The coexistence of chronic lymphocytic leukemia and myeloproliperative neoplasms: A retrospective multicentric GIMEMA experience

Abstract

Although the coexistence of chronic lymphocytic leukemia (CLL) and myeloproliferative neoplasms (MPN) has been sporadically reported in the literature, no systematic studies on this disease association are available. We retrospectively analyzed 46 patients affected by CLL/MPN referred by 15 Italian GIMEMA centers. The aim of this retrospective multicenter study was to define the following: clinico-biological characteristics, possible familiarity, clinical course of both diseases, and influence of MPN chemotherapy on the course of CLL. Among 46 patients, 30 patients were males, 16 patients were females; median age was 71 years. Only one case had familiar CLL. Myeloproliferative disorders consisted of essential thrombocytemia in 18 cases, polycythemia vera in 10 cases, chronic myeloid leukemia in 9 cases, primary myelofibrosis in 6 cases, and MPN/myelodysplastic syndrome in 3 cases. The lymphoproliferative disorder was diagnosed as monoclonal B-cell lymphocytosis in 8 patients and as Binet Stage A CLL in 38 patients. After a median follow-up of 49 months, 9 patients experienced progressive CLL and only 6 patients required treatment after a median of 57.5 months. The biological profile confirmed a subset of low-risk CLL. Twenty patients received chemotherapy for MPN without influence on the course of CLL: lymphocyte counts remained unchanged after 3, 6, and 12 months of treatment. This series is the largest so far reported in literature. The diagnosis of concomitant CLL/MPN is a rare event and lymphoproliferative disorders present a clinical indolent course with a low-risk biological profile. MPN therapy does not interfere with the prognosis of patients with CLL. Am. J. Hematol. 2011. (c) 2011 Wiley-Liss, Inc

Quantification of JAK2V617F mutation by next‐generation sequencing technology

“…Earlier clinical studies have likewise demonstrated a beneficial effect in early stage B-CLL using nonpegylated interferon alpha 2a [3]. The diagnosis of concomitant CLL/MPN is a rare event and in a recent study analysis of prognostic markers for CLL demonstrated that in patients with a coexistent MPN, lymphoproliferative disorders follow a clinically indolent course [4,5].Our patient has achieved a substantial hematologic, molecular and splenic response in his PV after 22 months on low dose Pegasys. Moreover, he has achieved a favorable reduction in the B-cell CLL clonal population and a change in Zap-70 status from indeterminate to negative.…”

Subjects with chronic lymphocytic leukaemia‐like B‐cell clones with stereotyped B‐cell receptors frequently show MDS‐associated phenotypes on myeloid cells

“…In this regard, it should be noted that occurrence of CLL in association with myeloid malignancies has been only sporadically reported (Lai et al, 1999;Barresi et al, 2000;Miller et al, 2001;Aviv et al, 2004), including cases with CLL associated with acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS) (Billstr€ om et al, 1997;Laurenti et al, 2011;Sandes et al, 2012), and/or systemic mastocytosis (Horny et al, 2006); however, no clear genetic link between the two entities has yet been identified.…”

No Evidence for JAK2^V617F Mutation in Monoclonal B Cells in 2 Patients with Polycythaemia Vera and Concurrent Monoclonal B Cell Disorder

“…However, overt lymphocytosis or monoclonal lymphoproliferative disorders are rare in Ph – MPN with approximately 30 reported cases of concomitant B-CLL [10,11,12,13,14,15]. In a recent large retrospective multicentric Italian study among patients with B-CLL and monoclonal B cell lymphocytosis 18 cases of ET and 10 cases of PV were additionally found [16]. Up to now 4 patients with JAK2 V617F -positive Ph – MPN and B-CLL were evaluated for the presence of JAK2 V617F in lymphocytes without definite proof for the presence of JAK2 V617F mutation in the B-CLL cells, although it was suggested in one case [12,13,14,15].…”