This is a single arm, open label, optimal 2-stage Simon design phase Ib-II clinical trial. Adult patients with hematological malignancies undergoing allogeneic HSCT from first- or second-degree haploidentical donor are eligible for the study if they meet the standard criteria defined in our institutional standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Patients will receive non-myeloablative, reduced-intensity or myeloablative conditioning regimen followed by peripheral blood hematopoietic stem cells. Patients will receive cyclophosphamide, abatacept, and short-duration tacrolimus for GvHD prophylaxis.

Inclusion Criteria:

1. Age ≥ 18 years
2. Karnofsky score ≥ 70%
3. No evidence of progressive bacterial, viral, or fungal infection
4. Creatinine clearance > 50 mL/min/1.72m2
5. Total bilirubin, ALT and AST < 2 x the upper limit of normal (except for diagnosed Gilbert's syndrome)
6. Alkaline phosphatase ≤ 250 IU/L
7. Left Ventricular Ejection Fraction (LVEF) > 45%
8. Adjusted Carbon Monoxide Diffusing Capacity (DLCO) > 60%
9. Negative HIV serology
10. Negative pregnancy test: confirmation per negative serum β-human chorionic gonadotropin (β-hCG) for women of childbearing age and potential.

Exclusion Criteria:

1. Donors are excluded in case of donor-specific HLA antibodies or positive cross-match.
2. Pregnant or nursing females or women of child bearing age or potential, who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from the first dose of conditioning regimen through day +180. A woman of reproductive capability is one who has not undergone a hysterectomy (removal of the womb), has not had both ovaries removed, or has not been post-menopausal (stopped menstrual periods) for more than 24 months in a row.
3. Male subjects who refuse to practice effective barrier contraception during the entire study treatment period and through a minimum of 90 days after the last dose of study drug, or completely abstain from heterosexual intercourse. This must be done even if they are surgically sterilized (i.e., post-vasectomy).
4. Inability to provide informed consent.
5. Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see Appendix E), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
6. Known allergies to any of the components of the investigational treatment regimen.
7. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
8. Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
9. Prisoners

The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: Maher.Abdulhay@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

beginning 9 months and ending 36 months following article publication

The investigator who proposed to use the data will be provided access upon reasonable request. Requests should be directed to Maher.Abdulhay@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

120 Days

Collected during study visits and interviews of a study participant presenting for medical care, or upon review by a study monitor.