TY - JOUR
T1 - High-dose busulfan and thiotepa followed by autologous stem cell transplantation (ASCT) In previously irradiated medulloblastoma patients
T2 - High toxicity and lack of efficacy
AU - Valteau-Couanet, D.
AU - Fillipini, B.
AU - Benhamou, E.
AU - Grill, J.
AU - Kalifa, C.
AU - Couanet, D.
AU - Habrand, J. L.
AU - Hartmann, O.
PY - 2005/12/1
Y1 - 2005/12/1
N2 - We previously demonstrated that Busulfan-Thiotepa (Bu-Thio) and ASCT effectively treated patients with locally relapsed medulloblastoma after surgery and conventional chemotherapy. We thus evaluated the administration of Bu-Thio in patients relapsing after conventional CNS irradiation. Patients were scheduled to receive Busulfan (600mg/ m2) and Thiotepa (900mg/m2) and ASCT. Resection of residual tumour and additional irradiation were performed if necessary and feasible after Bu-Thio. Toxicity was compared to that observed in 35 patients treated without previous CNS irradiation. From 5/88 to 3/02, 15 patients were treated according to this strategy. Toxicity was significantly higher than that observed in unirradiated patients: thrombocytopenia <50 000/mm3 lasting 56 days (13-732) (P=0.02) and 30 days (4-124), respectively, HVOD (10/15 and 12/35 patients, respectively) (P=0.06), neurological toxicity (8/15 vs 3/35 patients) (P=0.01). Tumour response was assessable in seven patients and consisted in two CR, three PR and two NR. Currently, two of 15 patients are alive with no evidence of disease. In conclusion, the toxicity of Bu-Thio was significantly more severe in previously irradiated patients. In spite of a high response rate, this strategy failed to improve the prognosis of previously irradiated patients with a relapse from a medulloblastoma.
AB - We previously demonstrated that Busulfan-Thiotepa (Bu-Thio) and ASCT effectively treated patients with locally relapsed medulloblastoma after surgery and conventional chemotherapy. We thus evaluated the administration of Bu-Thio in patients relapsing after conventional CNS irradiation. Patients were scheduled to receive Busulfan (600mg/ m2) and Thiotepa (900mg/m2) and ASCT. Resection of residual tumour and additional irradiation were performed if necessary and feasible after Bu-Thio. Toxicity was compared to that observed in 35 patients treated without previous CNS irradiation. From 5/88 to 3/02, 15 patients were treated according to this strategy. Toxicity was significantly higher than that observed in unirradiated patients: thrombocytopenia <50 000/mm3 lasting 56 days (13-732) (P=0.02) and 30 days (4-124), respectively, HVOD (10/15 and 12/35 patients, respectively) (P=0.06), neurological toxicity (8/15 vs 3/35 patients) (P=0.01). Tumour response was assessable in seven patients and consisted in two CR, three PR and two NR. Currently, two of 15 patients are alive with no evidence of disease. In conclusion, the toxicity of Bu-Thio was significantly more severe in previously irradiated patients. In spite of a high response rate, this strategy failed to improve the prognosis of previously irradiated patients with a relapse from a medulloblastoma.
KW - Autologous stem cell transplantation
KW - Busulfan
KW - CNS radiotherapy
KW - Medulloblastoma
KW - Thiotepa
UR - http://www.scopus.com/inward/record.url?scp=28544445217&partnerID=8YFLogxK
U2 - 10.1038/sj.bmt.1705162
DO - 10.1038/sj.bmt.1705162
M3 - Article
C2 - 16184181
AN - SCOPUS:28544445217
SN - 0268-3369
VL - 36
SP - 939
EP - 945
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
IS - 11
ER -