Impact of donor-derived CD34 + infused cell dose on outcomes of patients undergoing allo-HCT following reduced intensity regimen for myelofibrosis: a study from the Chronic Malignancies Working Party of the EBMT

Czerw, Tomasz; Iacobelli, Simona; Malpassuti, Vittoria; Köster, Linda; Robin, Marie; Maertens, Johan; Chevallier, Patrice; Watz, Emma; Poiré, Xavier; Snowden, John A.; Kuball, Jürgen; Kinsella, Francesca; Blaise, Didier; Reményi, Péter; Méar, Jean-Baptiste; Cammenga, Jörg; Rubio, Marie Thérèse; Maury, Sébastien; Finnegan, Damian; Hayden, Patrick; Hernández‐Boluda, Juan Carlos; McLornan, Donal; Yakoub‐Agha, Ibrahim

doi:10.1038/s41409-021-01540-2

Cited by 9 publications

(9 citation statements)

References 35 publications

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“…Ruxolitinib therapy before HCT did not significantly impact on neutrophil engraftment in our cohort (p=0.27). CD34+ cell dose significantly influenced neutrophil engraftment with a median of 18 days if >8x10 6 cells/kg were infused versus 20 days with low cell numbers <6x10 6 cells/kg (p=0.037) consistent with effects observed in similar cohorts ( 31 , 32 ). We explored a potential impact of conditioning schemes used as preparatory regimens for allogeneic HCT in MF.…”

Section: Resultssupporting

confidence: 69%

Characterization of engraftment dynamics in myelofibrosis after allogeneic hematopoietic cell transplantation including novel conditioning schemes

et al. 2023

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IntroductionMyelofibrosis (MF) is a rare hematopoietic stem cell disorder progressing to bone marrow (BM) failure or blast phase. Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative therapy for a limited subset of patients with advanced MF, who are eligible, but engraftment in MF vs. AML is delayed which promotes complications. As determinants of engraftment in MF are incompletely characterized, we studied engraftment dynamics at our center.MethodsA longitudinal cohort of 71 allogeneic HCT performed 2000–2019 with >50% after 2015 was evaluated.ResultsMedian time to neutrophil engraftment ≥0.5x109/l was +20 days post-transplant and associated with BM fibrosis, splenomegaly and infused CD34+ cell number. Engraftment dynamics were similar in primary vs. secondary MF and were independent of MF driver mutations in JAK2, CALR and MPL. Neutrophil engraftment occurred later upon haploidentical HCT with thiotepa-busulfan-fludarabine conditioning, post-transplant cyclophosphamide and G-CSF (TBF-PTCy/G-CSF) administered to 9.9% and 15.6% of patients in 2000-2019 and after 2015, respectively. Engraftment of platelets was similarly delayed, while reconstitution of reticulocytes was not affected.ConclusionsSince MF is a rare hematologic malignancy, this data from a large number of HCT for MF is essential to substantiate that later neutrophil and platelet engraftment in MF relates both to host and treatment-related factors. Observations from this longitudinal cohort support that novel conditioning schemes administered also to rare entities such as MF, require detailed evaluation in larger, multi-center cohorts to assess also indicators of long-term graft function and overall outcome in patients with this infrequent hematopoietic neoplasm undergoing allogeneic transplantation.

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Section: Resultssupporting

confidence: 69%

Characterization of engraftment dynamics in myelofibrosis after allogeneic hematopoietic cell transplantation including novel conditioning schemes

et al. 2023

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“…A recent EBMT retrospective analysis reported improved rates of neutrophil and platelet engraftment in patients receiving a CD34+ cell dose of >7.0 Â 10 6 /kg, 88 with no evidence of adverse consequences from the higher dose. Of note, the presence of splenomegaly ≥5 cm compared to no splenomegaly or splenectomy remained a significant predictor of engraftment by multivariate analysis.…”

Section: Role Of Cd34+ Cell Dosementioning

confidence: 99%

Innovative strategies to improve hematopoietic stem cell transplant outcomes in myelofibrosis

et al. 2022

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Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by inflammation, marrow fibrosis, and an inherent risk of blastic transformation. Hematopoietic allogeneic stem cell transplant is the only potentially curative therapy for this disease, however, survival gains observed for other transplant indications over the past two decades have not been realized for MF. The role of transplantation may also evolve with the use of novel targeted agents. The chronic inflammatory state associated with MF necessitates pretransplantation assessment of end-organ function. Applying the transplant methodology employed for other myeloid disorders to patients with MF fails to acknowledge differences in the underlying disease pathophysiology. Limited understanding of the causes of poor transplant outcomes in this cohort has prevented refinement of transplant eligibility criteria in MF. There is increasing evidence of heterogeneity in molecular disease grade, beyond the clinical manifestations which have traditionally guided transplant timing. Exploring the physiological consequences of disease chronicity unique to MF, acknowledging the heterogeneity in disease grade, and using advanced prognostic models, molecular diagnostics and other organ function diagnostic tools, we present an innovative review of strategies with the potential to improve transplant outcomes in this disease. Larger, prospective studies which consider the impact of molecular-based disease grade are needed for MF transplantation.

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“…One recent EBMT study demonstrated that CD34+ stem cell doses of >7 × 10 6 / kg in matched sibling donor allo-HSCT associated with improved survival end-points and platelet engraftment. 74…”

Section: Stem Cell Source/dosementioning

confidence: 99%

“…Stem cell source is normally PB rather than BM, although large comparative studies are lacking. One recent EBMT study demonstrated that CD34+ stem cell doses of >7 × 10 6 /kg in matched sibling donor allo‐HSCT associated with improved survival end‐points and platelet engraftment 74 …”

Section: Special Situationsmentioning

confidence: 99%

The management of myelofibrosis: A British Society for Haematology Guideline

McLornan,

Psaila,

Ewing

et al. 2023

Br J Haematol

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This document represents an update of the British Society for Haematology guideline on Myelofibrosis first published in 2012 and updated in 2015. 1 These guidelines aim to provide healthcare professionals with clear guidance on stratified management for primary myelofibrosis (PMF), as well as postpolycythaemia myelofibrosis (post-PV MF) and postessential thrombocythaemia myelofibrosis (post-ET MF). A separate BSH guideline covers the diagnosis and prognostic evaluation of myelofibrosis and is published alongside this guideline. I N TRODUC T IONMyelofibrosis (MF) encompasses primary myelofibrosis (PMF), postessential thrombocythaemia (ET) MF and

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Impact of donor-derived CD34 + infused cell dose on outcomes of patients undergoing allo-HCT following reduced intensity regimen for myelofibrosis: a study from the Chronic Malignancies Working Party of the EBMT

Cited by 9 publications

References 35 publications

Characterization of engraftment dynamics in myelofibrosis after allogeneic hematopoietic cell transplantation including novel conditioning schemes

Characterization of engraftment dynamics in myelofibrosis after allogeneic hematopoietic cell transplantation including novel conditioning schemes

Innovative strategies to improve hematopoietic stem cell transplant outcomes in myelofibrosis

The management of myelofibrosis: A British Society for Haematology Guideline

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