +/- 26% v 60% +/- 14%; P = .05). Treatment-related mortality, however, was much higher in the group treated with BMT (32% v 6%, P = .002). The actuarial disease-free survival at 5 years was not significantly different for the two groups (45% +/- 24% v 38% +/- 14%). CONCLUSIONS Our results show that BMT in first remission AML did not offer a disease-free survival advantage over intensive postremission consolidation chemotherapy. Larger studies are needed to identify patients who might benefit most from BMT.

Taperring Treatment According Minimal Residual Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4960-4960 ◽  
Author(s):  
Ihab A. Eldessouki ◽  
Eman Z Kandeel ◽  
Shady Adnan ◽  
Mohammed Ghareeb ◽  
Ola Gaber ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Salvage Chemotherapy ◽  
Free Survival ◽  
Disease Free ◽  
Minimal Residual

Abstract In spite its established prognostic role in ALL and being a powerful method for patient stratification, Minimal residual disease in AML is still an area of research need to be investigated to decide its value in AML treatment. In this is a retrospective study, 388 adult AML patients from period 2009-2014 in NCI Cairo University were included, comparing minimal residual disease to other prognostic factors to determine its value as an independent prognostic factor to stratify AML patients and to assess possibility of treatment tapering according MRD. We divided patients in to 3 groups according cytogenetics: favorable, intermediate, poor risk. (We considered patients having negative MRD: those having day 28 and day 42 BMA free for MRD less than 0.01) All patients with FLT3 were excluded prior start this study because we proved by other study its grave prognosis and it outweigh MRD as independent prognostic factor, and eventually those patients will relapse within a short period of time. 5 years disease free survival First group patient with favorable cytogenetics: included 156 patients. We found that 76 patients who become MRD negative post first cycle induction had significantly better disease free survival 64% and overall survival 61.7% compared to those having persistence MRD ( 80 patient) post first cycle of induction 24%, 14% respectively with p value 0.02. Out of 76 patients had negative MRD, 29 patients just took 2 cycles of chemotherapy one induction chemotherapy and one consolidation. Those patients continued to maintain CR in spite receiving 2 cycles of chemotherapy which confirm powerful prognostic impact of MRD with DFS : 61, OS 59.3% which showed no significant difference from those who completed their chemotherapy (p value : 0.07) Those patients didn't continue treatment due to medical problems or non compliance or insurance coverage problems. Those who had persistence MRD post first cycle of induction had prognosis resembling those of poor cytogenetics. Out of 80 patients having persistent MRD, 9 died prior relapse due to medical problems. 64 relapsed and took salvage chemotherapy then kept under follow up. 23 patient did allogenic bone marrow transplantation, 9 were in CR and were done due to persistence MRD and 14 patient did due to relapse and transplantation were done in second CR. patients who had did allogenic transplantation had better disease free survival and overall survival. Second group intermediate risk: 103 patients. We had 40 patients with negative MRD, whose DFS and OS were 59% and 55% respectively. Of those patients, 14 received only 2 cycles of chemotherapy and also showed favorable prognosis in spite being intermediate risk and retained CR. DFS : 57%, OS 55% with no statistical difference between those continued chemotherapy or not. 63 Patients had positive MRD, out of them 5 patients had lost follow up. DFS was13% and OS was 11%. 47 patients relapsed took salvage chemotherapy and kept under follow up out of which 16 patients did bone marrow transplantation. 11 patients did bone marrow transplantation due to persistence MRD and they had longer disease free survival compared to those had salvage chemotherapy and kept under follow up. Same disease free survival overall survival to those did BMT post second CR. Third group with poor risk cytogenetic included 127 patients. 32 patients got MRD negative (DFS: 38% OS: 8%). Out of which 9 didn't receive further chemotherapy post 2 cycles. Again with no significant p value between both groups (P: 0.08) We had 95 patients with persistent MRD post induction. 11 patients lost follow up. 65 relapsed and received salvage chemotherapy DFS 29% and OS: 5%. 19 patients did allogenic bone marrow transplantation. 8 patients did allogenic bone marrow transplantation due to persistence MRD. We found that poor risk cytogenetic outweighs MRD and only patients did BMT had favorable outcome regarding disease free survival 42% and overall survival 11%. Finally we conclude that minimal residual disease can be used as independent prognostic factor. Also MRD can be used as in stratifying patients and tailoring the treatment plan allowing the possibility to stop treatment at a less number of cycles and preventing further chemotherapy complications. Disclosures No relevant conflicts of interest to declare.

scholarly journals Bone marrow transplantation in patients aged 45 years and older

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 770-776 ◽  
Author(s):  
HG Klingemann ◽  
R Storb ◽  
A Fefer ◽  
HJ Deeg ◽  
FR Appelbaum ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Survival Rate ◽  
Marrow Transplantation ◽  
Causes Of Death ◽  
Early Stage ◽  
Disease Free Survival ◽  
Advanced Stage ◽  
Free Survival ◽  
Disease Free

Abstract Increasing age has been reported to be a poor prognostic factor for survival after bone marrow transplantation. We evaluated causes of death and frequency and type of complications after marrow grafting in 24 syngeneic and 39 allogeneic recipients who were 45 to 68 years old at the time of transplant. Most patients were in an advanced stage of hematologic malignancy. Among patients given syngeneic transplants, actuarial disease-free survival at 7 years is 20%. The major causes of death were relapse of leukemia and idiopathic interstitial pneumonia. Among allogeneic recipients, 9 (23%) are currently alive, and actuarial disease-free survival at 7 years is 11%. Cytomegalovirus pneumonia and septicemia were the most frequent causes of death. Patients over 50 years of age had the poorest survival rate (1/13), but many of these were transplanted in an advanced stage of their disease. However, among 12 patients transplanted while in remission or at an early stage of their disease, 5 are surviving 65 to 1,160 days after transplantation, with an actuarial survival rate of 22% at 3 years. This is in contrast to those who received their transplant in relapse: 2 out of 20 patients (10%) became long-term survivors, with a probability of survival of 15% at 3 years. The actuarial incidence of grade II through IV acute graft- v-host disease (GVHD) was 30% for allogeneic recipients 45 to 50 years of age. This was not significantly different from the incidence in younger patients. In patients 51 to 62 years of age, the actuarial incidence of acute GVHD was 79%; however, this group included three partially HLA-mismatched transplants. Ten of 15 patients surviving at least 3 months developed chronic GVHD. These results suggest that marrow transplantation is feasible and should be considered in patients over 45 years, especially if recipients are in good clinical condition and are at an early stage of their disease, such as the chronic phase of chronic myelogenous leukemia and preleukemia. For patients more than 50 years of age, allogeneic marrow grafting cannot presently be considered first-line therapy.

scholarly journals Use of recombinant human interleukin-2 in conjunction with syngeneic bone marrow transplantation in mice as a model for control of minimal residual disease in malignant hematologic disorders

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1212-1215 ◽  
Author(s):  
A Ackerstein ◽  
E Kedar ◽  
S Slavin
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Residual Disease ◽  
Interleukin 2 ◽  
Disease Free Survival ◽  
Free Survival ◽  
Hematologic Disorders ◽  
Disease Free ◽  
Minimal Residual

Abstract Unlike allogeneic bone marrow transplantation (BMT), autologous BMT is not accompanied by immune-mediated graft-versus-leukemia (GVL) effects; hence, the relapse rate observed after autologous BMT in malignant hematologic disorders is higher than that observed after allogeneic BMT. Autologous BMT represents a much safer medical procedure available for many patients in need in situations where allogeneic BMT is not feasible or risky. The present experiments were designed to investigate whether it might be possible to combine the therapeutic benefits of autologous BMT with additional immunotherapy after BMT. The tumor model used for investigating GVL effects was the murine B-cell leukemia (BCL1), a spontaneous, nonimmunogenic, highly lethal leukemia of BALB/c origin. BALB/c mice inoculated with 10(3) BCL1 leukemia cells were treated on day-1 with cyclophosphamide 100 mg/kg and transplanted with normal syngeneic BM cells on day 0. High-dose recombinant interleukin-2 (rIL-2) (100,000 Cetus units x 3/day intraperitoneally x 5 consecutive days) was initiated on day +1, +7, or +21 after BMT. Kinetics of lymphocyte reconstitution after syngeneic BMT indicated a steep increase in the absolute number of peripheral blood lymphocytes on days 17 through 24. All experimental groups were observed for relapse. Mice receiving no rIL-2 therapy relapsed and died within 50 days after BMT, whereas mice receiving rIL-2 showed long-term disease-free survival. Optimal time for administration of rIL-2 was noted at 3 weeks post-BMT, with 90% of the mice surviving with no evidence of disease for more than 1 year. Similarly, when 10(4) BCL1 cells were given 1 day after syngeneic BMT to simulate minimal residual disease after syngeneic BMT, rIL-2 therapy administered at 14 days post-BMT seemed effective in prolonging disease-free survival in contrast to the same regimen given at 1 day after BMT. Our data suggest that immunotherapy with rIL-2 should be further investigated as a new immunotherapeutic tool for decreasing the relapse rate after BMT for hematologic malignancies.

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