Second Allogeneic Bone Marrow Transplantation for Patients with Either Graft Failure or Relapsed Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1770-1770
Author(s):  
Stella Santarone ◽  
Erminia Di Bartolomeo ◽  
Pasqua Bavaro ◽  
Paolo Di Carlo ◽  
Paola Olioso ◽  
...  
Keyword(s):  
Graft Failure ◽  
Malignant Disease ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Disease Free ◽  
Median Interval

Abstract Despite myeloablative and immunosuppressive conditioning therapy, allogeneic bone marrow transplantation (BMT) may fail because of either graft failure or relapse of the malignant disease. In this study we have evaluated the impact of second BMT on long-term disease-free survival (DFS) in 42 patients who were transplanted in our institution between January 1983 and March 2005. GRAFT FAILURE. Eleven patients (4 with aplastic anemia, 4 thalassemia major (TM), 3 chronic myeloid leukemia (CML), 2 acute myeloid leukemia (AML), 1 acute lymphoblastic leukemia (ALL), 1 myelodisplastic syndrome (MDS) received a second BMT for graft failure, either primary (n=8) or secondary (n=3). The median age at time of first BMT was 19 years (range, 3 to 42). The median interval between the first and second BMT was 35 days (range, 27 to 532). Donors were the same of the first BMT. They were HLA genotipically identical (n=8) or HLA phenotipically identical (n=1) or 1 antigen mismatched family members. Four patients died for BMT related causes (2 for acute GvHD, 1 for heart failure and 1 for CNS hemorrhage and rejection). Six patients are now living after a median follow-up of 169 months (range, 52 to 202). Five patients are cured and one had an autologous thalassemia reconstitution and is now living under transfusion treatment. RELAPSE. Thirty-one patients (11 with CML, 9 AML, 9 ALL, 1 MDS, 1 TM) were given a second BMT following relapse of the malignant disease. The median age at time of first BMT was 27 years (range, 1 to 43). The median interval between the first and second BMT was 528 days (range, 115 to 5584 ). Thirty patients received the second BMT from the same HLA genotipically identical family member used for the first transplant. One patient was given the first BMT from a matched unrelated donor and the second transplant from an haploidentical brother. The 6 months transplant related mortality (TRM) was 19%. Six patients died for BMT related causes (4 for acute GvHD, 1 for heart failure and 1 for infection and multiorgan failure). Eight patients had leukaemia relapse following second BMT. Five of them died of chemotherapy complications. One of them, who was reinducted into complete remission and received a third BMT from an unrelated donor, died because encephalopathy. Nineteen patients are living after a median follow-up of 72 months (range, 4 to 236). The 5-years probabilities of overall survival and disease free survival (DFS) were 59% and 52% respectively. The 5-years DFS for AML, CML and ALL patients was 72%, 54% and 12% respectively (p=0.03). The 5-years DFS for 17 patients conditioned with TBI and for 13 patients conditioned with busulphan (BU) was 62% and 31% respectively (p=0.09). This study show that many patients may benefit from a second BMT either following graft failure or leukemia relapse with an acceptable TRM. In particular, patients with AML or CML are the best candidates to be cured from second BMT. TBI conditioning regimen gives better results as compared to BU regimen.

Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in first remission: a cooperative study of the Groupe d'Etude de la Greffe de Moelle Osseuse.

1989 ◽  
Vol 7 (6) ◽  
pp. 747-753 ◽  
Author(s):  
P Bordigoni ◽  
J P Vernant ◽  
G Souillet ◽  
E Gluckman ◽  
D Marininchi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Disease Free

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.

scholarly journals Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 677-681 ◽  
Author(s):  
JE Anderson ◽  
FR Appelbaum ◽  
LD Fisher ◽  
G Schoch ◽  
H Shulman ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Severe Neutropenia ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Life Threatening ◽  
Total Body ◽  
Disease Free

Abstract We treated 93 patients with myelodysplastic syndrome using cyclophosphamide and either total body irradiation (n = 88) or busulfan (n = 5) followed by marrow transplantation. Sixty-five marrow donors were genotypically HLA-identical siblings and 28 were other family members or unrelated donors. Before transplantation all patients had either severe neutropenia or thrombocytopenia or had greater than 5% blasts in the marrow or peripheral blood. The probabilities of disease- free survival, relapse, and non-relapse mortality at 4 years were 41%, 28%, and 43%, respectively. Multivariate analysis revealed that younger age and shorter disease duration were significantly associated with improved disease-free survival and decreased non-relapse mortality. Relapse was seen only in patients with excess blasts at the time of transplantation (51% at 4 years). Patients younger than age 40 and without excess blasts had a 4-year disease-free survival of 62%. This study confirms that allogeneic marrow transplantation can cure some patients with myelodysplasia. Because of the favorable outcome in younger patients without excess blasts, we recommend that transplantation be considered early for patients younger than age 40, before disease progression or development of life-threatening cytopenias. For older patients and those with excess blasts, changes in the transplant procedure will be necessary to improve outcome.

Clinical Significance of FLT3 Internal Tandem Duplication in Patients with Acute Myeloid Leukemia Who Underwent Allogeneic Bone Marrow Transplantation.

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 ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Allogeneic Bone Marrow Transplantation ◽  
Melting Curve ◽  
Disease Free Survival ◽  
Melting Curve Analysis ◽  
Allogeneic Bone ◽  
Intermediate Risk ◽  
Free Survival ◽  
Allogeneic Bmt ◽  
Disease Free

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.

scholarly journals Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 677-681 ◽  
Author(s):  
JE Anderson ◽  
FR Appelbaum ◽  
LD Fisher ◽  
G Schoch ◽  
H Shulman ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Marrow Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Severe Neutropenia ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Life Threatening ◽  
Total Body ◽  
Disease Free

We treated 93 patients with myelodysplastic syndrome using cyclophosphamide and either total body irradiation (n = 88) or busulfan (n = 5) followed by marrow transplantation. Sixty-five marrow donors were genotypically HLA-identical siblings and 28 were other family members or unrelated donors. Before transplantation all patients had either severe neutropenia or thrombocytopenia or had greater than 5% blasts in the marrow or peripheral blood. The probabilities of disease- free survival, relapse, and non-relapse mortality at 4 years were 41%, 28%, and 43%, respectively. Multivariate analysis revealed that younger age and shorter disease duration were significantly associated with improved disease-free survival and decreased non-relapse mortality. Relapse was seen only in patients with excess blasts at the time of transplantation (51% at 4 years). Patients younger than age 40 and without excess blasts had a 4-year disease-free survival of 62%. This study confirms that allogeneic marrow transplantation can cure some patients with myelodysplasia. Because of the favorable outcome in younger patients without excess blasts, we recommend that transplantation be considered early for patients younger than age 40, before disease progression or development of life-threatening cytopenias. For older patients and those with excess blasts, changes in the transplant procedure will be necessary to improve outcome.

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 lymphoblastic leukemia

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 381-388 ◽  
Author(s):  
R Dinsmore ◽  
D Kirkpatrick ◽  
N Flomenberg ◽  
S Gulati ◽  
N Kapoor ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Disease Free ◽  
Relapse Group

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.

Clofarabine Salvage Therapy Prior To Allogeneic Hematopoietic Stem Cell Transplantation In Patients With Relapsed Or Refractory AML – Results Of The Bridge Trial –

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 304-304
Author(s):  
Jan Moritz Middeke ◽  
Regina Herbst ◽  
Stefani Parmentier ◽  
Gesine Bug ◽  
Mathias Hänel ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Disease Free Survival ◽  
High Rate ◽  
Unrelated Donor ◽  
Free Survival ◽  
Unrelated Donors ◽  
Disease Free ◽  
Refractory Aml

Abstract Background In relapsed or refractory acute myeloid leukemia (AML) long-term disease-free survival may only be achieved with allogeneic stem cell transplantation (HSCT). However, only about 40% of patients (pts) with relapsed AML receive HSCT. A number of factors contribute to this low rate, among them, a moderate activity of currently available salvage regimens and accumulating toxicity of chemotherapy. Clofarabine is considered to have a favorable risk-benefit ratio in this indication and has been successfully used in conditioning regimens. Our goal was to study the safety and efficacy of a clofarabine salvage therapy as a bridge to HSCT. Here, we report the results of the BRIDGE trial (NCT 01295307), a phase II, multicenter, intent-to-transplant study. Patients and Methods Between March 2011 and May 2013, 84 pts with relapsed or refractory AML older than 40 years were enrolled. Pts were scheduled for at least one cycle of induction therapy with CLARA (clofarabine 30 mg/m2 and cytarabine 1 g/m2 days 1-5). Pts with a donor received HSCT in aplasia after first CLARA. In case of a prolonged donor search HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine 30 mg/m2 day -6 to -3 and melphalan 140 mg/m2 on day -2. In pts with partially matched unrelated donors ATG (Genzyme) at a cumulative dose of 4.5 mg/kg was recommended. GvHD prophylaxis consisted of CsA and mycophenolate mofetil. Results Median age was 61 years (range 40 – 75). Forty-four pts suffered from relapsed AML and 40 pts had refractory disease. According to the current ELN risk stratification 17% of pts were classified as favorable risk, 35% as interm. I, 17% as interm. II and 20% as adverse risk. Complex and monosomal karyotypes were present in only 12% and 10% of pts, respectively. FLT3, NPM1 and CEPBA mutations were found in 16%, 24%, and 4% of the pts. The mean value of the HCT-CI score was 1.6 (range 0 - 7) at the time of study enrollment and 2.3 (range 0 - 7) at the time of conditioning. The overall response rate assessed at day 15 after start of CLARA was 80% (46% good response defined as less than 10% blast in the bone marrow (BM) and 33% moderate response with at least a marked reduction in BM blasts or BM cellularity and absence of blast in the peripheral blood). Seventeen pts did not respond to CLARA and were subsequently treated off study. Due to early death, three pts were not evaluable for treatment response. Overall, 66% of the pts received HSCT within the trial. Donors were HLA-identical siblings in eight pts (14%), HLA-compatible unrelated donors in 30 pts (55%) and unrelated donors with one mismatch in 17 pts (31%). Treatment success defined as complete remission, CR with incomplete recovery or >95% BM donor chimerism and an absolute neutrophil count >0.5 /nL on day 35 after HSCT was achieved in 62% of the pts. Disease-free survival (DFS) is shown in Figure 1. With a median follow up of 16 months the OS for all enrolled patients at one year is 51% (95% CI, 39% to 63%). At the time of enrollment, 14% had a related donor and 33% had an unrelated donor. In 46% of the pts donor search was initiated at the time of enrollment. For 7% of pts donor search was not successful. Time from study entry to HSCT was remarkably low with a median of 33 days (range 19 – 116 days). Of note, time interval did not differ between related and unrelated donors (Figure 2). Day 30 and day 100 mortality, which covered salvage therapy and HSCT, was 9% and 27%, respectively. Six out of seven pts who died within the first 30 days hat refractory AML and thus entered the trial already with a history of long-lasting neutropenia. Liver toxicity was the most frequent adverse event. Fifty percent of the pts had transiently elevated liver enzymes CTCAE grade III considered to be related to clofarabine. Twenty-one patients developed CTCAE grade III – IV sepsis throughout the study treatment. GvHD grade II – IV and III-IV until day 100 after HSCT occurred in 36% and 21% of the pts, respectively. Conclusions This intent-to transplant study allows for a realistic estimate for the outcome of elderly pts with relapsed or refractory AML. We demonstrate a high rate of leukemia-control by CLARA. Fast unrelated donor search and work up and conditioning with clofarabine and melphalan in aplasia allowed for a high rate of successful HSCTs. While the long-term results require longer follow-up the overall results are promising. Disclosures: Middeke: Genzyme: Speakers Bureau. Schetelig:Genzyme: Research Funding. Off Label Use: Clofarabine, not approved for AML.

scholarly journals Allogeneic bone marrow transplantation for high-risk acute lymphoblastic leukemia during first complete remission

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1923-1927 ◽  
Author(s):  
NJ Chao ◽  
SJ Forman ◽  
GM Schmidt ◽  
DS Snyder ◽  
MD Amylon ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Allogeneic Bone ◽  
Free Survival ◽  
Disease Free

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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