Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators' Expression

We propose a clinical trial to define clinical endpoints, including engraftment, 100-day survival and one year survival (Objective #1). We will characterize the incidence, prevalence and function of immune checkpoint regulators in patients' blood and bone marrow following transplantation (Objective #2). We will correlate these laboratory results with clinical outcomes and the incidence of GVHD. As an exploratory aim, in those patients experiencing GVHD and requiring treatment, we will define the frequency/expression of checkpoint regulator expression and correlate these results with the patient's response to GVHD therapy.

Inclusion criteria

• Age: less than 75 years
• The patient must be approved for transplant by the treating transplant physician. This includes completion of their pre-transplant workup, as directed by standard Dartmouth-Hitchcock Medical Center (DHMC) Standard Operating Procedure (SOP) (DHMC SOP - Pre-transplant Evaluation of allogeneic recipient (Appendix).
• The patient must have a disease (listed below) with treatment-responsiveness that the treating transplant physician believes will benefit from an allogeneic stem cell transplant. The diseases include:
• Acute leukemia - Acute Myeloid Leukemia, Acute Lymphocytic Leukemia
• Chronic leukemia - Chronic Myeloid Leukemia, Chronic Lymphocytic Leukemia
• Myelodysplasia
• Myeloproliferative disorder
• Myelofibrosis
• Lymphoma - Non-Hodgkin's Lymphoma or Hodgkin's disease
• Plasma cell disorder, including myeloma, Waldenstrom's Macroglobulinemia
• Donor availability- the patient must have an identified RELATED haplo-identical donor
• No Human Immunodeficiency Virus infection or active hepatitis B or C
• Eastern Cooperative Oncology Group performance status: 0-2
• Diffusing capacity of carbon monoxide (DLCO) greater than or equal to 40 % predicted
• Left ventricular ejection fraction greater than or equal to 40%
• Serum bilirubin < 2x upper limit of normal; transaminases < 3x normal at the time of transplant
• No active or uncontrollable infection
• In female, a negative pregnancy test if experiencing menstrual periods
• No major organ dysfunction precluding transplantation
• No evidence of an active malignancy that would limit the patient's survival to less than 2 years. (If there is any question, the PI can make a decision).

Exclusion criteria

• Psychiatric disorder or a mental deficiency of the patient that is sufficiently severe to make compliance with the treatment unlikely, and making informed consent impossible.
• Major anticipated illness or organ failure incompatible with survival from bone marrow transplant.
• History of refractory systemic infection

DONOR ELIGIBILITY

• Human leukocyte antigen (HLA) haplo-identical matched related.
• The donor must be healthy and must be willing to serve as a donor, based on standard National Marrow Donor Program (NMDP) guidelines and DHMC SOP - Donor Evaluation (Appendix)
• The donor must have no significant co-morbidities that would put the donor at marked increased risk
• There is no age restriction for the donor
• Informed consent must be signed by donor

DONOR EXCLUSION CRITERIA

• The NMDP guidelines for exclusion criteria will be used (Appendix). In addition, the following donors are NOT eligible:
• Pregnant or lactating donor
• HIV or active Hep B or C in the donor
• Donor unfit to receive G-CSF and undergo apheresis
• A donor with a psychiatric disorder or mental deficiency that makes compliance with the procedure unlikely and informed consent impossible