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Pilot Study of Unrelated Donor Hematopoietic Stem Cell Transplantation in Patients With Life Threatening Hemophagocytic Disorders

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified October 2003 by Office of Rare Diseases (ORD).
Recruitment status was:  Active, not recruiting
Information provided by:
Office of Rare Diseases (ORD) Identifier:
First received: July 5, 2000
Last updated: June 23, 2005
Last verified: October 2003

OBJECTIVES: I. Determine the efficacy of unrelated donor hematopoietic stem cell transplantation in the treatment of patients with life threatening hemophagocytic disorders.

II. Determine the rate of disease free survival, incidence of graft failure, and incidence of graft versus host disease in these patients after undergoing this treatment regimen.

Condition Intervention
Chediak-Higashi Syndrome
Graft Versus Host Disease
X-Linked Lymphoproliferative Syndrome
Familial Erythrophagocytic Lymphohistiocytosis
Hemophagocytic Lymphohistiocytosis
Virus-Associated Hemophagocytic Syndrome
Drug: anti-thymocyte globulin
Drug: busulfan
Drug: cyclophosphamide
Drug: cyclosporine
Drug: etoposide
Drug: filgrastim
Drug: methotrexate
Procedure: allogeneic hematopoietic stem cell transplantation

Study Type: Interventional
Study Design: Primary Purpose: Treatment

Resource links provided by NLM:

Further study details as provided by Office of Rare Diseases (ORD):

Estimated Enrollment: 40
Study Start Date: March 2000
Detailed Description:

PROTOCOL OUTLINE: Patients receive oral busulfan twice a day on days -9 to -6; cyclophosphamide IV over 1 hour on days -5 to -2; etoposide IV over 4 hours on days -5 to -3; and anti-thymocyte globulin IV twice a day on days -2 and -1 and days 1 and 2. Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. Filgrastim (G-CSF) is administered subcutaneously beginning on day 1 and continuing until blood counts recover. Patients receive graft versus host disease prophylaxis with methotrexate IV on days 1, 3, 6, and 11 and cyclosporine IV over 1-4 hours (orally once the patients resumes eating) every 12 hours (every 8 hours for pediatric patients) starting on or prior to day -3 and continuing up to 1 year.

Patients are followed at days 28 and 100, at 6 months and 1 year, and then annually for 5 years.


Ages Eligible for Study:   up to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


--Disease Characteristics--

Patients diagnosed with any of the following active but stable, or nonactive/quiescent, hemophagocytic disorders:

  • Hemophagocytic lymphohistiocytosis (HLH)
  • Fever greater than 38.5 degrees Celsius
  • Splenomegaly (greater than 3 cm below costal margin)
  • Hemophagocytosis in bone marrow or spleen or lymph nodes
  • Disease may be confirmed by positive family history
  • No evidence of malignancy
  • Hypertriglyceridemia and/or hypofibrinogenemia
  • Fasting triglycerides at least 2.0 mmol/L or at least 3 standard deviations above normal for age
  • Fibrinogen no greater than 1.5 g/L or no greater than 3 standard deviations above normal
  • Cytopenia (affecting at least 2 of 3 lineages in the peripheral blood)
  • Hemoglobin less than 9.0 g/L
  • Platelet count less than 100,000/mm3

X-linked lymphoproliferative disorder (XLP)

Two or more maternally related males manifesting at least one of the following XLP phenotypes:

  • Fulminant infectious mononucleosis
  • Dysgammaglobulinemia
  • Malignant lymphoma/lymphoproliferative disorder
  • Aplastic anemia
  • Lymphoid granulomatosis/vasculitis OR
  • A maternally related male in an established XLP kindred who has strong genetic (RFLP) linkage to the XLP locus

Chediak-Higashi syndrome

Partial oculocutaneous albinism (hair, skin, eyes)

Frequent bacterial infections

Large peroxidase positive granules in leukocytes of peripheral blood or bone marrow

Positive family history or parental consanguinity is supportive of the diagnosis

May not have entered accelerated phase as defined by any of the following:

  • Lymphadenopathy
  • Pancytopenia
  • Histiocytes with hemophagocytosis in bone marrow, lymph nodes, liver, or spleen

Viral associated hemophagocytic syndrome (VAHS)

Relapsed after prior therapy or supportive care

Diagnostic criteria as for HLH

No hemophagocytic disorders secondary to underlying malignancy

Patients 35 years of age and under must have a hematopoietic stem cell donor that is one of the following:

  • HLA A and B identical OR
  • Single HLA A or B serologic mismatch with DRB1 identity OR
  • HLA A or B serologic identity with a single DRB1 mismatch

Patients 36 to 55 years of age must have a hematopoietic stem cell donor that is one of the following:

  • HLA A and B and HLA DRB1 identical OR
  • Single HLA A or B serologic mismatch with DRB1 identity

Patients receiving umbilical cord blood must have an unrelated donor with no more than two antigen HLA A, B, or DRB1 mismatches

--Patient Characteristics--

Performance status: Karnofsky 70-100% OR Age less than 16 years: Lansky 50-100%

Life expectancy: Not severly limited by another disease

Hepatic: SGOT less than 3 times normal Bilirubin less than 2.5 mg/dL

Renal: Creatinine normal OR Creatinine clearance or glomerular filtration rate greater than 50% normal

Cardiovascular: If symptomatic, ventricular ejection fraction must be greater than 40% and must improve with exercise OR Shortening fraction normal on echocardiogram


  • If symptomatic, DLCO greater than 45% predicted (corrected for hemoglobin)
  • In children unable to perform pulmonary function testing, oxygen saturation must be greater than 95%

Other: HIV negative No significant active infections

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Please refer to this study by its identifier: NCT00006056

United States, Minnesota
Fairview University Medical Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Fairview University Medical Center
Study Chair: K. Scott Baker Fairview University Medical Center
  More Information Identifier: NCT00006056     History of Changes
Other Study ID Numbers: 199/15106
Study First Received: July 5, 2000
Last Updated: June 23, 2005

Keywords provided by Office of Rare Diseases (ORD):
familial erythrophagocytic lymphohistiocytosis
hemophagocytic lymphohistiocytosis
Chediak-Higashi syndrome
X-linked lymphoproliferative syndrome
disease-related problem/condition
genetic diseases and dysmorphic syndromes
graft versus host disease
hematologic disorders
immunologic disorders and infectious disorders
primary immunodeficiency disease
rare disease
virus-associated hemophagocytic syndrome

Additional relevant MeSH terms:
Graft vs Host Disease
Lymphohistiocytosis, Hemophagocytic
Chediak-Higashi Syndrome
Lymphoproliferative Disorders
Pathologic Processes
Immune System Diseases
Histiocytosis, Non-Langerhans-Cell
Lymphatic Diseases
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Immunologic Deficiency Syndromes
Immunoproliferative Disorders
Antilymphocyte Serum
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action processed this record on April 24, 2017