Aims: Recombinant alpha-interferon (r-IFN) is an effective therapy for chronic myeloid leukaemia (CML), inducing haematological and major cytogenetic response in 70% and 30% of patients, respectively. In this study we have evaluated the significance of bone marrow (BM) histology on the subsequent response to r-IFN therapy, as well as the morphological changes induced by r-IFN within BM.
Methods and results: 73 BM biopsies were studied from 21 patients with Ph1-positive CML in chronic phase at diagnosis and at different times during r-IFN treatment. At diagnosis the probability of achieving a major or complete cytogenetic response was significantly higher in patients with a total marrow cellularity lower than 90% (P = 0.02). During therapy with r-IFN, significant BM changes included disappearance of the CML pattern (P = 0.0002), reduction of M:E ratio (P = 0.0009) and total cellularity (P = 0.0027), and increase in number of terminal megakaryocytes (P = 0.0009) and of fatty tissue regeneration (P = 0.037); only after long-term therapy (mean 20 months), did reticulin fibrosis increase significantly (P = 0.032).
Conclusions: The overall BM morphology in response to treatment displayed different pictures, ranging from persistence of CML (25 biopsies out of 51), to reversion to normal histology (14 out of 51). Persistence of diffuse morphological abnormalities was associated with lack of cytogenetic responsiveness (P = 0.025).