Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease

• Published in: Bone marrow transplantation (Basingstoke) Vol. 32; no. 2; pp. 165 - 170
• Main Authors: KULKARNI, S, POWLES, R, SANKPAL, S, MELLER, S, PINKERTON, C. R, MEHTA, J, SINGHAL, S, SIROHI, B, TRELEAVEN, J, SASO, R, HORTON, C, ATRA, A, ORTIN, M, RUDIN, C, GOYAL, S
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 02.07.2003
• Subjects: Acute Disease; Adolescent; Adrenal Cortex Hormones - therapeutic use; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Azathioprine; Biological and medical sciences; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Child; Child, Preschool; Chronic Disease; Corticoids; Corticosteroids; Cyclosporine - therapeutic use; Cyclosporins; Dosage and administration; Drug therapy; Female; Graft versus host disease; Graft versus host reaction; Graft vs Host Disease - drug therapy; Graft vs Host Disease - mortality; Hematologic Neoplasms - complications; Hematologic Neoplasms - mortality; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cell Transplantation - mortality; Hematopoietic stem cells; Humans; Immunomodulators; Immunosuppressive agents; Leukemia; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Physiological aspects; Reagents; Recurrence; Retrospective Studies; Risk factors; Stem cell transplantation; Stem cells; Steroids; Survival Analysis; Thalidomide; Thalidomide - therapeutic use; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation, Homologous; Transplants & implants; United Kingdom; Human; Immunopathology; Acute; Stem cell; Treatment efficiency; Hematopoietic cell; Homograft; Graft versus host reaction; GVHD; Immunomodulator; Chemotherapy; Chronic; transplantation; Graft; Thalidomide
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1704033

Thalidomide was used to treat acute (n=21) or chronic (n=59) graft-vs-host disease (GVHD) in 80 haematopoietic stem cell allograft recipients after failure to respond to the combination of cyclosporine and corticosteroids with or without other agents. The median time to onset of acute GVHD was 11 days, and thalidomide was started at a median of 48 days post transplant. In addition to corticosteroids and cyclosporine, 13 patients had also received other agents before thalidomide. None of the patients responded and all died of acute GVHD. For chronic GVHD (limited in 13, extensive in 46), thalidomide was started at a median of 385 days post transplant. In addition to corticosteroids and cyclosporine, 34 patients received azathioprine concomitantly. In all patients, thalidomide was added to the ongoing immunosuppressive regimen. The median duration of therapy with thalidomide was 60 days (range, 11-1210; <2 weeks in 11). In total, 13 patients (22%) had complete response, eight (14%) partial response and 38 (64%) no response. Response rates were comparable for limited (39%) and extensive (33%) chronic GVHD. At a median of 53 months, 19 patients are alive, 13 without evidence of chronic GVHD. Survival was significantly better in patients who responded to thalidomide. The principal causes of death were progressive chronic GVHD (n=29) and relapsed leukaemia (n=7). In conclusion, thalidomide has no activity in acute GVHD, but has some activity in chronic GVHD in combination with other agents.