Cyclophosphamide, cytosine arabinoside and TBI as a conditioning regimen for allogeneic bone marrow transplantation in patients with leukemia

Abstract

Summary:This is a prospective study designed to determine the toxicity, efficacy and antileukemic effect of high-dose cytosine arabinoside (ara-C), cyclophosphamide and total body irradiation (TBI) as a myeloablative regimen prior to allogeneic bone marrow transplantation for patients with hematologic malignancies. Fifty-eight patients with hematologic malignancies were treated with cyclophosphamide, high-dose ara-C and total body irradiation (TBI) followed by allogeneic bone marrow transplantation. Fifty patients had good prognosis disease and eight had poor prognosis disease. Cyclosporine and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. The conditioning regimen consisted of ara-C 3000 mg/m 2 twice a day × six doses on days −7, −6, and −5; cyclophosphamide 1800 mg/m 2 on days −4 and −3; and TBI 1400 cGy midline dose at 5 cGy/min in eight total fractions administered twice a day on days −4, −3, −2, and −1. The bone marrow was infused on day 0 (zero). Toxicity related to the conditioning regimen was comparable to that reported with other conditioning regimens, except for diarrhea which appears to be more frequent. The actuarial survival at 1 year was 69% (58-82) and at 5 years was 54% (42-69) with the numbers in parentheses representing the 95% confidence interval of the KaplanMeier estimate. After a median follow-up of 28 months, 31 of 58 (53%) patients are alive without evidence of disease. Only four of the 58 patients (7%) have relapsed. Cyclophosphamide, ara-C and TBI is a safe and effective myeloablative regimen for patients with leukemia. The overall relapse rate in our study was 7% with a median follow-up of 28 months and appears to be lower than relapse rates reported in other series. This is probably due to the added antileukemic effect of ara-C. This regimen should be compared with other myeloablative regimens in a controlled study.

Fludarabine, amsacrine, high-dose cytarabine and 12 Gy total body irradiation followed by allogeneic hematopoietic stem cell transplantation is effective in patients with relapsed or high-risk acute lymphoblastic leukemia

“…However, intensification of conditioning therapy before allogeneic HSCT could still be a viable approach to improve outcome, especially in young adults suffering from high-risk ALL. The composition of the intensified conditioning regimens has been rather conservative in the past, adhering basically to the standard of cyclophosphamide/TBI with the additional use of VP-16 or Ara-C. 17,[31][32][33][34] Here, we report on the first 15 patients with high-risk or refractory ALL who received allogeneic matched unrelated donor or matched sibling donor HSCT after myeloablative conditioning using a novel and more intensive conditioning regimen called FLAMSA-ATG-TBI. Our primary purpose was to evaluate practicability, safety and complication profile of this regimen as a myeloablative conditioning therapy.…”

“…Time to leukocyte engraftment was 18 days (median, range, 13-34 days) and thereby comparable with other intensified conditioning regimens such as cyclophosphamide/TBI/ Ara-C 32 and cyclophosphamide/TBI/VP-16. 32,39,40 With 60% patients suffering from grade III/IV (6 III, 3 IV) infectious complications during aplasia, infections were the main risks for our patients within the early post transplant phase. But, there was no case of TRM due to infectious complications.…”

“…Grades III-IV nausea/vomiting was seen in 33%, grades III-IV mucositis in 46% and grades III-IV diarrhea in 33%, which was higher than in earlier studies with cyclophosphamide/TBI/ Ara-C or cyclophosphamide/TBI/VP-16. 32,39,40 However, no patient required preventive intubation or experienced aspiration pneumonia. Life-threatening toxicities other than infections did not accumulate.…”

Effect of induced GVHD in leukemia patients relapsing after allogeneic bone marrow transplantation: single-center experience of 33 adult patients

“…All patients except one had under- ). 20 GVHD prophylaxis after BMT consisted of CsA and a short course of MTX. 21 …”

Significance of additional high-dose cytarabine in combination with cyclophosphamide plus total body irradiation regimen for allogeneic stem cell transplantation

“…[1][2][3][4] Intensification of the conditioning regimen using high-dose cytarabine (HDCA) has been investigated as possibly reducing disease relapse in hematological malignancies. Some studies are encouraging additional HDCA, [5][6][7][8][9][10][11] whereas others are reporting more toxicity using HDCA particularly on the heart and lung. [12][13][14][15][16] Our previous preliminary report did not show any significant differences between CY þ TBI and CA þ CY þ TBI in a small cohort.…”