HLA-Mismatched Unrelated Donor Bone Marrow Transplantation With Post-Transplantation Cyclophosphamide

Inclusion Criteria:

1. Age ≥ 15 years and < 71 years at the time of signing the informed consent form

2. Partially HLA-mismatched unrelated donor: HLA typing will be performed at high
resolution (allele level) for the HLA-A, -B, -C, and -DRB1 loci; a minimum match of
4/8 at HLA-A, -B, -C, and -DRB1 is required

3. Product planned for infusion is bone marrow

4. Disease and disease status:

1. Acute Leukemias or T lymphoblastic lymphoma in 1st or subsequent complete
remission (CR): Acute lymphoblastic leukemia (ALL)/T lymphoblastic lymphoma;
acute myelogenous leukemia (AML); acute biphenotypic leukemia (ABL); acute
undifferentiated leukemia (AUL)

2. Myelodysplastic Syndrome (MDS), fulfilling the following criteria: Subjects with
de novo MDS who have or have previously had Intermediate-2 or High risk disease
as determined by the International Prognostic Scoring System (IPSS). Current
Intermediate-2 or High risk disease is not a requirement; Subjects must have <
20% bone marrow blasts, assessed within 60 days of informed consent; Subjects may
have received prior therapy for the treatment of MDS prior to enrollment

3. Chronic Lymphocytic Leukemia (CLL) in CR if RIC is to be used; in CR or partial
response (PR) if FIC is to be used

4. Chronic myeloid leukemia (CML) in 1st or subsequent chronic phase characterized
by <10% blasts in the blood or bone marrow.

5. Chemotherapy-sensitive lymphoma in status other than 1st CR

5. Performance status: Karnofsky or Lansky score ≥ 60% (Appendix A)

6. Adequate organ function defined as:

1. Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 35% (RIC cohort) or
LVEF at rest ≥ 40% (FIC cohort), or left ventricular shortening fraction (LVFS) ≥
25%

2. Pulmonary: diffusing capacity of the lungs for carbon monoxide (DLCO), forced
expiratory volume (FEV1), forced vital capacity (FVC) ≥ 50% predicted by
pulmonary function tests (PFTs)

3. Hepatic: total bilirubin ≤ 2.5 mg/dL, and alanine aminotransferase (ALT),
aspartate aminotransferase (AST), and alkaline phosphatase (ALP) < 5 x upper
limit of (ULN) (unless disease related)

4. Renal: serum creatinine (SCr) within normal range for age (see table 2.3). If SCr
is outside normal range for age, creatinine clearance (CrCl) > 40 mL/min/1.73m2
must be obtained (measured by 24-hour (hr) urine specimen or nuclear glomerular
filtration rate (GFR), or calculated GFR (by Cockcroft-Gault formula for those
aged ≥ 18 years; by Original Schwartz estimate for those < 18 years))

7. Subjects ≥ 18 years of age must have the ability to give informed consent according to
applicable regulatory and local institutional requirements. Legal guardian permission
must be obtained for subjects < 18 years of age. Pediatric subjects will be included
in age appropriate discussion in order to obtain assent.

8. Subjects with documentation of confirmed HIV-1 infection (i.e. HIV-positive), and a
hematologic malignancy who meets all other eligibility requirements must:

1. Receive only RIC regimen (i.e. Regimen A)

2. Be willing to comply with effective antiretroviral therapy (ARV)

3. Have achieved a sustained virologic response for 12 weeks after cessation of
hepatitis C antiviral treatment (in HIV-positive subjects with hepatitis C)

Exclusion Criteria:

1. HLA-matched related or 8/8 allele matched (HLA-A, -B, -C, -DRB1) unrelated donor
available. This exclusion does not apply to HIV-positive subjects who have a
CCR5delta32 homozygous donor.

2. Autologous HCT < 3 months prior to the time of signing the informed consent form

3. Females who are breast-feeding or pregnant

4. HIV-positive subjects:

1. Acquired immunodeficiency syndrome (AIDS) related syndromes or symptoms that may
pose an excessive risk for transplantation-related morbidity as determined by the
Treatment Review Committee (see Appendix D).

2. Untreatable HIV infection due to multidrug ARV resistance. Subjects with a
detectable or standard viral load > 750 copies/mL should be evaluated with an HIV
drug resistance test (HIV-1 genotype). The results should be included as part of
the ARV review (described in Appendix D).

3. May not be currently prescribed ritonavir, cobacistat and/or zidovudine

5. Current uncontrolled bacterial, viral or fungal infection (currently taking medication
with evidence of progression of clinical symptoms or radiologic findings)

6. Prior allogeneic HCT

7. History of primary idiopathic myelofibrosis

8. MDS subjects may not receive RIC and must be < 50 years of age at the time of signing
the informed consent form