TY - JOUR
T1 - Therapy related-chronic myelomonocytic leukemia (CMML)
T2 - Molecular, cytogenetic, and clinical distinctions from de novo CMML
AU - Patnaik, Mrinal M.
AU - Vallapureddy, Rangit
AU - Yalniz, Fevzi F.
AU - Hanson, Curtis A.
AU - Ketterling, Rhett P.
AU - Lasho, Terra L.
AU - Finke, Christy
AU - Al-Kali, Aref
AU - Gangat, Naseema
AU - Tefferi, Ayalew
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2018/1
Y1 - 2018/1
N2 - Therapy related myeloid neoplasms (t-MN) including therapy related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML) are associated with aggressive disease biologies and poor outcomes. In this large (n = 497) and informative (inclusive of molecular and cytogenetic information) chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key biological insights and an independent prognostic impact for t-CMML. T-CMML was diagnosed in 9% of patients and occurred approximately 7 years after exposure to prior chemotherapy and/or radiation therapy. In comparison to de novo CMML, t-CMML patients had higher LDH levels, higher frequency of karyotypic abnormalities and had higher risk cytogenetic stratification. There were no differences in the distribution of gene mutations and unlike t-MDS/AML, balanced chromosomal translocations, abnormalities of chromosome 11q23 (1%) and Tp53 mutations (<2%) were uncommon. Molecularly integrated CMML prognostic models were not effective in risk stratifying t-CMML patients and responses to hypomethylating agents were dismal with no complete responses. Median overall (OS) and leukemia free survival (LFS) was shorter for t-CMML in comparison to d-CMML (Median OS 10.9 vs 26 months and median LFS 50 vs 127 months) and t-CMML independently and adversely impacted OS (P =.0001 HR 2.1 95% CI 1.4-3.0). This prognostic impact was retained in the context of the Mayo Molecular Model (P =.001, HR 2.4, 95% CI 1.5-3.7) and the GFM prognostic model (P <.0001, HR 2.15, 95% CI 1.5-3.7). In summary, we highlight the unique genetics and independent prognostic impact of t-CMML, warranting its inclusion as a separate entity in the classification schema for both CMML and t-MN.
AB - Therapy related myeloid neoplasms (t-MN) including therapy related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML) are associated with aggressive disease biologies and poor outcomes. In this large (n = 497) and informative (inclusive of molecular and cytogenetic information) chronic myelomonocytic leukemia (CMML) patient cohort, we demonstrate key biological insights and an independent prognostic impact for t-CMML. T-CMML was diagnosed in 9% of patients and occurred approximately 7 years after exposure to prior chemotherapy and/or radiation therapy. In comparison to de novo CMML, t-CMML patients had higher LDH levels, higher frequency of karyotypic abnormalities and had higher risk cytogenetic stratification. There were no differences in the distribution of gene mutations and unlike t-MDS/AML, balanced chromosomal translocations, abnormalities of chromosome 11q23 (1%) and Tp53 mutations (<2%) were uncommon. Molecularly integrated CMML prognostic models were not effective in risk stratifying t-CMML patients and responses to hypomethylating agents were dismal with no complete responses. Median overall (OS) and leukemia free survival (LFS) was shorter for t-CMML in comparison to d-CMML (Median OS 10.9 vs 26 months and median LFS 50 vs 127 months) and t-CMML independently and adversely impacted OS (P =.0001 HR 2.1 95% CI 1.4-3.0). This prognostic impact was retained in the context of the Mayo Molecular Model (P =.001, HR 2.4, 95% CI 1.5-3.7) and the GFM prognostic model (P <.0001, HR 2.15, 95% CI 1.5-3.7). In summary, we highlight the unique genetics and independent prognostic impact of t-CMML, warranting its inclusion as a separate entity in the classification schema for both CMML and t-MN.
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U2 - 10.1002/ajh.24939
DO - 10.1002/ajh.24939
M3 - Article
C2 - 29023992
AN - SCOPUS:85032968327
SN - 0361-8609
VL - 93
SP - 65
EP - 73
JO - American journal of hematology
JF - American journal of hematology
IS - 1
ER -