Radiation-associated pneumonitis following autologous stem cell transplantation: predictive factors, disease characteristics and treatment outcomes.
High-dose therapy followed by autologous stem cell transplantation (ASCT) prolongs survival in patients with multiple myeloma and is relatively safe with treatment-related mortality rates of only 1-5%. Interstitial pneumonitis (IP) is normally an infrequent complication of ASCT with a reported incidence of 0-16%. Between 1992 and 1998, 94 myeloma patients at our center underwent ASCT using a high-dose regimen of etoposide (60 mg/kg), melphalan (160 mg/m2) and fractionated TBI 12 Gy. An unusually high incidence of IP (29/94 (31%)) was noted. Mortality in the IP patients was high at 45%. Patients developing IP were more frequently anemic than those who did not have pulmonary complications (hemoglobin <100 g/l) prior to transplant (P = 0.03) but no other pre-transplant factors were predictive (ie age, gender, smoking history, CMV status, pulmonary function, creatinine, beta2-microglobulin or C-reactive protein, prior cumulative chemotherapy or chest irradiation). A significantly lower IP rate was noted in 32 contemporaneous myeloma control patients conditioned with BU-CY without TBI at our center (3/32 (9%); P=0.03) and in 32 lymphoma control patients conditioned with the same melphalan and etoposide regimen minus the TBI (2/32 (6%); P = 0.003). In contrast, when using the same TBI-containing regimen in 32 concurrently treated lymphoma patients, an increase in IP similar to that seen in our myeloma cohort (7/32 (22%); P = 0.3) was noted. This strongly suggests that TBI is the predominant factor contributing to lung toxicity. We conclude that radiation-associated pneumonitis cannot be easily predicted by pretransplant variables. Therefore surveillance, early recognition and prompt therapy are recommended.
University of Toronto Autologous Bone Marrow Transplant Program, The Princess Margaret Hospital, Ontario, Canada.
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Chen
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Abraham
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Tsang
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Crump
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Keating
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AK
Stewart
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D011237:Predictive Value of Tests; D011379:Prognosis; D017564:Radiation Pneumonitis / Q000209:etiology* / Q000503:physiopathology*; D012189:Retrospective Studies; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation / Q000009:adverse effects*
D005047:Etoposide; D008558:Melphalan