Clonal hematopoiesis in patients with multiple myeloma undergoing autologous stem cell transplantation

Chitre, Sneha; Stölzel, Friedrich; Cuthill, Kirsty; Streetly, Mathew; Graham, Charlotte; Dill, Claudia; Mohamedali, Azim; Smith, Alexander E.; Schetelig, Johannes; Altmann, Heidi; Bornhäuser, Martin; Mufti, Ghulam J.

doi:10.1038/s41375-018-0208-8

Cited by 27 publications

(20 citation statements)

References 14 publications

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“…3b). We also observed a 136 (22) 271 (43) 358 (57) 493 78136 (22) 271 (43) 358 (57) worse OS and PFS in patients carrying more than one mutation ( Supplementary Fig. 5).…”

Section: Risk Of Tmnmentioning

confidence: 57%

“…Multiple reports have also demonstrated that CHIP is detectable in up to 30% of patients with non-Hodgkin lymphoma (NHL) at the time of ASCT and is associated with increased risk of TMN and non-relapse mortality [19][20][21] . The presence of CHIP has been reported in patients with MM, but that study was not powered to assess a relationship between CHIP and clinical outcomes 22 .…”

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confidence: 99%

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Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

et al. 2020

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Multiple myeloma (MM) is a plasma-cell neoplasm that is treated with high-dose chemotherapy, autologous stem cell transplant (ASCT) and long-term immunomodulatory drug (IMiD) maintenance. The presence of somatic mutations in the peripheral blood is termed clonal hematopoiesis of indeterminate potential (CHIP) and is associated with adverse outcomes. Targeted sequencing of the stem cell product from 629 MM patients treated by ASCT at the Dana-Farber Cancer Institute (2003-2011) detects CHIP in 136/629 patients (21.6%). The most commonly mutated genes are DNMT3A, TET2, TP53, ASXL1 and PPM1D. Twenty-one from fifty-six patients (3.3%) receiving first-line IMiD maintenance develop a therapy-related myeloid neoplasm (TMN). However, regardless of CHIP status, the use of IMiD maintenance associates with improved PFS and OS. In those not receiving IMiD maintenance, CHIP is associated with decreased overall survival (OS) (HR:1.34, p = 0.02) and progression free survival (PFS) (HR:1.45, p < 0.001) due to an increase in MM progression.

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“…3b). We also observed a 136 (22) 271 (43) 358 (57) 493 78136 (22) 271 (43) 358 (57) worse OS and PFS in patients carrying more than one mutation ( Supplementary Fig. 5).…”

Section: Risk Of Tmnmentioning

confidence: 57%

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confidence: 99%

Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

et al. 2020

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“…Somatic mutations associated with myeloid malignancies (≥2% VAF) can be detected in 5-30% of specimen from unselected, heavily pretreated patients undergoing autologous transplantation [77][78][79][80]. Again, the frequency of CH also depends on the sensitivity of the applied method.…”

Section: Clonal Hematopoiesis and Autologous Hematopoietic Cell Transplantationmentioning

confidence: 99%

Clonal hematopoiesis and its emerging effects on cellular therapies

et al. 2021

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The accumulation of somatic mutations in hematopoietic stem cells during aging, leading to clonal expansion, is linked to a higher risk of cardiovascular mortality and hematologic malignancies. Clinically, clonal hematopoiesis is associated with a pro-inflammatory phenotype of hematopoietic cells and their progeny, inflammatory conditions and a poor outcome for patients with hematologic neoplasms and solid tumors. Here, we review the relevance and complications of clonal hematopoiesis for the treatment of hematologic malignancies with cell therapeutic approaches. In autologous and allogeneic hematopoietic stem cell transplantation native hematopoietic and immune effector cells of clonal origin are transferred, which may affect outcome of the procedure. In chimeric antigen receptor modified T-cell therapy, the effectiveness may be altered by preexisting somatic mutations in genetically modified effector cells or by unmodified bystander cells harboring clonal hematopoiesis. Registry studies and carefully designed prospective trials will be required to assess the relative roles of donor- and recipient-derived individual clonal events for autologous and allogeneic cell therapies and to incorporate novel insights into therapeutic strategies.

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“…In another series, CH was identified in 18 of 161 leukapheresis samples (11%) from MM patients undergoing autologous transplant. 81 This might point toward a lower incidence of CH in myeloma as compared to NHL patients, possibly related to differences in pretransplant chemotherapy.…”

Section: Ch and Risk Of Therapy-related Myeloid Malignanciesmentioning

confidence: 99%

Clonal hematopoiesis and preleukemia—Genetics, biology, and clinical implications

Hartmann

Metzeler

2019

Genes Chromosomes & Cancer

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Myeloid neoplasms including myelodysplastic syndromes and acute myeloid leukemia (AML) originate from hematopoietic stem cells through sequential acquisition of genetic and epigenetic alterations that ultimately cause the disease‐specific phenotype of impaired differentiation and increased proliferation. It has become clear that preleukemic clonal hematopoiesis (CH), characterized by an expansion of stem and progenitor cells that carry somatic mutations but are still capable of normal differentiation, can precede the development of clinically overt myeloid neoplasia by many years. CH commonly develops in the aging hematopoietic system, yet progression to myelodysplasia or AML is rare. The discovery that myeloid neoplasms frequently develop from premalignant precursor conditions that are detectable in many healthy individuals has important consequences for the diagnosis, and potentially for the treatment of these disorders. In this review, we summarize the current knowledge on CH as a precursor of myeloid cancers and the implications of CH‐related gene mutations in the diagnostic workup of patients with suspected myelodysplastic syndrome. We will discuss the risk of progression associated with CH in healthy persons and in patients undergoing chemotherapy for a non‐hematologic cancer, and the significance of CH in autologous and allogeneic stem cell transplantation. Finally, we will review the significance of preleukemic clones in AML and their persistence in patients who achieve a remission after chemotherapeutic treatment.

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Clonal hematopoiesis in patients with multiple myeloma undergoing autologous stem cell transplantation

Cited by 27 publications

References 14 publications

Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

Clonal hematopoiesis is associated with adverse outcomes in multiple myeloma patients undergoing transplant

Clonal hematopoiesis and its emerging effects on cellular therapies

Clonal hematopoiesis and preleukemia—Genetics, biology, and clinical implications

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