Introduction: In this retrospective analysis, we provide a comprehensive account of the pathophysiology, clinical course and outcomes with various therapeutic regimens in HTLV-1 associated Adult T-cell Lymphoma/Leukemia- The Brooklyn Experience.
Patients and Methods:
We retrospectively reviewed the medical records of all patients identified as having acute type Human T-cell Lymphotropic Virus (HTLV-I) associated Adult T-cell Leukemia/Lymphoma (ATLL), from 1995 to 2005. The diagnosis was made according to REAL and WHO classification and based on clinical presentation, tissue biopsy and positive HTLV-I serology. Since all patients expired during the study, we used analysis of variance to examine the mean survival of these patients and the relationship between types of therapy and the survival.
We identified 44 patients with diagnosis of acute type ATLL. The most common disease presentation was lymphomatous in 70% (n=31) and leukemic presentation in 8% (n=3) both leukemia and lymphomatous presentation at diagnosis was seen in 22% (n=10) of patients. The mean survival for the entire group of patients was 31 weeks. The median survival was 16 weeks (range from 1 to 314 weeks). Patients who presented initially without hypercalcemia had a mean survival that was significantly higher than the patients with hypercalcemia 54 weeks versus 20 weeks, p<0.01. Treatment with infusional adriamycin chemotherapy significantly improved survival mean 99 ± 2.2 weeks, compared to CHOP 28 ± 2 weeks and much better than non-adriamycin regimens 21 ± 3 weeks p<0.001. Treatment with infusional adriamycin consistently improved survival in the patients without hypercalcemia 56± 6.6 weeks versus CHOP 21 ± 3.4 versus non-adriamycin containing regimens 10 ± 2.5 weeks, p=0.001. The presence or absence at diagnosis of central nervous system disease, pleural effusion, ascites, extensive liver or skin involvement or blood group were not independently associated with survival after adjusting for either hypercalcemia or infusional adriamycin chemotherapy. In multivariate analysis the presence of hypercalcemia was no longer significant after the therapy with infusional adriamycin.
Conclusions: Hypercalcemia portends poor prognosis in all forms of HTLV-1 associated ATLL and should be included in any risk stratification schema for this disease. Our review demonstrates a statistically significant improvement in median overall survival with infusional adriamycin based chemotherapy over traditional CHOP, CVP or the AZT and interferon combination. This superiority in outcomes was evident in patients with or without hypercalcemia at presentation. Although overall survival remains relatively low in the acute form of this disease and most patients remain incurable with current therapies, our findings suggest that the incorporation of infusional adriamycin based regimens in future treatment modalities to include specific and non-specific molecular targeted therapies, would be a prudent strategy in development of more effective therapies for this disease.