Jonathon B. Cohen

Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: A multicenter retrospective analysis

Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

Complete response to induction therapy in patients with Myc-positive and double-hit non-Hodgkin lymphoma is associated with prolonged progression-free survival.

Myc‐positive B‐cell non‐Hodgkin lymphoma (NHL) with or without a B‐cell chronic lymphocytic leukemia/lymphoma 2 (BCL2) rearrangement is associated with inferior progression‐free survival (PFS) and overall survival (OS). In this study, the authors reviewed the outcomes of patients with myc‐positive and double‐hit NHL at The Ohio State University.

Association of pre-transplantation positron emission tomography/computed tomography and outcome in mantle cell lymphoma.

Positron emission tomography/computed tomography (PET/CT)-positive findings before autologous SCT (auto-SCT) are associated with inferior PFS and OS in patients with relapsed Hodgkin’s and diffuse large B-cell lymphoma. We classified pre-transplant PET/CT performed before auto-SCT as positive or negative to evaluate the impact of pre-transplant PET/CT in mantle cell lymphoma (MCL). In 29 patients, 17 were PET/CT(−) and 12 were PET/CT(+). PET/CT(+) patients were younger (P=0.04), had lower MCL International Prognostic Index (MIPI, P=0.04) scores, but increased bulky adenopathy >5u2009cm (45% vs 13%, P=0.09). With a median follow-up of 27 months (range: 5–55 months), 7 patients relapsed (4 in the PET/CT(−) group and 3 in the PET/CT(+) group) with 2 deaths in the PET/CT(+) group without a documented relapse. The estimated 2-year PFS was 64% (95% confidence interval (CI): 0.30–0.85) vs 87% (95% CI: 0.57–0.97) in PET/CT(+) and PET/CT(−) patients, respectively (P=0.054). OS was significantly decreased in PET/CT(+) patients (P=0.007), with 2-year estimates of 60% (95% CI: 0.23–0.84) vs 100% in PET/CT(−) patients. A positive pre-transplant PET/CT is associated with a poor prognosis in patients with MCL. Additional factors may impact the prognostic value of PET/CT, as several PET/CT(+) patients remain in remission.

Complex Karyotype Is Associated With Aggressive Disease and Shortened Progression-Free Survival in Patients With Newly Diagnosed Mantle Cell Lymphoma

BACKGROUNDnPretreatment cytogenetics are not routinely used to predict patient outcomes in mantle cell lymphoma (MCL). Based on the prognostic utility of cytogenetics in other diseases, we reviewed the effect of a complex karyotype (CK) in MCL.nnnPATIENTS AND METHODSnWe included patients evaluated between November, 2002, and May, 2011. Those with ≥ 3 chromosomal abnormalities on a pre-treatment cytogenetic evaluation were defined as CK. Demographic, clinical, and survival differences between patients with CK and non-CK (NCK) were assessed.nnnRESULTSnOf 80 patients, 32 (40%) had CK, which was associated with high-risk clinical risk factors. Therapy did not differ between the groups, nor did rate of autologous stem cell transplant (ASCT). The 2-year progression-free survival (PFS) estimates were 70% and 48% for patients with NCK and CK, respectively (P = .02). Two-year overall survival (OS) estimates were also greater in those with NCK versus CK (85% vs. 58%; P = .02). When controlling for high-risk Mantle Cell Lymphoma International Prognostic Index (MIPI) score (P = .006), bulky disease (P = .01), and ASCT in first remission (P = .01), CK was not significantly associated with PFS (P = .18).nnnCONCLUSIONnCK is associated with shortened PFS and OS in MCL but has not been demonstrated to be prognostic independent of other variables in this series.

Hearing Loss due to Infiltration of the Tympanic Membrane by Chronic Lymphocytic Leukemia

Central nervous system (CNS) involvement by chronic lymphocytic leukemia (CLL) can present with dramatic neurologic findings or can be quite subtle, discovered only at the time of autopsy. We describe a case of CLL in a patient who presented initially with hearing loss and was ultimately found to have involvement of the tympanic membrane. She noted improvement of her hearing after induction therapy but was not aware at the time of the involvement of her CNS with CLL. Upon worsening of hearing at the time of relapse, she was evaluated by imaging and CSF analysis as well as biopsy of the tympanic membrane, and involvement of the CNS was confirmed. She has received CNS-directed therapy with intrathecal liposomal cytarabine and intravenous CNS-directed therapy and has noted improved hearing and resolution of her imaging and CSF findings. This is the first reported case of tympanic membrane involvement with CLL and describes potentially effective methods for managing this challenging complication.

Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma

Patients with double-hit lymphoma (DHL), which is characterized by rearrangements of MYC and either BCL2 or BCL6, face poor prognoses. We conducted a retrospective multicenter study of the impact of baseline clinical factors, induction therapy, and stem cell transplant (SCT) on the outcomes of 311 patients with previously untreated DHL. At median follow-up of 23 months, the median progression-free survival (PFS) and overall survival (OS) rates among all patients were 10.9 and 21.9 months, respectively. Forty percent of patients remain disease-free and 49% remain alive at 2 years. Intensive induction was associated with improved PFS, but not OS, and SCT was not associated with improved OS among patients achieving first complete remission (P = .14). By multivariate analysis, advanced stage, central nervous system involvement, leukocytosis, and LDH >3 times the upper limit of normal were associated with higher risk of death. Correcting for these, intensive induction was associated with improved OS. We developed a novel risk score for DHL, which divides patients into high-, intermediate-, and low-risk groups. In conclusion, a subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.