Abstract
The coexistence between Chronic Myeloproliferative Syndrome (CMS) and Chronic Lymphoproliferative syndrome (CLS) is a rare event with a few cases reported in literature. This association generates the hypothesis about whether both syndromes derive from the same malignant clonal cells or from independent ones with a common leukemogenic stimulus. In some cases both diseases occur simultaneously while others develop sequentially after exposure to alkylating agents or radiation therapy. We report four patients treated at our center who developed both myeloproliferative and lymphoproliferative syndromes. The CMS were two cases of Myelofibrosis (MF) and two cases of Chronic Myeloid Leukemia (CML). The CLS were two cases of Chronic Lymphocytic Leukemia (CLL), one case of Follicular Lymphoma and one case of Hairy Cell Leukemia. Patient A is a 66-year-old man who was diagnosed with CLL. Inmunophenotyping of peripheral blood (PB) and bone marrow (BM) showed CD45, CD19, CD20, CD5, CD23, CD11c, FMC7, CD38 positive cells with lambda light chain restriction. The BM biopsy showed infiltration of CLL with slight increase of reticulin. After six months, he developed severe tricytopenia. A new BM biopsy showed morphologically abnormal megakaryocytes and increased reticulin compatible with MF plus coexistence of CLL. Heterozygous JAK2 V617F mutation was detected in PB. Nuclear Magnetic Resonance was compatible with MF. He was treated with rituximab with disappearance of the leukemic clone. Treatment with thalidomide (50 mg/day) and dexamethasone (4 mg/day) was started because of rapidly progressing idiopathic MF. Nowadays we observe an improvement of the hematological counts. Patient B is an 88-year-old woman diagnosed with Philadelphia (Ph)-positive CML in chronic phase who was treated with hydroxyurea (500–1000 mg/day). Twenty months later, she developed CLL with inmunophenotyping of PB and BM lymphocytes positives for CD5, CD19, CD20, CD22 and CD23 with kappa light chain restriction. The 13q14 deletion was detected by FISH in the lymphoid cells. The BCR/ABL rearrangement by FISH was observed in all myeloid elements but none in the lymphoid cells. The patient started with chlorambucil (10 mg/m2/day for 15 days per month for 10 months). Patient C is a 73-year-old man who was simultaneously diagnosed with Ph+ CML and Follicular Lymphoma. He was treated with hydroxyurea for the CML and subsequently imatinib was started. At present, 7 years after the initial diagnosis, he developed a blast crisis. Patient D is a 50-year-old woman who was diagnosed with MF with myeloid metaplasia. Physical examination revealed splenomegaly. BM inmunophenotyping was normal. The patient received splenic irradiation, prednisone and thalidomide showing recovery of hematological counts. After 3 years she developed Hairy Cell Leukemia with inmunophenotyping of PB positive for CD45, CD19, CD20, CD11c, CD23, CD25, CD103, HLA-DR and CD79b with lambda light chain restriction. Some authors suggest that this association between CMS and CLS can be originated from a same pluripotent stem cell. Others suggest that coexistence between CMS and CLS is secondary to proliferation of two different progenitors, perhaps, under a single leukemogenic stimulus. Based on the incidence of these diseases, others propose that coexistence is a matter of chance. Of the 4 patients above mentioned, only patient B showed the independent origin of both disorders. As far as we know, this is one of the few reports in which cytogenetic, FISH and molecular studies shows CLL development during the course of CML, arising from a distinct Ph-positive stem cell. Although chemotherapy may increase the risk of secondary malignancies, this is not the case for patients A, B and C since they had not received any treatment before the diagnosis of the second pathology.
We find that further investigation is needed to understand the mechanisms that originate the association of this disorders.
Lymphoblastic leukemia with surface light chain restriction: A diagnostic dilemma