Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor
- Malignant conditions for which CD34+ selected, T-cell depleted allogeneic
hematopoietic stem cell transplantation is indicated such as:
AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic
features (i.e. t 8;21, t15;17, inv 16).
- Secondary AML in 1st remission
- AML in 1st relapse or > 2nd remission
- ALL/LL in 1st remission clinical or molecular features indicating a high risk for
relapse; or ALL > 2nd remission
- CML failing to respond to or not tolerating Imatinib, dasatinib, or nilotinib in
first chronic phase of disease; or CML in accelerated phase or second chronic phase.
- Non-Hodgkins lymphoma with chemoresponsive disease in any of the following
categories: a) intermediate or high grade lymphomas who have failed to achieve a
first CR or have relapsed following a 1st remission who are not candidates for
- any NHL in remission which is considered not curable with chemotherapy alone and not
eligible/appropriate for autologous transplant. Myelodysplastic syndrome (MDS):
RA/RCMD with high risk cytogenetic features or transfusion dependence, RAEB-1 and
RAEB-2 and Acute myelogenous leukemia (AML) evolved from MDS, who are not eligible
for transplantation under protocol IRB 08-008.
- Chronic myelomonocytic leukemia: CMML-1 and CMML-2.
- Other rare lethal disorders of Hematopoiesis and Lymphopoiesis for which a T-cell
depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory
aplastic anemia or conjugated cytopenias; non-SCID lethal genetic immunodeficiencies
such as Wiskott Aldrich Syndrome, CD40 ligand deficiency, ALPS).
- Patients may be of either gender and of any racial or ethnic background.
- Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status >
- Patients must have adequate organ function measured by:
Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve
- Hepatic: < 3x ULN ALT and < 2.0x ULN total serum bilirubin, unless there is
congenital benign hyperbilirubinemia.
- Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal
range, then CrCl > 40 ml/min (measured or calculated/estimated)
- Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for
- Each patient must be willing to participate as a research subject and must sign an
informed consent form.
- Female patients who are pregnant or breast-feeding
- Uncontrolled viral, bacterial or fungal infection
- Patient seropositive for HIV-I/II; HTLV -I/II
- Presence of leukemia in the CNS.
- Two donors will be required for each transplant. Each HLA -A, B, C, DR, DQ
genotypically haplotype disparate related donor, should inherit one of the two HLA
haplotypes inherited by the patient. The second related donor should inherit the
patient's other HLA haplotype.
- Each donor must meet criteria outlined in the FACT-approved SOP for "DONOR EVALUATION
AND SELECTION FOR ALLOGENEIC TRANSPLANTATION" in the Blood and Marrow Transplant
Program Manual, document E-1 (see attached, or link to URL:
- Donor must have adequate peripheral venous catheter access for leukapheresis or must
agree to placement of a central catheter.
- Wt >25kg
Donor Exclusion Criteria:
- Evidence of active infection (including urinary tract infection, or upper respiratory
tract infection), viral hepatitis exposure (on screening), unless only HBS Ab+ and
HBV DNA negative, or serologic evidence of exposure or infection with HIV-I/II or
- Medical or physical reason which makes the donor unlikely to tolerate or cooperate
with growth factor therapy and leukapheresis
- Factors which place the donor at increased risk for complications from leukapheresis
or G-CSF therapy (e.g., autoimmune disease, sickle cell trait, symptomatic coronary
artery disease requiring therapy).
- Pregnancy (positive serum or urine β-HCG) or breastfeeding. Women of childbearing age
must avoid becoming pregnant while on the study