Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: CD8 DLI for Patients With Relapse or Residual Disease Following Allogeneic Stem Cell Transplantation

Summary: Primary Objectives:
  To evaluate response rates of acute or chronic Graft-versus-host disease (GVHD) following CD8 depleted DLI (Depleted Donor Lymphocyte Infusions) in patients with Chronic myelomonocytic leukemia (CMML), chronic lymphoid leukemia (CLL), Non-Hodgkin's lymphoma (NLM), Multiple Myeloma (MM) and Hodgkin's Lymphoma (HD).
  Secondary Objectives:
  -  To evaluate safety and treatment related mortality after CD8 depleted DLI.
  -  To evaluate the time to onset of GVHD following DLI and response to GVHD treatment.
  -  To evaluate the incidence and timing of pancytopenia following DLI.
  -  To evaluate disease-free survival, overall survival and relapse rates in three cohorts of patients; early relapse CML, late relapse CML and lymphoproliferative disorders (HD, CLL, NHL and MM).
  -  To evaluate the need and efficacy of second or subsequent CD8 depleted donor lymphocyte infusions.
  -  To evaluate the number of apheresis procedures needed to collect appropriate doses of CD4+ cells.


Eligibility: -  Patients of any age who have previously undergone allogeneic hematopoietic transplantation and have evidence of donor cell engraftment (>20% donor cell within three months of study entry)
  -  Expected survival >4 weeks
  -  CML patients with molecular, cytogenetic or hematologic relapse following allogeneic transplantation
  1. Molecular relapse- patients are eligible if bcr/abl is detectable at any time after day 180 post-allogeneic transplantation or if a negative bcr/abl PCR test was documented post-transplantation and the bcr/abl test is now positive by consecutive PCR determinations at least 4 weeks apart.
  2. Cytogenetic relapse-patients are eligible if standard cytogenetics demonstrate >10% t (9,22) positive cells greater than 60 days after myeloablative transplantation or 10% t (9,22) positive cells greater than 100 days after nonmyeloablative transplantation.
  -  CML patients with accelerated phase or blast crisis following allogeneic transplantation
  -  Patients with CLL, NHL, MM, or HD who have evidence of disease relapse or persistent disease at 60 days post-allo BMT and/or:
  1. MM- patients with a rising M-protein is detectable at 180 days post-transplant
  2. NHL - patients with molecular evidence of disease (bcl-2, t (4,11), etc.) at 180 days post transplant
  3. CLL, NHL or HD - patients with clear cut evidence of tumor growth at any time post-transplant are eligible
  -  Patients undergoing an HLA -identical or 5/6 antigen match transplant from a related or unrelated donor
  -  Patient's original donor must be available for lymphocyte donation
  -  There must be no evidence of active acute or graft-versus-host disease and patients should be off all immunosuppressive agents for, at least, two weeks prior to DLI. Patients on stable dose of methylprednisolone (<16 mg/d) without evidence of active GVHD are also eligible.
  -  Patients must have a Zubrod PS<2 (see appendix 7), Cr<2.5, bilirubin <3, and transaminases (SGPT, SGOT) <4x normal
  -  Patient must be able to sign informed consent

Relevance to patient case: not relevant