Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide

Abstract

A prospective randomized study was conducted comparing two conditioning regimens for the treatment of patients with chronic myeloid leukemia in chronic phase by marrow transplantation from HLA identical siblings. Sixty-nine patients received 60 mg/kg of cyclophosphamide on each of 2 successive days followed by 6 fractions of total body irradiation each of 2.0 Gy (CY-TBI), and 73 patients received 16 mg/ kg of busulfan delivered over 4 days followed by 60 mg/kg CY on each of 2 successive days (BU-CY). There was no significant difference between the CY-TB1 and the BU-CY groups in the 3-year probabilities of survival (0.80 for both), relapse (0.13 for both), or event-free survival (CY-TBI, 0.68; BU-CY, 0.71) or in speed of engraftment or incidence MARKED IMPROVEMENT in the results of marrow transplantation for treatment of chronic myeloid leukemia (CML) in chronic phase (CP) has been reported over the past 10 years."4 A major factor in producing this improvement was the introduction of a regimen using both methotrexate (MTX) and cyclosporine (CSP) for the prevention of acute graft-versus-host disease (GVHD).' Most regimens used for transplant conditioning during this period included total body irradiation (TBI), and the most widely used such regimen was cyclophosphamide (CY) administered at a dose of 60 m g k g on each of 2 successive days, followed by 2.0 Gy of TB1 administered on each of 6 successive days (CY-TBI).' In 1987, Tutschka reported the use of a conditioning regimen consisting of busulfan (BU; 16 mg/kg administered over 4 days), followed by 60 m g k g CY on each of 2 successive days (BU-CY).' This regimen had low toxicity, was effective in facilitating allogeneic engraftment, and appeared to be particularly effective in the treatment of patients with myeloid malignancy. Although this regimen has been used increasingly in the treatment of patients with CML in CP,' no formal comparison with the CY-TB1 regimen has been reported. In 1988, we began a randomized study comparing these regimens in patients receiving marrow transplants from HLA-identical related donors for the A From The Fred Hutchinson Cancer Reseurch Center and the Vet-The pUblicUtiCJn costs of this article were defruved in part by page charge payment. This urticle must therefore he herebv marked "advertisement" in accorhnce with 18 U.S.C. section 1734 solel)) to indicate this juct. S e d r , WA, 98104-2092. 0 1994 by The Americun Society qf Hemutoiogy. 0006-497//94/8406-0022$3.00/0 2036 of venocclusive disease of the liver. The 4-year probabilities of survival and event-free survival for patients transplanted within 1 year of diagnosis were 0.86 and 0.72, respectively, for each group. Significantly more patients in the CY-TB1 group experienced major creatinine elevations. There was significantly more acute graft-versus-host disease in the CY-TB1 group. Fever days, positive blood cultures, hospitalizations, and inpatient hospital days were significantly more common in the CY-TB1 group than in the BU-CY group. In conclusion, the BU-CY regimen...

Conditioning regimens for allogeneic hematopoietic stem cell transplants in acute myeloid leukemia

“…4 A prospective randomized study has compared 12 Gy with 15.75 Gy TBI, relapse rate (RR) was lower with 15.75 Gy TBI, but non relapse mortality (NRM) and GVHD were higher, leading to comparable overall survival (OS). 5 Combinations of TBI-based regimens are summarized in Table 1.…”

Relationship of Body Mass Index and Arm Anthropometry to Outcomes after Pediatric Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

“…Transplantation preparative regimens included either chemotherapy or chemoradiotherapy as described previously [6][7][8][9][10]. Most chemotherapy-only E-mail address: ksbaker@fhcrc.org (K.S.…”

“…regimens used cyclophosphamide 50 mg/kg/day for 4 days combined with busulfan 4 mg/kg/day for 4 days [6,8]. Most of the busulfan and cyclophosphamide doses were calculated using adjusted body weight if the patient's actual weight was >100% of ideal body weight, when dosing was based on per-kilogram weight.…”

“…Most TBI regimens included cyclophosphamide 60 mg/kg/day for 2 days. Between 1985 and 2000, TBI was delivered from dual opposing cobalt-60 sources at a dose rate in air of 5-8 cGy/min as fractionated TBI, with exposures of 2.0-2.75 Gy for 6-7 consecutive days or hyperfractionated exposures of 1.2 Gy 2-3 times daily for 4 consecutive days [6,9,10]. Starting in 2001, TBI has been delivered by a linear accelerator.…”

FK506 in combination with methotrexate for the prevention of graft- versus-host disease after marrow transplantation from matched unrelated donors

“…Severe veno-occlusive disease (VOD) has been previously defined.'? Hypertension was defined as a diastolic blood pressure >90 mm Hg or a systolic blood pressure > 140 mm Hg sustained for more than 3 plant creatinine clearance was <60 mL/min, if the total bilirubin or SGOT/SGPT was > 1.5 times the upper limit of normal, or if FCV or FEV was <70% of predicted. In addition, patients were excluded if they carried any of the human immunodeficiency viruses or received T-cell-depleted marrow.…”