Tag Archives: blast phase

New Model Can Assess Blast Phase Progression Risk in Myeloproliferative Neoplasms

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November 12, 2024

Author(s): Alexandra Gerlach, Associate Editor

Researchers from Germany developed a model that utilizes 12 genetic markers to accurately distinguish patients with varying myeloproliferative neoplasms (MPNs) including chronic myeloid leukemia (CML) and BCR::ABL1 negative MPNs polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET). Using the model, clinicians can more precisely characterize their disease and determine their risk of progression to blast phase (BP).

Red blood cells and DNA strand | Image Credit: © GustavsMD – stock.adobe.com

MPNs are clonal disorders of the blood cells and bone marrow characterized by abnormal hematopoietic proliferation, which have been differentiated into 8 subclasses by the World Health Organization. However, the 4 classical types are CML, PV, PMF, and ET, characterized by mutations in the JAK2, CALR, or MPL driver genes.1,2

Diagnosis of a specific MPN is based on their unique morphology; for example, PV is distinguished by a hypercellular bone marrow and elevated hemoglobin level, compared with ET, which is characterized by megakaryocytic proliferation and increased platelet counts. However, this approach fails to acknowledge overlaps, borderline findings, or potential transitions to other MPN subtypes. Patients with PV and patients with ET can progress to post-PV or post-ET myelofibrosis (MF), underscoring the genetic intricacy of these disorders. There is also the risk of progression to BP, also called leukemic transformation, in which the presence of circulating or bone marrow blasts is ≥20%.2-4

In the study, the researchers aimed to use genetic markers to more effectively stratify CML, PV, PMF, and ET, as well as characterize patients with progression to BP. They developed a machine-learning model based on 12 genetic markers observed in routine analysis to accurately classify MPN subtypes and provide useful prognostic information in a user-friendly decision tree format for clinicians. Using data from over 500 patients, they were able to genetically characterize 355 individuals with 1 of the 4 classic MPNs.1

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New Insights Emerge on Treatment Outcomes for Accelerated or Blast-Phase Myeloproliferative Neoplasms

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Tori Rodriguez, MA, LPC, AHC

In recent years, several new therapies approved by the US Food and Drug Administration for the treatment of acute myeloid leukemia (AML) have been used in the management of accelerated or blast-phase myeloproliferative neoplasms (MPN-AP/BP). However, due to a dearth of prospective data on the efficacy of these therapies in patients with MPN-AP/BP, there remains a lack of consensus regarding their use in this population.1

In a retrospective, multicenter cohort study published in Blood Advances, researchers aimed to address this gap by investigating outcomes among 202 patients with MPN-AP/BP who were diagnosed and treated in the current era of myeloid therapies.1

Study Findings

The results demonstrated a median overall survival (OS) of 0.86 years, with no significant differences observed by first-line treatment type. The most common frontline strategies were intensive chemotherapy, DNA methyltransferase inhibitor (DNMTi)-based regimens, and DNMTi plus venetoclax–based regimens.1

An analysis of 65 patients who went on to receive allogeneic hematopoietic stem cell transplant (allo-HSCT) revealed a median OS of 2.30 years from the time of transplant.

In an interview with Hematology Advisor, study co-author Evan Chen, MD, a medical oncologist at Dana-Farber Cancer Institute and instructor in medicine at Harvard Medical School in Boston, Massachusetts, described 2 main takeaways from the findings: “First, outcomes of patients with MPN-AP/BP remain poor despite intensive chemotherapy and more recently developed, less-intensive venetoclax-based combinations. Second, a bone marrow transplant remains necessary for the possibility of long-term survival in the current treatment era for these patients.”

Despite the poor outcomes observed in this patient population, the present study found that “only 14% of patients were enrolled in clinical trials, and the criteria for assessing response in these patients is heterogeneous,” noted American Society of Hematology (ASH) media expert Ruben A. Mesa, MD, president and executive director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center in Winston-Salem, North Carolina.

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Retrospective Study Shows HSCT Consolidation After Blast Reduction Improves OS in Chronic Phase–Reverted MPN

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Ashling Wahner

Patients with myeloproliferative neoplasms in accelerated or blast phase (MPN-AP/BP) who revert to chronic phase (cMPN) after blast-reduction therapy, as well as those with complete response (CR) or CR with incomplete hematologic recovery (CRi) after blast reduction, experience improved overall survival (OS) outcomes after hematopoietic stem cell transplant (HSCT) consolidation therapy, according to findings from a single-center, retrospective analysis evaluating outcomes with intensive and nonintensive blast-reduction strategies in patients with MPN-AP/BP, which were published in Blood Advances.1

This study, which used clinically relatable response criteria developed at the Princess Margaret Cancer Centre, as well as the European LeukemiaNet (ELN) 2022 acute myeloid leukemia (AML) response criteria, found that patients who received intensive blast-reduction therapy achieved a best overall response rate (ORR) of 77% (n = 62/81) vs 39% (n = 21/54) in those who received nonintensive therapy. CR/CRi and cMPN reversions were observed in 24 and 38 patients in the intensive group and 4 and 17 patients in the nonintensive group, respectively.

Although allogeneic HSCT is the only therapy associated with long-term survival improvements for patients with MPN-AP/BP, this treatment strategy is typically reserved for patients who have achieved disease control. Other blast-reduction strategies include induction chemotherapy, as well as hypomethylating agents (HMAs)—such as azacitidine (Vidaza)—as monotherapy or in combination with agents such as venetoclax (Venclexta).2

“However, the optimal blast-reduction strategy and depth of disease clearance required before HSCT are unknown,” lead study author Marta B. Davidson, MD, PhD, FRCPC, of the Princess Margaret Cancer Centre in Toronto, Ontario, Canada, and coauthors, wrote in the paper.1 “Moreover, a lack of standardized response criteria to evaluate the treatment of MPN-AP/BP poses challenges for understanding treatment efficacy between reported studies.”

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