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Feasibility of Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation Followed by Donor Lymphocyte Infusions for Children at High Risk for Complications With Conventional Transplantation

21 Years
Not Enrolling
Leukemia, Lymphoma

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Trial Information

Feasibility of Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation Followed by Donor Lymphocyte Infusions for Children at High Risk for Complications With Conventional Transplantation


- Determine the feasibility of allogeneic hematopoietic stem cell transplantation using a
reduced-intensity conditioning regimen, in terms of whole blood engraftment rate at 100
days post transplant, in pediatric patients with hematopoietic malignancies who are at
high risk for complications with conventional transplantation.

- Determine the feasibility of donor lymphocyte infusions (DLIs), in terms of number of
patients who receive at least one DLI by 12 months post transplant, in patients treated
with this regimen.

- Determine the toxicities of the conditioning regimen, in terms of 100-day post
transplant nonrelapse-related death rate, in these patients.

- Determine the toxicity of DLI, in terms of acute and chronic graft-vs-host disease rate
and 12-month post transplant nonrelapse-related death rate, in these patients.

OUTLINE: This is a pilot study.

- Reduced-intensity conditioning regimen: Patients receive fludarabine IV on days -6 to
-2; antithymocyte globulin IV on days -5 to -2; and melphalan IV on days -3 and -2.

- Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation
on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 5 and continuing
until blood counts recover.

- Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV or orally
beginning on day -1 and continuing until at least day 28 and methotrexate IV on days 1,
3, and 6.

- Donor lymphocyte infusion (DLI): Patients with mixed chimerism, no acute GVHD requiring
therapy, and no relapse/progression post transplant at day 90 may receive DLI. At least
30 days after discontinuation of immunosuppression, patients may receive up to 2 DLIs
at least 8-12 weeks apart in the absence of GVHD.

At the completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Inclusion Criteria


- Diagnosis of one of the following hematopoietic malignancies:

- Acute lymphoblastic leukemia or myeloid leukemia with < 30% blasts in the bone

- Juvenile myelomonocytic leukemia

- Chronic myelogenous leukemia in chronic or accelerated phase

- Relapsed non-Hodgkin's or Hodgkin's lymphoma in at least partial remission

- Considered at high risk (> 30%) of toxic death with standard hematopoietic stem cell
transplantation (HSCT), as indicated by at least one of the following:

- Creatinine > 1.5 times normal OR creatinine clearance < 70 mL/min OR tubular
damage that is not corrected by cessation of chemotherapy

- DLCO < 60% of predicted OR history of prior intubation due to lung disease
(intubation for surgery excluded)

- Shortening fraction < 30%

- History of disseminated fungal infection during chemotherapy OR currently
receiving antifungal agents OR history of ≥ 2 septic episodes (confirmed by
cultures) that required ICU support

- Patients with improving fungal or other infections eligible

- Improving infection is defined as confirmed negative cultures on 2
separate occasions, at least 1 week apart, and/or stable or improving
imaging studies (e.g., CT scan) of the infected site

- Two imaging studies taken at least 2 weeks apart must show stable or
improved disease

- History of stroke or abnormal MRI/MRA OR leukoencephalopathy OR seizures that
are not fully controlled with anticonvulsants (> 2 episodes of seizures in the
preceding year or 1 episode of status epilepticus in a patient who is receiving
anticonvulsant therapy)

- History of prior significant bleeding (e.g., pulmonary, CNS, or
gastrointestinal) OR history of a clotting disorder as manifested by prior
significant thromboses (e.g., superior vena cava, inferior vena cava, or femoral

- Failed conventional therapies and not eligible for myeloablative protocols

- May have failed prior conventional HSCT

- No active CNS leukemia

- Unrelated or related donor available, meeting the following criteria:

- Matched for at least 7/8 loci by high-resolution typing

- One mismatch at A, B, or C loci allowed

- Fully matched at DRB1 locus


- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- No active/progressing viral, bacterial, protozoal, or fungal infection

- Transaminases ≤ 5 times normal (except in the presence of autoimmune liver disease)

- Shortening fraction ≥ 25%

- DLCO ≥ 40% OR pulse oximetry ≥ 85% on room air

- Glomerular filtration rate ≥ 40 mL/min


- See Disease Characteristics

- Prior prolonged intensive chemotherapy (> 3 years of therapy or ≥ 3 different
chemotherapeutic protocols) allowed

Type of Study:


Study Design:

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

Principal Investigator

Biljana Horn, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco


United States: Federal Government

Study ID:




Start Date:

January 2003

Completion Date:

January 2008

Related Keywords:

  • Leukemia
  • Lymphoma
  • childhood acute lymphoblastic leukemia in remission
  • childhood acute myeloid leukemia in remission
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • recurrent childhood small noncleaved cell lymphoma
  • juvenile myelomonocytic leukemia
  • chronic phase chronic myelogenous leukemia
  • accelerated phase chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • childhood chronic myelogenous leukemia
  • Leukemia
  • Lymphoma



UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115