Busulfan and cyclophosphamide as a preparative regimen for bone marrow transplantation in patients with prior chest radiotherapy.
In a previous study, we reported that patients with hematologic malignancies who had received prior chest radiotherapy had a 32% risk of developing fatal interstitial pneumonia (IP) when prepared for bone marrow transplantation (BMT) with a regimen containing total body irradiation (TBI). To determine if avoidance of TBI would lessen the incidence of fatal IP, 37 patients who had received prior chest radiotherapy in excess of 2000 cGy were prepared with busulfan (BU, 4 mg/kg x 4 days) and cyclophosphamide (CY, 60 mg/kg x 2 days) followed by autologous (n = 15) or allogeneic (n = 22) BMT. Thirty-five of these patients had recurrent or refractory hematologic malignancies and most were heavily pretreated. Results were compared with the group of similar patients (n = 25) previously treated at our institution with a CY/TBI conditioning regimen. Among those treated with BU/CY, two patients (5%) developed fatal interstitial pneumonia, 12 (32%) died of other transplant related toxicities and 13 (35%) died of relapse. Seven (19%) patients remain alive and well. Among those treated with CY/TBI, eight (32%) died of pneumonia, six (24%) died of relapse, nine (36%) died of other causes and two (8%) remain alive and well. The 5% incidence of fatal interstitial pneumonitis in the chemotherapy conditioned group was significantly less than the 32% incidence in the previously treated CY/TBI group (p = 0.005). However, long-term survival and relapse probabilities were not significantly better than seen previously with CY/TBI, although a trend towards improved survival was observed in the BU/CY group. Avoidance of TBI appeared to lower the incidence of fatal pneumonitis in patients with prior chest radiotherapy.
Van der Jagt
R H
RH
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Appelbaum
F R
FR
Petersen
F B
FB
Bigelow
C L
CL
Fisher
L D
LD
Schoch
G H
GH
Buckner
C D
CD
Sanders
J E
JE
Storb
R
R
Sullivan
K M
KM
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D002066:Busulfan / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D007938:Leukemia / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011292:Premedication; D011658:Pulmonary Fibrosis / Q000453:epidemiology / Q000209:etiology / Q000401:mortality; D012307:Risk Factors; D013909:Thorax / Q000528:radiation effects*; D014916:Whole-Body Irradiation
D003520:Cyclophosphamide; D002066:Busulfan