ASH 2011: Major Advances in Allogeneic Stem Cell Transplant Offer New Hope For Patients with Hematologic Malignancies

By Koen van Besien, MD, PhD

Allogeneic transplant can be curative for patients with lymphoma and is often effective in difficult situations where other treatments have failed. Unfortunately very few of us have suitable sibling donors and in a multi-ethnic society such as the US, finding HLA-identical donors in the transplant registry can also represent a challenge.  Several studies presented at the Annual Society of Hematology meeting offer evidence of rapid progress and increased success in the field of mismatched transplantation.  Dr. Symons from John’s Hopkins used mismatched related donors  ( also called haplo-identical donors i.e relatives who are partially HLA-identical) and with a novel chemotherapy regimen and  GVHD prophylaxis reported a low risk for graft vs host disease and excellent outcomes in patients with very high risk disease. Using similar technology even better results were reported by Dr. Bashey from Atlanta. He reported that the outcomes of such haplo-transplant were similar to those of transplants from HLA-identical siblings.  We used a slightly different approach and combined a haplo-identical transplant with an umbilical cord blood graft. In this procedure, the umbilical cord blood graft tends to assure long term hematopoiesis and may provide a more robust immune system with very little chronic graft vs host disease. We presented data on 51 patients with hematologic malignancies and the group from NIH used a similar approach to treat 10 pts with aplastic anemia. Both groups showed excellent rates of recovery and a high percentage of patients achieving prolonged remissions.  Dr. van Rood showed that the choice of umbilical cord graft may minimize the risk for disease recurrence.  It is too early to know which of these approaches, haplo or haplo-cord transplantation will ultimately become widely accepted, but the field is moving rapidly and options for patients who lack a sibling donor are rapidly improving.

Allogeneic transplantation for Hodgkin’s lymphoma

Though most patients with Hodgkin’s Lymphoma (HL) are cured with their initial treatment, a small percentage of them fail to achieve remission or relapse after initial treatment. Such patients usually receive a salvage chemotherapy regimen followed by autologous stem cell transplantation. However, only half of those undergoing autologous transplant are cured, and that percentage is even lower for those with incomplete responses to salvage. Using an innovative approach, Continue reading “ASH 2011: Major Advances in Allogeneic Stem Cell Transplant Offer New Hope For Patients with Hematologic Malignancies”

PYRAMID: A Personalized Medicine Study in Lymphoma

Update: this study is closed to enrollment. 

Pyramid Trial Background

With increasing knowledge of cancer biology and availability of new drugs, it is expected that therapy will be increasingly tailored to individual patients’ tumor subtypes. Examples of this in breast cancer, colon cancer and CML have emerged over the past ten years. Often referred to as “personalized medicine” or “precision medicine”, this targeted approach to cancer therapy relies on translational research that defines a drug’s clinical activity in the context of the tumor’s cellular and genomic pathology.

Translational research has characterized the molecular basis of the clinical heterogeneity in various lymphomas, and many new agents are in development for lymphoma. Although the targeted development of these drugs in specific lymphoma patient subgroups could potentially speed their availability to the right patients, there are two major challenges to targeted trials in lymphoma. First, the empiric clinical research has led to highly active drug combinations that improve outcomes for many patients with lymphoma and in some specific types current therapy does in fact successfully treat a portion of the patients; leaving fewer patients with an unmet medical need to enter clinical trials. Second, it is a practical challenge to test and quickly identify specific lymphoma patient subgroups that can be enrolled in clinical trials of targeted drugs. Therefore a personalized study should ideally use a practical, rapid test to identify a lymphoma group that is not responsive to known treatment and test a therapy that targets an important pathway in those tumors.

Pyramid Trial Summary

The PYRAMID trial addresses both of these issues in order to test an investigational combination of R-CHOP with or without VELCADE, a known NFKB inhibitor, specifically in non-GCB lymphoma. Continue reading “PYRAMID: A Personalized Medicine Study in Lymphoma”

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