Assessing Pyruvate Kinase Deficiency in Blood Disorders

Characterization Of Acquired Pyruvate Kinase Deficiency In Clonal Myeloid Neoplasms

This study is testing how common a specific enzyme deficiency is in people with certain blood disorders by taking a single blood sample from them.

Quick facts

• Study type: Observational
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (Academic / other)
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT04902833 on ClinicalTrials.gov

What this trial studies

This observational study aims to evaluate the prevalence of acquired pyruvate kinase deficiency in patients with specific blood disorders through a single blood draw. Participants will be divided into two cohorts: one consisting of anemic patients with myelodysplastic syndromes (MDS) and another with clonal myeloid disorders exhibiting unexplained hemolytic anemia. The study will analyze red cell pyruvate kinase enzyme activity and perform next-generation sequencing on blood samples to gather genomic evidence. Approximately 100 individuals will be recruited for this assessment.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with anemia related to myelodysplastic syndromes or clonal myeloid neoplasms.

Not a fit: Patients with anemia due to nutritional deficiencies or other non-clonal causes may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to better understanding and management of pyruvate kinase deficiency in patients with blood disorders.

How similar studies have performed: While this approach is focused on a specific deficiency in a defined patient population, similar studies have shown promise in understanding genetic contributions to blood disorders.

Eligibility criteria

Inclusion Criteria:

* Cohort 1

  * Capable and willing to provide informed consent for participation in the study.
  * Diagnosis of clonal cytopenia of undetermined significance (CCUS), myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN syndrome) according to 2016 World Health Organization (WHO) classification system.
  * Anemia secondary to underlying clonal cytopenia of undetermined significance (CCUS), MDS or MDS/MPN syndrome, defined as a hemoglobin \<11.0 g/dL measured within 30 days of study enrollment. Anemia should not be related to nutritional deficiency (such as iron, cobalamin, folate, or copper deficiencies), peripheral immune or non-immune hemolysis, or renal disease, in the opinion of the investigator.
  * Age \>18 years.
* Cohort 2

  * Capable and willing to provide informed consent for participation in the study.
  * Diagnosis of a clonal myeloid neoplasm, such as MDS, MDS/MPN syndrome, myeloproliferative neoplasm (MPN), acute myeloid leukemia (AML), clonal cytopenia of undetermined significance (CCUS), or other clonal myeloid neoplasm according to 2016 World Health Organization (WHO) classification system.
  * A diagnosis of an otherwise unexplained Coombs-negative non-immune hemolytic anemia, according to the clinical judgement of the investigator. Some form of objective laboratory evidence must be present, including one or more of the following: negative direct antiglobulin (Coombs) test, reduced haptoglobin, elevated indirect bilirubin, elevated lactate dehydrogenase, elevated aspartate aminotransferase, or compatible findings on peripheral blood film. Results of all of these tests are not required to satisfy this criterion.
  * Age \>18 years.

Exclusion Criteria:

* Cohort 1

  * Receipt of red cell transfusion within 60 days of study enrollment.
  * Have a known untreated nutritional anemia or acquired disorder resulting in hemolysis, such as paroxysmal nocturnal hemoglobinuria (PNH). A known hereditary anemia (such as thalassemia trait) is not exclusionary if the patient's baseline hemoglobin has worsened significantly (in the opinion of the investigator) after development and diagnosis of MDS.
* Cohort 2

  * Have a known hereditary anemic disorder, such as thalassemia, sickle cell disease, or hereditary enzyme deficiency, with the exception of hereditary X-linked glucose-6-phosphate dehydrogenase deficiency known not to cause chronic baseline hemolysis. Testing for these diagnoses is not required unless deemed clinically necessary.
  * Have a known untreated nutritional anemia or acquired disorder resulting in hemolysis, such as paroxysmal nocturnal hemoglobinuria (PNH).

Where this trial is running

Boston, Massachusetts

• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Hanny Al-Samkari, MD — Massachusetts General Hospital
• Study coordinator: Hanny Al-Samkari, MD

Conditions Pyruvate Kinase Deficiency; Pyruvate Kinase Deficiency Anemia; Hereditary Hemolytic Anemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm; Clonal Myeloid Neoplasm; Myeloproliferative Neoplasm; Acute Myeloid Leukemia