Characteristics and Outcomes of Lymphoblastic Lymphoma Patients - the University of Miami Experience

BACKGROUND: Lymphoblastic lymphoma (LBL) is an uncommon adult malignancy accounting for <2% of non-Hodgkin´s lymphomas. This high-grade lymphoma is most commonly of T-cell immunophenotype and it is thought to be the nodal/extra nodal presentation of acute lymphoblastic leukemia (ALL). Arbitrarily, 25% bone marrow involvement has been considered cut-off in differentiating between LBL and ALL. The optimal standard treatment for adult with LBL is not yet defined due to rarity of the disease and absence of large randomized prospective studies. Therefore, current recommendation are based on ALL and pediatric population experience. Hyper-CVAD is one of the most commonly utilized regimens for this disease in US. The purpose of this study was to review our experience in LBL patients, most of whom received therapy with Hyper-CVAD regimen followed by POMP maintenance.

METHODS: Retrospective review of patients with LBL treated at University of Miami (UM) Health System from January 1995 to June 2015. HIV positive patients were excluded.

RESULTS: 32 patients were identified in review of clinical and pathological lymphoma databases. Patients with >25% bone marrow involvement or leukemic presentation in the peripheral blood were excluded. Median age at diagnosis was 34 years (range 17 to 76 years), 23 (72%) patients were male, 14 (44%) were Hispanics, and 30 (94%) had an ECOG performance status of 0-2, and 2 had ECOG of 3-4. 30 (94%) LBL tumors were of T cell origin. Bulky disease was present in 13(41%), mediastinal involvement in 23(72%), pleural/pericardial effusion in 19(59%), SVC syndrome in 6(19%), CNS disease at presentation in 4(12%), and bone marrow involvement (6 to 25%) in 10(31%) patients. 20(62%) patients presented with stage III/IV, 21(66%) with elevated LDH, 13(41%) with B symptoms and 15(47%) patients had high IPI. Median follow-up of all patients was 54 months (range 3.5 to 195months). 30 patients received induction therapy while 2(6%) patients were referred to hospice without receiving any treatment because of their general condition. These 2 patients were excluded from further analyses. 26(87%) of treated patients received Hyper-CVAD (7 received <4 cycles because of side effects and 19 >4 cycles) while others received different ALL-type regimens. 2(6%) patients underwent upfront consolidation with allo-BMT after induction chemotherapy. CR rate was 67% and PR 21%. 13 patients are alive with a median follow up of 63 months (95% CI 75-147). Of the 2 patients treated with allo-BMT one is alive in CR and the other presented CNS relapse after transplant and died of septic shock. Median overall survival (OS) of treated patients was 26 months (95% CI 34-79) and median progression free (PFS) was 21 months (95% CI 29-73). 3-year and 5-year OS rates were both 44% (95% CI 26-61%). 3-year and 5-year PFS rates were 45% (95% CI 26-61%) and 40% (95% CI 22-58%), respectively. Two patients (6%) developed CNS relapse. OS was statistically significantly longer in patients receiving more than 4 cycles of hyper-CVAD (p=0.05). No statistically significantly difference in OS and PFS was associated with following variables: ethnicity, BM involvement, IPI score, stage, presence of bulky disease, ECOG performance status and treatment with mediastinal RT. Patients treated with Hyper-CVAD demonstrated following responses: 17 (65%) achieved CR (95% CI 36-106) and 6(23%) PR (95% CI 0.54-46). Of those who achieved CR 11 are still alive in continuous CR and 6 patients died. Median OS was 26 months (CI: 29-76 months) and median PFS was 21 months (CI: 24-66 months) for Hyper-CVAD treated patients. In these patients 3-year OS and PFS were 44% (95% CI 24-62%) and 44% (95% CI 24-62%), respectively.

CONCLUSIONS: Our study describes characteristics and outcomes of patients (mainly indigent) living in Miami area and treated at UM with no referral bias. Many of these patients did not have medical insurance, preventing upfront consolidation with BMT. The observed remission, OS and PFS rates were inferior to rates reported in the literature. However, similar to previous reports, the incidence of CNS relapses was low, suggesting that appropriate intrathecal CNS prophylaxis together with systemic chemotherapy agents penetrating CNS are adequate for CNS prophylaxis. However, our results in this unbiased cohort suggest that either current chemotherapy treatments need be consolidated upfront with BMT or more efficient regimens are needed.