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Alert Number 112

GVHD in Allo Stem Cell Transplants

Date: July 29, 2005

Graft-versus-host-disease (GVHD) is an example of systemic and potentially life threatening inflammation. It is one of the major causes of death in stem cell transplants. Controlling GVHD is the holy grail of all transplant researchers. The latest article on our website discusses the causes GVHD, and some commonsense things you can do to protect yourself. Even if you are not in the market for a stem cell transplant, controlling systemic inflammation is important for all CLL patients. As pointed out by Dr. Kanti Rai, inflammation of the lungs and resulting pneumonia is the cause of the hospitalization in a whopping 75% of CLL patients. You can read our review of Dr. Rai’s pivotal paper by clicking on the links below:

Role of Pulmonary Inflammation;
Chronic Inflammation and What You Can Do about It;

There is another similarity between GVHD and general CLL patients. TNF-alpha is a prognostic indicator in CLL patients, and reducing the levels of this potent inflammatory cytokine may be important in controlling the disease (see the abstract below, from M. D. Anderson). Did you know that the infamous “B-symptoms” (night sweats, weight loss etc) are driven by TNF-alpha? Well, this same TNF-alpha is also the culprit in GVHD, precipitating inflammatory over-kill. Other diseases where TNF-alpha is implicated are Ulcerative Colitis and Crohn’s disease (also called inflammatory bowel disease (IBD), where the mucosal lining of the GI tract is breached due to an out-of-control immune system attack. Many CLL patients are also cursed with IBD, you can see the common theme in all of this.

We suggest several common sense and practical things you can do to protect your mucosal linings. These are easy things to do, good things to discuss with your doctor, and they may well save you a whole lot of pain and suffering.

Be well,



Blood. 2002 Aug 15;100(4):1215-9.

The clinical significance of tumor necrosis factor-alpha plasma level in patients having chronic lymphocytic leukemia.

Ferrajoli A, Keating MJ, Manshouri T, Giles FJ, Dey A, Estrov Z, Koller CA, Kurzrock R, Thomas DA, Faderl S, Lerner S, O'Brien S, Albitar M.

Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston TX

Tumor necrosis factor-alpha (TNF-alpha), a cytokine possessing pleiotropic biological activities, is produced by leukemic lymphocytes in patients with chronic lymphocytic leukemia (CLL) and acts as an autocrine and paracrine growth factor in this disease. In this study, TNF-alpha levels were determined in 150 patients with CLL and correlated with disease characteristics, prognostic factors, and survival. The mean TNF-alpha plasma concentration in the patients with CLL was significantly higher than in the healthy control population (16.4 versus 8.7 pg/mL; P <.0001). Patients having an elevated TNF-alpha level had more advanced Rai and Binet stage disease, higher serum beta(2)-microglobulin (beta(2)M) levels, a greater percentage of cells expressing CD38, and lower hemoglobin and platelet levels. Patients having chromosomal abnormalities such as 11q deletion, trisomy 12, and chromosome 17 aberrations had a higher mean TNF-alpha level (27.5 pg/mL) than patients having a diploid karyotype or other miscellaneous cytogenetic abnormalities (14.2 pg/mL; P <.001). The TNF-alpha level was a predictor of survival when the Cox proportional hazards model was used with TNF-alpha entered as a continuous variable (P =.0001). Also, patients having a TNF-alpha level above the mean value of 14 pg/mL had significantly shorter survival duration (P =.00001). The TNF-alpha level remained predictive of survival in Cox multivariate analysis independent of Rai staging and beta(2)M, hemoglobin, prior therapy, white cell count, and platelet level (P =.005). We conclude that the TNF-alpha level serves as a prognostic factor in patients with CLL and that inhibition of TF-alpha in these patients could have therapeutic importance.

PMID: 1214920

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