title: Treatment-related deaths and second cancer risk after autologous stem-cell transplantation for Hodgkin's disease.
abstract: Autologous stem-cell transplantation has become a widely used therapy in Hodgkin's disease (HD). To appreciate the early and late risks associated with this procedure, its lethal toxicity and effects on the incidence of secondary cancers were studied. Data related to 467 French patients grafted from 1982 to 1995 for primary sensitive disease (PSD, 22%), primary refractory disease (PRD, 18%), first relapse (R1, 45%), or subsequent relapses (R2, 15%) were analyzed. Grafted patients (PSD, PRD, and R1; n = 393) were matched (3 controls for 1 case) on age, gender, clinical stage, B symptoms, and time at risk with 1179 conventionally treated patients issued from international databases. The proportional hazards (Cox) model was used to assess relative risks (RR). Among grafted patients, 8% died of toxicity related to the procedure, and 18 secondary cancers occurred leading to a 5-year cumulative incidence rate of 8.9%. In this series, risk factors for second cancer were age >/=40 years (RR = 3.73, P = .007) and the use of peripheral blood stem cells as source of graft (RR = 3.10, P = .03). Among grafted and matched ungrafted patients, risk factors for the development of secondary cancer were age >/=40 years (RR = 2.90, P < .001), relapse versus no relapse (RR = 5.22, P = .006), PRD versus other patients (RR = 3.86, P = .033), and grafted versus ungrafted patients (RR = 2.04, P = . 024). Solid tumors were more frequent in grafted than in ungrafted patients (RR = 5.19, P = .001) although the incidence of myelodysplasia and acute myeloid leukemia was similar in the two groups. We conclude that high-dose chemotherapy administered as first-line treatment or after relapse is associated with an acceptable toxic death rate. The risk of secondary myelodysplasia or acute myeloid leukemia is not significantly increased after autologous stem-cell transplantation for HD, whereas an increased risk of solid tumors exists. The peripheral blood stem-cell-associated risk of secondary cancer among grafted patients needs further investigations.
authors.affiliation: Hematology Institute, Hôpital Saint-Louis, Paris, France; Clinical Research Unit and INSERM CJF 96-03/GRECAN, Centre Régional François Baclesse, Caen, France; Bone Marrow Transplantation Unit, Institut Paoli-Calmette, Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: André
authors.forename: M
authors.initials: M
authors.lastname: Henry-Amar
authors.forename: D
authors.initials: D
authors.lastname: Blaise
authors.forename: P
authors.initials: P
authors.lastname: Colombat
authors.forename: J
authors.initials: J
authors.lastname: Fleury
authors.forename: N
authors.initials: N
authors.lastname: Milpied
authors.forename: J Y
authors.initials: JY
authors.lastname: Cahn
authors.forename: J L
authors.initials: JL
authors.lastname: Pico
authors.forename: Y
authors.initials: Y
authors.lastname: Bastion
authors.forename: M
authors.initials: M
authors.lastname: Kuentz
authors.forename: G
authors.initials: G
authors.lastname: Nedellec
authors.forename: M
authors.initials: M
authors.lastname: Attal
authors.forename: C
authors.initials: C
authors.lastname: Fermé
authors.forename: C
authors.initials: C
authors.lastname: Gisselbrecht
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D002648:Child; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality*; D006689:Hodgkin Disease / Q000150:complications / Q000188:drug therapy / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D008297:Male; D008466:Mechlorethamine / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000209:etiology*; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011344:Procarbazine / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000379:methods / Q000401:mortality*; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D011241:Prednisone