Concomitant or Sequential Chronic Lymphocytic Leukemia (CLL) and Chronic Myeloid Leukemia (CML): A Molecular and Clinical Survey

A 75-year-old man presented with B-CLL followed by a CML. We retrospectively analyzed the frozen BM and PB lymphocytes that evidenced 2 distinct clonal proliferations: one is a B CD5⁺/CD19⁺ lymphocyte population, without BCR-ABL fusion; the other is the CD19⁺ mononuclear cell population expressing traces of BCR-ABL, 3 years before the occurrence of CML. We suggest that (1) the emergence of the Ph⁺ clone after the treatment of CLL is probably related to RFC-induced immunosuppression, and (2) the long DFS of CLL might be due to the current TK inhibitor treatment

Full Abstract

Introduction

The coexistence of B-cell chronic lymphocytic leukemia (B-CLL) and chronic myeloid leukemia (CML) is a rare event. This coexistence has led to speculation of the clonal origin of these neoplasms. In some cases, 2 independent clones were demonstrated.

Patients and Methods

A 75-year-old man presented with splenomegaly and enlarged lymph nodes. Immunophenotype (kappa, CD19⁺, CD5⁺, CD23⁺) was compatible with B-CLL. Bone marrow examination showed infiltration by small lymphocytes next to a myeloid and megakaryocytic hyperplasia. Cytogenetic analysis of the marrow showed 46XY, del(16q). Philadelphia chromosome (Ph) was negative. The patient was diagnosed with B-CLL and treated by 6 RFC (rituximab/fludarabine/cyclophosphamide). He reached a molecular remission (MCR), but 3 years after the treatment for CLL, he developed hyperleukocytosis (26000/μL), mainly myeloid cells. Bone marrow smear demonstrated a myeloid hyperplasia with predominance of immature progenitors. The Ph was clearly evidenced, and CML was confirmed. The patient thus received thus imatinib 400 mg/day orally with hematologic but only partial molecular remission at 18 months. A Y25.3H mutation was detected, and the patient was switched to dasatinib with a successful evolution. The CLL remained in MCR during this 5-year period.

Results

To know whether CML is a secondary event induced by RFC treatment or the emergence of a latent CML clone, we analyzed retrospectively the frozen BM and PBL lymphocytes. The results were consistent with the view that there are 2 distinct clonal proliferations: one is a clonal B CD5⁺/CD19⁺ lymphocyte population, without BCR-ABL fusion; the other is the CD19⁺ mononuclear cell population expressing traces of BCR-ABL, 3 years before the occurrence of CML.

Conclusion

Our data provide evidence for a separate clonal origin for each disorder, raising the hypothesis that (1) the emergence of the Ph⁺ clone after the treatment of CLL is probably related to RFC-induced immunosuppression, and (2) the long disease-free survival of CLL might be due to the current tyrosine kinase inhibitor treatment.