Nonhepatosplenic extramedullary manifestations of chronic myelomonocytic leukemia: clinical, molecular and prognostic correlates

Hoversten, Katherine P.; Vallapureddy, Rangit; Lasho, Terra L.; Finke, Christy; Ketterling, Rhett P.; Hanson, Curtis A.; Gangat, Naseema; Tefferi, Ayalew; Patnaik, Mrinal M.

doi:10.1080/10428194.2018.1452212

Cited by 18 publications

(23 citation statements)

References 9 publications

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“…13 Major issues with the 2015, IWG MDS/MPN overlap syndrome response criteria include the fact that i) these criteria are expert consensus recommendations and await rigorous prospective validation, ii) quality of life assessment currently relies on the MPN-SAF and estimation of the TSS, which have been developed for patients with myelofibrosis and need validation/refinement in CMML patients, 18 and iii) the absence of a stable disease category. 19 There is a major effort from the global CMML community to assess investigational agents for the management of this disease, with several drugs undergoing clinical trial assessments, some with early promising results (Table S3). These include targeted agents such as tagraxofusp, a CD123-directed cytotoxin (IL-3 conjugated diphtheria toxin; NCT 02268253) and tipifarnib, a farnesyl transferase inhibitor with activity in RAS wild type CMML (NCT 02807272).…”

Section: Discussionmentioning

confidence: 99%

Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients

et al. 2019

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Hypomethylating agents (HMA) are currently the only FDA approved therapy for patients with chronic myelomonocytic leukemia (CMML). In the current retrospective study, we assessed response rates as adjudicated by the IWG (International Working Group) MDS (myelodysplastic syndrome) and MDS/MPN myeloproliferative neoplasm overlap syndrome response criteria, in 121 CMML patients treated with Azacitidine (AZA, n = 56) and Decitabine (DAC, n = 65). The overall response rates were 41% by the IWG MDS (AZA-45%, DAC-39%), and 56% by the IWG MDS/MPN (AZA-56%, DAC-58%) response criteria, with CR (complete remission) rates of <20% for both agents, by both criteria. There were no significant differences in response rates between proliferative and dysplastic CMML. Moreover, 29% of CMML patients in a CR with HMA progressed to AML (blast transformation), underscoring the limited impact of these agents on disease biology. Progression after HMA response was associated with a median overall-survival (OS) of 8 months, while median OS in patients with primary HMA failure was 4 months. Lower serum LDH levels (<250 Units/L) were associated with HMA responses by both criteria; while ASXL1 and TET2 mutational status had no impact. HMA treated patients had a longer median OS (31 vs 18 months; P = .01), in comparison to those treated with conventional care regimens (excluding observation only patients), without any differences between AZA vs DAC (P = .37). In conclusion, this study highlights the inadequacies of HMA therapy in CMML, retrospectively validates the IWG MDS/MPN response criteria and underscores the need for newer, rationally derived therapies.

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Section: Discussionmentioning

confidence: 99%

Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients

et al. 2019

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“…We were able to find case reports of using hypomethylating agents for CMML associated with leukemia cutis, 35,36 and a few patients treated with AML induction followed by involved field radiation. 37 We employed a strategy similar to MS associated with AML, given that the patient had few comorbidities and a high burden of symptoms. Moreover, given reports that NPM1 is associated with chemo-sensitivity, 38,39 and high CR rates, at least on AML, we extrapolated that a similar response might occur in our case.…”

Section: Discussionmentioning

confidence: 99%

“…7 In a large series of 452 patients reported by the Mayo Clinic, 119 patients had extramedullary manifestations. 8 Of those, 15% had lymphadenopathy, 6% leukemia cutis, 3% gingival infiltrates, and two patients had MS. Few cases of CMML have presented with pericardial effusion or lymph node involvement. 9,10…”

Section: Introductionmentioning

confidence: 97%

Chronic myelomonocytic leukemia associated with myeloid sarcomas and NPM1 mutation: a case report and literature review

Matanes

Abdelazeem

Shah

et al. 2019

Therapeutic Advances in Hematology

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We present a case of chronic myelomonocytic leukemia (CMML) associated with myeloid sarcomas. The CMML also harbored a NPM1 mutation, which is uncommonly described outside the context of acute myeloid leukemia (AML). We describe our treatment strategy, which involved remission-induction chemotherapy that led to rapid resolution of myeloid sarcomas, and we present a literature review highlighting the treatment challenges that similar cases pose.

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“…[3] Extramedullary hematopoiesis (EMH) resulting in splenomegaly, hepatomegaly, and lymphadenopathy can be seen in patients with CMML, with a recent study ( n =452) demonstrating palpable hepatosplenomegaly in 27% of patients at diagnosis; 14% with isolated splenomegaly and 3% with isolated hepatomegaly. [4] The presence of palpable hepatosplenomegaly was associated with a “proliferative” CMML subtype and was found to be independently associated with an inferior overall survival (OS). [4]…”

Section: Introductionmentioning

confidence: 99%

“…[4] The presence of palpable hepatosplenomegaly was associated with a “proliferative” CMML subtype and was found to be independently associated with an inferior overall survival (OS). [4]…”

Section: Introductionmentioning

confidence: 99%

Splenectomy in patients with chronic myelomonocytic leukemia: Indications, histopathological findings and clinical outcomes in a single institutional series of thirty‐nine patients

et al. 2018

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In a 28-year period, 39 (7%) patients with chronic myelomonocytic leukemia (CMML) (median age 66 years, 64% male) underwent a splenectomy at our institution. Primary indications for splenectomy were refractory thrombocytopenia (36%), progressive spleen related symptoms (33%), emergent splenectomy for splenic rupture (21%), refractory anemia (8%), and prior to allogeneic stem cell transplant (3%). Eleven (28%) patients had anemia at the time of splenectomy, of which 3 (27%) were autoimmune. The median time to splenectomy from CMML diagnosis was 6 months (0-40); perioperative morbidity and mortality rates were 43% and 13%, while the median postsplenectomy survival was 25 months (11-38). Durable remission in spleen related symptoms, thrombocytopenia, complications from splenic rupture, and anemia were achieved in 85%, 50%, 62%, and 21% of patients, respectively. Perioperative morbidity (n = 30) included infections/sepsis in 6 (20%), intraabdominal bleeding in 4 (13%), venous thromboembolism (VTE) in 3 (10%), and acute lung injury in 2 (7%) patients. The median duration of hospital stay was 6 days (1-25), with 5 deaths occurring secondary to respiratory failure (n = 2), multiorgan dysfunction (n = 2) and hemorrhagic shock (n = 1). There was no difference in overall survival between CMML patients that underwent splenectomy, in comparison to those that did not. Unlike in myelofibrosis, portal hypertension was not an indication for splenectomy and no patients developed post-splenectomy thrombocytosis. In conclusion, apart from being a lifesaving emergent modality in the event of splenic rupture, splenectomy has an important palliative role in patients with CMML, with significant and durable improvements in spleen related symptoms and refractory cytopenias.

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Nonhepatosplenic extramedullary manifestations of chronic myelomonocytic leukemia: clinical, molecular and prognostic correlates

Cited by 18 publications

References 9 publications

Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients

Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients

Chronic myelomonocytic leukemia associated with myeloid sarcomas and NPM1 mutation: a case report and literature review

Splenectomy in patients with chronic myelomonocytic leukemia: Indications, histopathological findings and clinical outcomes in a single institutional series of thirty‐nine patients

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