Myeloproliferative and lymphoproliferative malignancies occurring in the same patient: a nationwide discovery cohort

Abstract

Myeloid and lymphoid malignancies are postulated to have distinct pathogenetic mechanisms. The recent observation that patients with a myeloproliferative neoplasm have an increased risk of developing lymphoproliferative malignancy has challenged this assumption. We collected a nationwide cohort of patients with both malignancies. Patients diagnosed in 1990-2015 were identified through the national Danish Pathology Registry. We identified 599 patients with myeloproliferative neoplasm and a concomitant or subsequent diagnosis of lymphoma. Histopathological review of the diagnostic samples from each patient led to a final cohort of 97 individuals with confirmed dual diagnoses of myeloproliferative neoplasm and lymphoma. The age range at diagnosis was 19-94 years (median: 71 years). To avoid the inclusion of cases of therapy-induced myeloproliferative neoplasm occurring in patients previously treated for lymphoma, only patients with myeloproliferative neoplasm diagnosed unequivocally before the development of lymphoma were included. The average time interval between the diagnoses of the two malignancies was 1.5 years. In the majority of patients (90%) both diagnoses were established within 5 years from each other. Among the lymphoma entities, the frequency of peripheral T-cell lymphomas was markedly increased. Interestingly, all but one of the T-cell lymphomas were of angioimmunoblastic type. These findings suggest that myeloproliferative neoplasm and lymphoproliferative malignancy developing in the same patient may have common pathogenetic events, possibly already at progenitor level. We believe that the molecular characterization of the newly developed biorepository will help to highlight the mechanisms driving the genesis and clonal evolution of these hematopoietic malignancies.

Figure 1.

Flowchart illustrating the establishment of the cohort. DPR: the Danish pathology register; MPN: myeloproliferative neoplasms; LM: lymphoproliferative malignancy.

Figure 2.

Swimmer plots showing, for each patient, for three selected lymphoid diagnoses the chronological occurrence of the myeloproliferative and lymphoproliferative malignancies. Each bar represents one patient in the study. Dark gray parts of the bars represent the time between the diagnosis of the myeloproliferative neoplasm and the lymphoma diagnosis. Light gray parts of the bars represent time with both diagnoses to death or last follow-up. PTCL: peripheral T-cell lymphoma; DLBCL: diffuse large B-cell lymphoma; CLL: chronic lymphocytic leukemia/small lymphocytic lymphoma.

Figure 3.

Survival analyses. Kaplan Meier estimates of overall survival in (A) patients with diffuse large B-cell lymphoma with and without a previous diagnosis of a myeloproliferative neoplasm and (B) patients with peripheral T-cell lymphoma with and without a previous diagnosis of a myeloproliferative neoplasm. DLBCL: diffuse large B-cell lymphoma; MPN_ myeloproliferative neoplasm; PTCL: peripheral T-cell lymphoma; AITL: angioimmunoblastic T-cell lymphoma.