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Blood, Vol. 92 No. 6 (September 15), 1998:
pp. 1933-1940
Treatment-Related Deaths and Second Cancer Risk After Autologous
Stem-Cell Transplantation for Hodgkin's Disease
Marc André,
Michel Henry-Amar,
Didier Blaise,
Philippe Colombat,
Joël Fleury,
Noël Milpied,
Jean-Yves Cahn,
José-Luis Pico,
Yves Bastion,
Mathieu Kuentz,
Gérard Nedellec,
Michel Attal,
Christophe Fermé, and
Christian Gisselbrecht for the Société Française de Greffe de
Moelle
From the 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;
Hematology Department, Hôpital Bretonneau, Tours, France; Bone
Marrow Transplantation Unit, Centre Jean Perrin, Clermont-Ferrand,
France; Hematology Department, C.H.U. Hôtel-Dieu, Nantes, France;
Hematology Department, Hôpital Jean Minjoz, Besançon,
France; Bone Marrow Transplantation Unit, Villejuif, France; Hematology
Department, Centre Hospitalier Lyon-Sud, Pierre-Bénite; Bone
Marrow Transplantation Unit, Hôpital Henri Mondor, Créteil,
France; Hematology Department, Hôpital Percy, Clamart, France;
Hematology Department, Hôpital Purpan, Toulouse, France.
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.
© 1998 by The American Society of Hematology.
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