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In-vivo T-cell Depletion and Hematopoietic Stem Cell Transplantation for Life-Threatening Immune Deficiencies and Histiocytic Disorders

Phase 2/Phase 3
55 Years
Open (Enrolling)
Hemophagocytic Lymphohistiocytosis, X-Linked Lymphoproliferative Disorders, Chediak-Higashi Syndrome, Griscelli Syndrome, Immunologic Diseases, Langerhans-Cell Histiocytosis, Hematologic Diseases

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Trial Information

In-vivo T-cell Depletion and Hematopoietic Stem Cell Transplantation for Life-Threatening Immune Deficiencies and Histiocytic Disorders

Subjects will begin chemotherapy as a preparative regimen, which is intended to completely
eliminate their defective immune system and bone marrow. The preparative regimen consists
of the chemotherapy drugs (busulfan, cyclophosphamide, and antithymocyte globulin (ATG)).

Transplantation: subjects will then have a source of blood stem cells (bone marrow) from
their donor administered into their catheter. Medication will be given to help prevent
Graft-Versus Host Disease (GVHD). The ATG will help to deplete the donor stem cells of the
type of cells that can cause GVHD and will also help to promote engraftment of the new stem

Recovery Phase: The second phase of treatment consists of a period after transplantation
during which we wait for the return of bone marrow function. This usually takes two to four
weeks. Subjects will be given a blood cell growth factor, G-CSF, to help speed recovery of
the white blood cells and potentially decrease the risk of infection and decrease the time
until the bone marrow recovers.

Inclusion Criteria:

- Any patient from birth to < 55 years of age fulfilling the following criteria will be
eligible for this study.

- Patients meeting clinical diagnostic criteria for Hemophagocytic Lymphohistiocytosis

- Patients meeting clinical diagnostic criteria or genetic diagnosis of X-linked
lymphoproliferative disorder (XLP) and whose disease is ACTIVE but STABLE, or

- Patients with Chediak-Higashi Syndrome who meet the following diagnostic criteria and
whose disease is ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT as defined in Appendix V
of the study protocol.

- Patients with Viral Associated Hemophagocytic Syndrome (VAHS) - if relapsed after
other therapy or supportive care. Diagnostic criteria as above for HLH. Disease
status must be ACTIVE but STABLE, or NON-ACTIVE/QUIESCENT as defined in Appendix V.
It is cautioned that many patients with HLH or familial hemophagocytic
lymphohistiocytosis (FHL) will have a viral infection at time of initial presentation
and may therefore be misdiagnosed as having VAHS.

- Griscelli Syndrome

- Primary immune deficiencies with non-genotypic identical donors only.

- Progressive Langerhans cell histiocytosis unresponsive to standard therapy.

- Other non-malignant hematological disorders in which stem cell transplant with a
myeloablative regimen is indicated.

- Diamond Blackfan Anemia if transfusion dependent

- Schwachman Diamond Syndrome: with cytopenias or transformation to myelodysplastic
syndrome (MDS)

- Kostman's Syndrome (if ANC <500 without GCSF support, or transformation to MDS)

- Congenital dyserythropoietic anemia if transfusion dependent

- Amegakaryocytic thrombocytopenia if baseline platelet counts <20,000 or requiring

- Cardiac, hepatic, renal and pulmonary function deemed adequate for high dose
chemotherapy with stem cell rescue as per institutional standards. General
guidelines are as follows:

- Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection
fraction at rest must be > 40% and must improve with exercise, or shortening
fraction by echocardiogram must be within institutional normals

- Hepatic: < 3 x normal SGOT and < 2.5 mg/dL serum bilirubin

- Renal: Serum creatinine within normal range, or if serum creatinine outside
normal range then creatinine clearance or glomerular filtration study should be
> 50% of normal.

- Pulmonary: Asymptomatic or, if symptomatic, diffusing capacity of the lung for
carbon monoxide (DLCO) > 45% of predicted (corrected for hemoglobin). For
children unable to perform pulmonary function testing, then oxygen saturation
should be >95%.

- Availability of a suitable allogeneic bone marrow donor as per current institutional
guidelines for non-T cell depleted hematopoietic stem cell transplant (HSCT).

- Patients who have undergone previous stem cell transplant (SCT) and failed
engraftment or who had relapse of their disease are considered eligible if they meet
other eligibility criteria and if the second SCT would occur 6 months or more after
the first. If the first SCT preparative regimen was of a non-myeloablative intensity
then the second SCT could be performed earlier when the acute toxicity from that
procedure was resolved.

Exclusion Criteria:

- Patients who are moribund or whose life expectancy is severely limited by disease
other than their underlying disorder. Karnofsky performance status < 70% or Lansky <
50% for patients < 16 years.

- Patients with hemophagocytic disorders secondary to underlying malignancy.

- Patients who have ACTIVE/UNSTABLE disease as defined in Appendix V.

- Significant active infections, including Human Immunodeficiency Virus (HIV).

- Age > 55 years.

- Not providing informed consent.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to transplant engraftment

Outcome Time Frame:

Day 100 Post Transplant

Safety Issue:


Principal Investigator

Angela Smith, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Minnesota Medical Center


United States: Institutional Review Board

Study ID:




Start Date:

September 2000

Completion Date:

July 2015

Related Keywords:

  • Hemophagocytic Lymphohistiocytosis
  • X-Linked Lymphoproliferative Disorders
  • Chediak-Higashi Syndrome
  • Griscelli Syndrome
  • Immunologic Diseases
  • Langerhans-Cell Histiocytosis
  • Hematologic Diseases
  • Stem Cell Transplant
  • T-cell depletion
  • immune deficiencies
  • Busulfan pharmacokinetics
  • Non-Malignant Hematological Disorders
  • Chediak-Higashi Syndrome
  • Hematologic Diseases
  • Histiocytosis
  • Histiocytosis, Langerhans-Cell
  • Immune System Diseases
  • Lymphohistiocytosis, Hemophagocytic
  • Lymphoproliferative Disorders



Masonic Cancer Center, University of Minnesota Minneapolis, Minnesota  55455