Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia.

1991 ◽  
Vol 9 (9) ◽  
pp. 1570-1574 ◽  
Author(s):  
S J Forman ◽  
G M Schmidt ◽  
A P Nademanee ◽  
M D Amylon ◽  
N J Chao ◽  
...  

The survival of patients with acute leukemia who do not achieve a remission with primary therapy is very poor. High-dose chemoradiotherapy followed by allogeneic bone marrow transplantation (BMT) has been shown to be effective therapy for patients with acute and chronic leukemia. Therefore, we determined the long-term disease-free survival of patients who did not achieve a remission and were then treated with high-dose therapy and bone marrow allografting from matched sibling donors. Twenty-one patients (median age, 28 years) who did not achieve a remission with induction chemotherapy were subsequently treated with allogeneic BMT. After BMT, 90% achieved a complete remission. Six died of complications of the therapy, and six patients relapsed between 27 and 448 days after BMT. Nine patients (43%; median age, 25 years) are alive between 556 and 4,174 days after BMT. The cumulative probability of disease-free survival at 10 years is 43%. This study suggests that allogeneic BMT can be an effective therapy to achieve long-term control of acute leukemia, even in those patients who do not achieve a remission with primary therapy.

1989 ◽  
Vol 7 (6) ◽  
pp. 747-753 ◽  
Author(s):  
P Bordigoni ◽  
J P Vernant ◽  
G Souillet ◽  
E Gluckman ◽  
D Marininchi ◽  
...  

Thirty-two children ranging in age from 1.5 to 16 years with poor-prognosis acute lymphoblastic leukemia (ALL) were treated with myeloablative immunosuppressive therapy consisting of cyclophosphamide (CPM) and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) while in first complete remission (CR). The main reasons for assignment to BMT were WBC count greater than 100,000/microL, structural chromosomal abnormalities, and resistance to initial induction therapy. All children were transplanted with marrow from histocompatible siblings. Twenty-seven patients are alive in first CR for 7 to 82 months post-transplantation (median, 30 months). The actuarial disease-free survival rate is 84.4% (confidence interval, 7.2% to 29%) and the actuarial relapse rate is 3.5% (confidence interval, 0.9% to 13%). Four patients died of transplant-related complications, 16 developed low-grade acute graft-v-host disease (GVHD), and six developed chronic GVHD. The very low incidence of relapse (one of 28 long-term survivors) precluded the determination of the prognostic significance of the different poor-outcome features. Moreover, two infants treated with busulfan, CPM, and cytarabine (Ara-C) relapsed promptly in the marrow. In summary, as a means of providing long-term disease-free survival and possible cure, BMT should be considered for children with ALL presenting poor-prognostic features, particularly certain chromosomal translocations [t(4;11), t(9;22)], very high WBC counts, notably if associated with a non-T immunophenotype, and, perhaps, a poor response to initial therapy with corticosteroids (CS), or infants less than 6 months of age.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4419-4419
Author(s):  
Je-Jung Lee ◽  
Yu-Ra Lee ◽  
Hee-Nam Kim ◽  
Nan-Young Kim ◽  
Kyeong-Soo Park ◽  
...  

Abstract Since the introduction of high-dose cytarabine therapy, there are still controversies for the role of allogeneic or autologous stem cell transplantation (SCT) in acute myeloid leukemia (AML), but the SCT, especially allogeneic, has a benefit in AML patients with intermediate risk. However, it is needed to investigate for a new prognostic factor, in addition to the cytogenetics, to the further stratifying approach. Internal tandem duplications (ITD) within FLT3 are present in 20–30% of patients with AML and have a prognostic implication in the disease. However, there was no report in AML patients who underwent allogeneic bone marrow transplantation (BMT). In this study, we evaluated the prognostic relevance of FLT3/ITD in 42 patients with AML who underwent allogeneic BMT. FLT3/ITD mutations were studied on bone marrow samples at diagnosis using PCR. As a baseline study, we firstly analyzed the incidence of FLT3/ITD in BM samples at diagnosis of 214 patients with AML. Of the patients, FLT3/ITD were found in 68 patients (31.8%). In this study, 64% of the patients who underwent allogeneic BMT were positive for FLT3/ITD mutations. Methologically, FLT3/ITD detections by melting curve analysis showed higher sensitivity (66.7%) than those by gel electrophoresis (61.9%). There were no significant differences in the engraft periods and the incidence of acute and chronic GVHD according to the presence of FLT3/ITD mutations. When we analyze patient’s survival according to the presence or absence of FLT3/ITD, the probability of overall survival (OS) at 3 years in the AML patients with FLT3/ITD tended to be shorter than those lacking FL3/ITD (53.9 ± 9.9% vs. 60.6 ± 14.7%, P=0.46). In addition, the probability of disease free survival (DFS) at 3 years in the AML patients with and without FLT3/ITD was 57.3±10.3% and 85.7±13.2%, respectively (P=0.046). Among the cytogenetic risk group, low-risk and high-risk groups were no significant differences according to FLT3/ITD despite of the limited number of patients studied. However, patients with intermediate-risk were significantly shorter DFS in the presence of FLT3/ITD than those in the absence of FLT3/ITD (P=0.048). These findings suggest that the presence of FLT3/ITD mutations is a poor prognostic factor for disease free survival in AML patients, especially with cytogenetically intermediate-risk, who underwent allogeneic BMT and melting curve analysis to detect the presence of FLT3/ITD mutations is a useful tool with high sensitivity.


Blood ◽  
1984 ◽  
Vol 63 (3) ◽  
pp. 649-656 ◽  
Author(s):  
R Dinsmore ◽  
D Kirkpatrick ◽  
N Flomenberg ◽  
S Gulati ◽  
N Kapoor ◽  
...  

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.


Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 381-388 ◽  
Author(s):  
R Dinsmore ◽  
D Kirkpatrick ◽  
N Flomenberg ◽  
S Gulati ◽  
N Kapoor ◽  
...  

Fifty-two patients with acute lymphoblastic leukemia (ALL) underwent allogeneic bone marrow transplantation following cytoreduction with total body irradiation and cyclophosphamide. Twenty-two patients were in second remission, 15 in a later remission, and 15 were in relapse at the time of the transplant. At a median follow-up of 24 mo, 14 of those in second remission survive in continuous remission compared to 5 in later remission and 4 in the relapse group. Statistical analysis showed an improved disease-free survival for the second remission group (p = 0.09). Patients transplanted in later remission or relapse had a similar survival. The improved survival in second remission resulted from a decreased relapse rate posttransplant, as the early mortality from nonleukemic causes was similar among the groups (p = 0.01). In the second remission patients, no characteristics of the initial leukemia were identified that significantly affected outcome. In the combined later remission and relapse group, poor prognosis posttransplant was associated with initial WBC greater than 20K, age at diagnosis older than 10, or initial remission duration less than or equal to 1 yr. These results suggest that extended disease-free survival may be achieved by second remission transplantation and that improved therapy is necessary for later remission or relapse transplants due to the high rate of posttransplant relapse.


Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1923-1927 ◽  
Author(s):  
NJ Chao ◽  
SJ Forman ◽  
GM Schmidt ◽  
DS Snyder ◽  
MD Amylon ◽  
...  

Abstract Fifty-three patients with high-risk acute lymphoblastic leukemia (ALL) under age 50 with a histocompatible sibling donor received high-dose radiochemotherapy followed by allogeneic bone marrow transplantation (BMT). The high-risk factors used to identify the patients were: white blood cell count at initial presentation, cytogenetic abnormalities, age, extramedullary leukemic infiltration, and time from initial therapy to complete remission. Patients with one or more of the above risk factors who received BMT have a disease-free survival of 61% with a median follow-up of 66 months (range 11 months to 10.6 years), and an actuarial relapse rate of 10%. This study demonstrates that patients with high-risk ALL achieve a significant disease-free survival and cure rate with the use of allogeneic fully matched sibling BMT. However, a properly designed prospective study comparing the outcome of BMT with the best currently available chemotherapy data is required to define the ultimate role of BMT in this group of patients.


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