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Protocol No. UW17025

Principal Investigator Hofmann, Inga

Phase II

Age Group Both

Scope National

Sponsor Type Institutional

Title Radiation- and alkylator-free hematopoietic cell transplantation for bone marrow failure due to dyskeratosis congenita / telomere disease.

Objective The purpose of this research study is to see whether using a low-intensity “conditioning regimen” (i.e. less chemotherapy/radiation/other drugs) to prepare for BMT for DC/TD will be effective, but with less side effects compared to the standard BMT treatments that are currently performed at our hospital and at other transplant centers. We hope that by reducing the side effects under this regimen, patients with DC/TD will be able to undergo BMT with better health and survival. Specifically, the research study is being done to answer the following questions:
  • Is a BMT with a less intense conditioning regimen effective in treating the blood problems in DC/TD?
  • After BMT with this less intense preparative regimen, will people with DC/TD experience fewer side effects that shorten their life or worsen their quality of life?

  • Treatment
    Conditioning, Bone marrow transplant/infusion of cells, Immunosuppression to prevent graft-versus-host disease

    Key Eligibility
  • Patients 30 days to 65 years of age at the time of registration with a diagnosis of severe aplastic anemia or single lineage cytopenia, defined as follows: Bone marrow hypocellular for age on biopsy based on review at the enrolling institution within 90 days of protocol registration,
  • One or more of the following (in peripheral blood):
  • neutrophils < 0.5 x 109/L
  • platelets < 30 x 109/L, or platelet transfusion dependence
  • reticulocytes < 50 x 109/L in anemic patients, or red cell transfusion dependence
  • transfusion dependence will be defined as greater than ONE transfusion of platelets or red blood cells in the last year prior to protocol registration
  • age-adjusted mean telomere length < 1%ile in peripheral blood lymphocytes by flow-FISH on any occasion, as reported by a CLIAapproved laboratory
  • pathogenic mutation(s) in DKC1,TERC, TERT, NOP10, NHP2, TCAB1, TINF2, CTC1, RTEL1, ACD, or PARN as reported by a CLIA-approved laboratory
  • Diagnosis with one of the following DC categories on any prior evaluation:
  • age-adjusted mean telomere length < 1%ile in peripheral blood lymphocytes by flow-FISH on any occasion, as reported by a CLIAapproved laboratory pathogenic mutation(s) in DKC1,TERC, TERT, NOP10, NHP2, TCAB1, TINF2, CTC1, RTEL1, ACD, or PARN as reported by a CLIA-approved laboratory
  • Dyskeratosis congenita diagnosed by:
  • clinical triad: abnormalities of skin pigmentation, nail dystrophy, oral leukoplakia OR
  • one of clinical triad and presence of two or more associated features: epiphora, developmental delay, mental retardation, pulmonary disease, short stature, dental caries/loss, esophageal stricture, grey hair, hyperhidrosis, malignancy, intrauterine growth retardation (IUGR), liver disease, enteropathy, ataxia/cerebellar hypoplasia, hypogonadism, microcephaly, urethral stricture, osteoporosis/AVN, scoliosis, deafness
  • Hoyeraal Hreidarsson syndrome: cerebellar hypoplasia, microcephaly, IUGR, “T+B-NK-“ immunodeficiency
  • Revesz syndrome: exudative retinopathy, cerebral calcifications, IUGR, fine sparse hair, ataxia
  • Availability of a HLA-compatible related or unrelated donor, defined as a 7/8 or 8/8 match for HLA-A, B, C, and DRB1. Related donors must be ruled out for telomere disease by appropriate clinical and diagnostic measures (for example, clinical evaluation, flow-FISH telomere length testing, genetic testing, and/or bone marrow examination)
  • Matched unrelated donor must consent to provide a bone marrow allograft
  • Adequate renal function with glomerular filtration rate
  • EXCLUSION:
  • Clonal cytogenetic abnormalities associated with MDS or AML on bone marrow examination
  • Karnofsky performance status < 40% for patients 16 years old or older; or Lansky < 40% for patients < 16 years old
  • Uncontrolled bacterial, viral or fungal infections
  • Positive for the human immunodeficiency virus (HIV) by nucleic acid testing
  • Pregnant or breastfeeding
  • Prior allogeneic marrow or stem cell transplantation
  • Prior solid organ transplantation

  • Applicable Disease Sites Hematologic cancers, other

    Status Open

    Participating Institutions UW Hospital and Clinics