Long-term follow-up of a randomized trial comparing the combination of cyclophosphamide with total body irradiation or busulfan as conditioning regimen for patients receiving HLA-identical marrow grafts for acute myeloblastic leukemia in first complete remission

Blood ◽  
2001 ◽  
Vol 97 (11) ◽  
pp. 3669-3671 ◽  
Author(s):  
Didier Blaise ◽  
Dominique Maraninchi ◽  
Mauricette Michallet ◽  
Josy Reiffers ◽  
Jean Pierre Jouet ◽  
...  
Keyword(s):  
Complete Remission ◽  
Randomized Trial ◽  
Total Body Irradiation ◽  
Conditioning Regimen ◽  
Acute Myeloblastic Leukemia ◽  
Long Term Follow Up ◽  
Total Body ◽  
First Complete Remission

Allogeneic bone marrow transplantation for children with acute myeloblastic leukemia in first complete remission: impact of conditioning regimen without total-body irradiation--a report from the Société Française de Greffe de Moelle.

1994 ◽  
Vol 12 (6) ◽  
pp. 1217-1222 ◽  
Author(s):  
G Michel ◽  
E Gluckman ◽  
H Esperou-Bourdeau ◽  
J Reiffers ◽  
J L Pico ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Complete Remission ◽  
Total Body Irradiation ◽  
Conditioning Regimen ◽  
Total Body ◽  
First Complete Remission ◽  
Risk Of Relapse

PURPOSE To analyze the French experience of chemotherapeutic preparation before human leukocyte antigen (HLA)-identical bone marrow transplantation (BMT) in children with acute myeloblastic leukemia (AML) in first complete remission (CR). PATIENTS AND METHODS The data base used for this study was a French BMT registry for childhood AML. Twenty-three children were conditioned with busulfan and 120 mg/kg cyclophosphamide (Bu-Cy 120 group). Nineteen received busulfan and 200 mg/kg cyclophosphamide (Bu-Cy200 group). During the same time period, 32 patients were prepared with total-body irradiation (TBI group) most often in combination with 120 mg/kg of cyclophosphamide. RESULTS The probability of relapse was 54%, 13%, and 10% for the Bu-Cy120, Bu-Cy200, and TBI groups, respectively (P < .05 in the univariate analysis, log-rank test, 2 df). In the multivariate analysis, a conditioning regimen with Bu-Cy120 was significantly associated with a higher risk of relapse (P = .02; relative risk, 3.62). The probability of transplant-related mortality (TRM) was 0% for Bu-Cy120, 5% for Bu-Cy200, and 10% for TBI. Kaplan-Meier estimations of event-free survival (EFS) were 46% +/- 24%, 82% +/- 18%, and 80% +/- 14%, respectively, for the three groups, with median follow-up durations of 28 months (range, 3 to 78), 31 months (4 to 68), and 48 months (2 to 73). In the multivariate analysis, two factors adversely affected EFS: a conditioning regimen with Bu-Cy120 (P = .07) and a long interval from diagnosis to BMT (> or = 120 days, P = .08). CONCLUSION Bu-Cy120 is a well-tolerated preparation, but results in a high risk of relapse for children with AML in first CR. This high risk of relapse is not observed when the dose of cyclophosphamide is increased to 200 mg/kg.

scholarly journals Long-Term Follow-up of Myeloablative Haploidentical (HID) Peripheral Blood Stem Cell Transplantation and Post-Transplant Cyclophosphamide (PTCy) Following Fludarabine and Total Body Irradiation (TBI)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3368-3368
Author(s):  
Scott R Solomon ◽  
Xu Zhang ◽  
Melhem Solh ◽  
Lawrence E Morris ◽  
H. Kent Holland ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Graft Failure ◽  
Chronic Gvhd ◽  
Single Institution ◽  
Post Transplant ◽  
Long Term Follow Up ◽  
Total Body ◽  
Very High

Abstract Haploidentical donor (HID) transplant with post-transplant cyclophosphamide (PTCy) is being increasingly utilized worldwide. Although the original "Baltimore" protocol employed nonmyeloablative conditioning, there has been increasing interest in the use of myeloablative conditioning (MAC) in an attempt to decrease the risk of disease recurrence and graft failure. We present the long-term follow-up results of 82 consecutive patients receiving a MAC HID transplant at a single institution between 2011-2017, following a uniform protocol of Fludarabine/total body irradiation (TBI) 1200cGy conditioning, PTCy, tacrolimus and mycophenolate mofetil. PBSC was utilized as the graft source for all transplants and graft CD34 dose was capped at 5 x 106/kg. Median patient age was 42 (range 19-61) years. The most common diagnoses were AML (51%) and ALL (33%), and 39% were high/very high disease risk index (DRI). Donor was a child, sibling or parent in 35%, 43% and 22% respectively. Median follow-up time for surviving patients was 37 months. Primary engraftment occurred in all patients, with all patients achieving complete donor T cell and myeloid chimerism by day +30. There were no cases of late graft failure. The cumulative incidence of grade 3-4 acute graft-versus-host disease (GVHD) and moderate-to-severe chronic GVHD was 17% and 22%, respectively. Non-relapse mortality (NRM) was 7% at one year and 12% at three years post-transplant. Overall survival at 1, 2, and 3 years post-transplant was 85%, 72% and 66% respectively (figure 1). Estimated 3-year DFS, current GVHD-, relapse-free survival (CGRFS), conventional GRFS, and relapse was 67%, 62%, 43%, and 21% respectively. DFS at 3-yr was significantly improved in patients with low/intermediate vs high/very high DRI (79% vs. 48%, figure 2) due to a lower risk of relapse (12% vs. 36%). Infectious complications included CMV reactivation in 55% of patients (CMV disease - 2%) and BK virus infection in 38% (severe - 2%). There were no reported cases of EBV lymphoproliferative disease. This large single institution analysis with long-term follow-up confirms the feasibility of Fludarabine/TBI-based MAC HID transplant with PBSC/PTCy in younger adult patients. This is supported by both the high rate of engraftment, low NRM and a 3-yr CGRFS of 62% (suggesting freedom from relapse and need for long-term systemic immunosuppression for GVHD). The achievement of long term DFS in approximately 80% of low/intermediate DRI and half of high/very high DRI patients is promising. Disclosures Solh: ADC Therapeutics: Research Funding; Celgene: Speakers Bureau; Amgen: Speakers Bureau.

scholarly journals Perspectives on the Use of a Medium-Dose Etoposide, Cyclophosphamide, and Total Body Irradiation Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation: The Japanese Experience from 1993 to Present

2019 ◽  
Vol 8 (5) ◽  
pp. 569 ◽  
Author(s):  
Masahiro Imamura ◽  
Akio Shigematsu
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Conditioning Regimen ◽  
Mortality Rates ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Total Body ◽  
First Complete Remission ◽  
Medium Dose

The outcome for adults with acute lymphoblastic leukemia (ALL) treated with chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) is poor. Therefore, allogeneic HSCT (allo HSCT) for adults aged less than 50 years with ALL is performed with myeloablative conditioning (MAC) regimens. Among the several MAC regimens, a conditioning regimen of 120 mg/kg (60mg/kg for two days) cyclophosphamide (CY) and 12 gray fractionated (12 gray in six fractions for three days) total body irradiation (TBI) is commonly used, resulting in a long term survival rate of approximately 50% when transplanted at the first complete remission. The addition of 30 mg/kg (15 mg/kg for two days) etoposide (ETP) to the CY/TBI regimen revealed an excellent outcome (a long-term survival rate of approximately 80%) in adults with ALL, showing lower relapse and non-relapse mortality rates. It is preferable to perform allo HSCT with a medium-dose ETP/CY/TBI conditioning regimen at the first complete remission in high-risk ALL patients and at the second complete remission (in addition to the first complete remission) in standard-risk ALL patients. The ETP dose and administration schedule are important factors for reducing the relapse and non-relapse mortality rates, preserving a better outcome. The pharmacological study suggests that the prolonged administration of ETP at a reduced dose is a promising treatment.

scholarly journals Marrow transplantation for patients with acute lymphoblastic leukemia: a long-term follow-up

Blood ◽  
1983 ◽  
Vol 62 (5) ◽  
pp. 1139-1141 ◽  
Author(s):  
ED Thomas ◽  
JE Sanders ◽  
N Flournoy ◽  
FL Johnson ◽  
CD Buckner ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Lymphoblastic Leukemia ◽  
Actuarial Analysis ◽  
Long Term Follow Up ◽  
Total Body

Twenty-two patients with acute lymphoblastic leukemia in second or subsequent remission and 26 with acute lymphoblastic leukemia in relapse were given cyclophosphamide (60 mg/kg on each of 2 days), total body irradiation (920 rad), and marrow transplants from HLA-identical siblings. With a minimum follow-up of more than 5 yr, an actuarial analysis shows a survival and apparent cure of 27% of the patients transplanted in remission and 15% of the patients transplanted in relapse.

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