Thursday, July 7, 2011

CLL and stem cell transplants

Today in morning report, and interesting case of fever in CLL. Here is a link to a prior post on CLL and immunodeficiency; see the bottom of the post for a link to the role of IVIG:
The other discussion was on stem cell transplants and graft versus host disease (GVHD). A few points:

1) Types of stem cell transplant:
Autologous: Patient's own mononuclear cells are harvested from bone marrow or (now more commonly) from peripheral blood prior to high-dose myeloablative chemotherapy/radiotherapy. The cells are then reinfused during the period of prolonged bone marrow failure that occurs after these treatments in order to help restore hematopoiesis. Classically this type of transplant was used in lymphoma, but there is an ever-expanding list of trials for other indications including solid tumors and plasma-cell dyscrasias.

Allogeneic: Stem cells are harvested from the bone marrow of healthy donors or newborn umbilical cord/placenta. The cells are infused to reconstitute the patient's hematopoeitic system, but also can have direct anti-leukemia activity, termed graft-versus-leukemia (GVL). Given that the cells are from a donor, there are a greater number of risks than in autologous transplant due to immune suppression and graft-versus-host-disease (below).

2) Graft versus host disease:
Lymphocytes from the donor may target normal host tissues and cause inflammation, with particular predilection for skin, gut, liver, and lungs. The acute form usually occurs before 100 days post-transplant and can present with a maculopapular or bullous rash, cholestasis potentially leading to hepatic failure, or secretory diarrhea. The chronic form more resembles other autoimmune disorders, presenting with arthritis, scleroderma-like skin changes, sicca syndrome, chronic hepatitis, and GI malabsorbtion.

The risk of GVHD is directly related to age and inversely related to the the degree of major histocompatibility antigen matching between donor and recipient. It remains the major complication of allogeneic transplant, affecting upwards of 40% of patients.

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