Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia: Clinical and Molecular Genetic Prognostic Factors in a Nordic Population

Wedge, Eileen; Hansen, Jakob Werner; Dybedal, Ingunn; Creignou, Maria; Ejerblad, Elisabeth; Lorenz, Fryderyk; Werlenius, Olle; Ungerstedt, Johanna; Holm, Mette; Nilsson, Lars; Kittang, Astrid Olsnes; Antunovic, Peter; Rosenberger, Peter; Andersen, Mette Klarskov; Papaemmanuil, Elli; Bernard, Elsa; Jädersten, Martin; Hellström‐Lindberg, Eva; Grønbæk, Kirsten; Ljungman, Per; Friis, Lone Smidstrup

doi:10.1016/j.jtct.2021.08.028

Cited by 9 publications

(11 citation statements)

References 27 publications

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“…ASXL1, TET2, RUNX1, SRSF2, and RAS were the most frequently mutated genes. Transplantation outcomes were better than those previously reported, with a 5-year OS of 46.5%, NRM of 30%, and RR of 25% (38).…”

Section: A Chronic Myelomonocytic Leukemiacontrasting

confidence: 78%

Allogeneic Hematopoietic Stem Cell Transplantation for Mixed or Overlap Myelodysplastic/Myeloproliferative Disorders

Symeonidis

Chondropoulos²,

Verigou³

et al. 2022

Front. Oncol.

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Chronic myelomonocytic leukemia (CMML) and the remaining, less frequent hybrid, mixed, or overlap myelodysplastic syndromes/myeloproliferative neoplasms (MDSs/MPNs) are difficult to treat neoplastic hematological disorders, exhibiting substantial clinical and prognostic heterogeneity, for which clear therapeutic guidelines or effective treatment options are still missing. CMML has an overall survival ranging from a few months to several years. Although patients with proliferative or dysplastic features may benefit from hydroxyurea and hypomethylating agent treatment, respectively, none of these treatments can establish long-term remission and prevent the inevitable transformation to acute leukemia. Novel targeted treatment approaches are emerging but are still under investigation. Therefore, currently, allogeneic stem cell transplantation (allo-SCT) remains the only treatment modality with a curative potential, but its widespread application is limited, due to significant morbidity and mortality associated with the procedure, especially in the elderly and in patients with comorbidities. Recognition of patient eligibility for allo-SCT is crucial, and the procedure should be addressed to patients with a good performance status without severe comorbidities and mainly to those in intermediate- to high-risk category, with a suitable stem cell donor available. The issues of best timing for performing transplantation, patient and donor eligibility, the type of conditioning regimen, and the outcomes after various allo-SCT procedures are the topics of this review.

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Section: A Chronic Myelomonocytic Leukemiacontrasting

confidence: 78%

Allogeneic Hematopoietic Stem Cell Transplantation for Mixed or Overlap Myelodysplastic/Myeloproliferative Disorders

Symeonidis

Chondropoulos²,

Verigou³

et al. 2022

Front. Oncol.

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“…In our cohort, only 22 patients (10%) underwent alloSCT, which is similar to previous reports [ 18 , 54 ], mainly because the majority of CMML patients are elderly and not eligible for alloSCT. However, the outcomes of our patients after alloSCT were slightly better than those of other studies [ 55 , 56 ]. Our patients achieved a 4-year OS of 61%, and many of our patients were long survivors despite a cumulative incidence of relapse at four years of 43.7%.…”

Section: Discussioncontrasting

confidence: 85%

“…In fact, six of our patients harbored FLT3 or IDH mutations, which are druggable, and after treatment with FLT3 and IDH inhibitors, some attained a long-lasting response. These findings indicate that novel targeted therapies are feasible in CMML and suggest that new drug combinations could induce quicker and deeper responses and thus improve alloSCT outcomes [ 26 , 55 ]. In this line, there are several targeted drugs on an early phase of development (preclinical models or clinical trials) being tested in myeloid pathology that could be of utility on CMML in a foreseeable future.…”

Section: Discussionmentioning

confidence: 99%

Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

Castaño-Díez

López‐Guerra

Bosch-Castañeda

et al. 2022

Cancers

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Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and clonal evolution into AML. The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Median OS was 34 months and varied according to age, cytogenetic risk, FAB, CPSS and CPSS-Mol categories, and number of gene mutations. Hypomethylating agents were administered to 37 patients, 18 of whom responded. Allogeneic stem cell transplantation (alloSCT) was performed in 22 patients. Two-year OS after alloSCT was 60.6%. Six patients received targeted therapy with IDH or FLT3 inhibitors, three of whom attained a long-lasting response. AML transformation occurred in 53 patients and the analysis of paired samples showed changes in gene mutation status. Our real-world data emphasize that the outcome of CMML patients is still unsatisfactory and alloSCT remains the only potentially curative treatment. However, targeted therapies show promise in patients with specific gene mutations. Complete molecular characterization can help to improve risk stratification, understand transformation, and personalize therapy.

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“…17,25,44,45 Of note, similar to our results, no somatic mutation was associated with a difference in OS, relapse, or NRM in other studies, despite these mutations being associated with high risk in the nontransplantation setting. 24,46,47 Transplantation was associated with mutation clearance, and our analyses suggest that the negative impact of pathogenic mutations can be overcome by allo-HSCT. In the research of Nicolaus et al, neither TET2, ASXL1, CBL, nor NRAS mutations significantly influenced OS.…”

Section: Discussionmentioning

confidence: 60%

“…Previous investigations indicate that the important parameters affecting the transplantation outcome of CMML patients, include pretransplant therapy, 15,24 mutational landscape, 17,25 cytogenetic, 12,17 disease status at allo-HSCT, 14,16 palpable splenomegaly, 13,20 blast before transplant, 15 time from diagnosis to allo-HSCT, 14,20,26 type of donor source, 16 cGVHD, 27 and hematopoietic cell transplantation-specific comorbidity index (HCT-CI). 11,20 The prognostics values of previously developed prognostic scoring systems (CPSS, MDAPS, CPSS-mol, GFM, and MMM) have been evaluated in several studies of CMML patients undergoing transplantation.…”

Section: Discussionmentioning

confidence: 99%

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients withCMML

Zhou,

Wang,

Yuan

et al. 2023

American J Hematol

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Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post‐transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0–1), intermediate risk (2, 3), and high risk (4–6) three groups and the 3‐year overall survival (OS) were 93.3% (95%CI, 61%–99%), 78.9% (95%CI, 60%–90%), and 51.6% (95%CI, 32%–68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776–0.902) and 0.749 (95% CI, 0.684–0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo‐HSCT.

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Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelomonocytic Leukemia: Clinical and Molecular Genetic Prognostic Factors in a Nordic Population

Cited by 9 publications

References 27 publications

Allogeneic Hematopoietic Stem Cell Transplantation for Mixed or Overlap Myelodysplastic/Myeloproliferative Disorders

Allogeneic Hematopoietic Stem Cell Transplantation for Mixed or Overlap Myelodysplastic/Myeloproliferative Disorders

Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients withCMML

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