Study of the Incidence of Muco-cutaneous Graft Versus Host Disease among patients undergoing Allogeneic Hematopoietic Stem Cell Transplantation in an Indian setting

BACKGROUND : Allogeneic hematopoietic stem cell transplants are being increasingly performed for various indications. GVHD is the most common complication of hematopoietic stem cell transplantation. Skin is the organ affected most often by this process. OBJECTIVE : To determine the incidence of muco-cutaneous GVHD, describe the clinical presentations, establish the clinico-pathological correlation of acute cutaneous GVHD and analyze the risk factors for GVHD in India. METHODOLOGY : A single centre prospective longitudinal study was performed in Christian Medical College, Vellore with 102 patients from March, 2009 to July, 2010. All patients undergoing hematopoietic stem cell transplantation were screened and recruited into the study prior to the transplant, after obtaining a written informed consent and an assent form for children where applicable, which was approved by the institutional review board. All patients were examined by the principal investigator prior to the transplant and periodically thereafter, every week or month, as the patient followed up, or if any mucocutaneous symptom appeared. The presence and extent of skin rash and oral mucosal involvement was clinically assessed, photographs were taken and biopsies performed where indicated, to help confirm the diagnosis, with the patient’s consent. Routine investigations, including total count, differential count and liver function tests were done regularly. Demographic data was collected from the records, as was the pre-transplant diagnosis, donor related information, stem cell source and conditioning regimen. The calculated sample size was 92. All statistical analysis was performed using SPSS 11.0 for windows (SPSS Inc, Chicago, IL). Frequency and percentages were used to describe the distribution of categorical variables, median and ranges were used to describe continuous variable that were not normal distributed. Chi-square test was used to assess the association between categorical variables. Continuous variables were compared using "t" test. Weighted kappa statistic was used to assess agreement between clinical and histopathological grades of GVHD; squared weights were employed. The agreement was analyzed using R 2.8. 0 (“irr” library). Logistic regression was employed to estimate the adjusted odds ratios as measure of risk for GVHD against potential risk factors. A p-value of less than 0.05 was considered statistically significant. RESULTS : Out of a sample size of 102 patients, 95 were evaluated for acute GVHD and 61 for chronic GVHD. Median age was 20.5 years. Males comprised 65.7% of the patient population. The most common primary diagnosis was AML, followed by thalassemia. Donors were mostly siblings, 77.4%; and unrelated donors comprised 14.7%. HLA type was identical in 92% of related transplants. ABO blood group incompatibility was seen in 45.1%. Gender mismatch from a female donor to male recipient was 33.3%. Peripheral blood was the most common source of hematopoietic stem cells, in 69.6%. Myeloablative conditioning was given for 53.9% patients. Cyclosporine and Methotrexate combination was given as prophylaxis for 94.1% patients. The median time to engraftment of neutrophils was 16 days (range, 9 to 57) and platelets was 17 days (range, 8 to 61). Acute muco-cutaneous GVHD was seen in 26.3% and chronic in 24.6% patients. Median time to onset of acute GVHD was 32 days (range, 11 to 95) and chronic GVHD was 231 (range, 130 to 497). Incidence of GVHD was found to be 58.9% in our population. There was a negative clinico-pathological correlation in acute cutaneous GVHD. Most of the risk factors analyzed did not reach statistical significance due to the presence of a heterogeneous population with differing diagnoses. However, older patient and donor age, and PBSCT were found to be significant risk factors for acute GVHD and older donor age for chronic GVHD. CONCLUSION : The incidence of acute muco-cutaneous GVHD was 26.3%, most commonly a maculopapular rash occuring around 32 days (range, 11 to 95). The incidence of chronic muco-cutaneous GVHD was 24.6%, most commonly lichenoid GVHD occurring around day 231 (130-497). Quiescent chronic GVHD is the most common type. Clinical and biopsy grades had no correlation in acute cutaneous GVHD. Older patient and donor age and PBSCT were risk factors for acute GVHD and older donor age was a significant risk factor for chronic GVHD.