Background: Few cases of concurrent CMML and non-Hodgkin lymphoma (NHL) are reported in the literature. A unifying etiology for these neoplasms has not been identified. We hypothesize a shared clonal origin in concurrent or sequential cases of CMML and NHL. Methods: We retrospectively analyzed the medical records of 10 patients (pts) treated at Huntsman Cancer Institute between 2004-2022 with pathologically confirmed NHL and CMML. For each pt, a longitudinal list of somatic mutations detected by institutional hematopoietic next generation sequencing in peripheral blood, bone marrow, or tissue was compiled. Results: Eight pts had NHL diagnosis (dx) preceding CMML dx (2 had absolute monocytosis at the time of NHL dx). Two pts were diagnosed with NHL within 6 months after CMML dx. The median time between NHL and CMML dx was 6 years (Table 1). The median time between NHL dx and onset of absolute monocytosis was 8 months. Seven of 10 pts received anti-cancer therapy prior to the dx of CMML. Five of the 7 pts received alkylating chemotherapy. Two of the 5 pts also received radiation therapy (XRT) and a topoisomerase II inhibitor, respectively. One pt received pelvic XRT for prostate cancer. One of the 7 pts had an 11q23 rearrangement and strong evidence of therapy related CMML (t-CMML). Seven pts were diagnosed with CMML-0 and 1 with CMML-2. Four pts received treatment for CMML, of whom 4 received azacitadine for a median of 1.5 cycles (range 1–7 cycles). Four pts are deceased. Cause of death includes pneumonia (n=2), malignant pleural effusions (n=1), and unknown (n=1). The most frequently detected mutations were in TET2, ASXL1, SRSF2, ETNK1 and BRAF. Non-V600E BRAF and ETNK1 missense mutations were each detected in 4 pts. Conclusion: We report the largest number of pts with concurrent/sequential NHL and CMML. The time between NHL dx and onset of absolute monocytosis was shorter than the time between NHL and CMML dx, suggesting that CMML is underdiagnosed in this population. With only 1 case of t-CMML, the relationship between anti-cancer treatment and CMML pathogenesis remains unclear in the other pts. We will perform targeted sequencing of myeloid and lymphoid cells collected over time to assess for a common mutation that would suggest a shared clonal origin. The longitudinal nature of our analysis may inform our understanding of clonal evolution relative to cancer-related treatments.
Table 1. Patient characteristics.
CLL FISH panel: deletion 11q22, trisomy 12, deletion 13q14, and deletion 17p13 (TP53)
MDS FISH panel: deletion 5q31, monosomy 7, deletion 7q31, trisomy 8, deletion 20q12
MPD FISH panel: 4q12 FIP1L1-PDGFRA Fusion, 5q32 (PDGFRB) Rearrangement, 8p11.2 (FGFR1) Rearrangement, t(9;22) BCR-ABL1 Fusion AML w/MDS, therapy related AML FISH panel: Deletion 5q, Monosomy 7, Deletion 7q, 11q23 (KMT2A) Rearrangement
DLBCL: diffuse large B-cell lymphoma
MCL: mantle cell lymphoma
LPL/WM: lymphoplasmacytic lymphoma/Waldenström macroglobulinemia
MZL: marginal zone lymphoma
CLL: chronic lymphocytic leukemia
PMBCL: primary mediastinal B-cell lymphoma
FL: follicular lymphoma
MBL: monoclonal B-cell lymphocytosis
LGL: large granular lymphocyte leukemia
n/a: not applicable or unknown due to lack of sufficient data in our electronic medical record
R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisoneBR; bendamustine, Rituximab
VRd: bortezomib, rituximab, dexamethasone
ADT: androgen deprivation therapy
ISRT: involved site radiation therapy
FCR: fludarabine, cyclophosphamide, rituximab
DA-EPOCH-R: dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin,
rituximab
R-DHAX: rituximab, dexamethasone, cytarabine, oxaliplatin
FluCy: fludarabine, cyclophosphamide
CAR-T: chimeric antigen receptor T-cell therapy
TPO: thrombopoietin
C: cycle
EPO: Erythropoetin
HMA: hypomethylating agent
CR: complete response
POD: progression of disease
alloHSCT: allogeneic hematopoietic stem cell transplant
