Monoclonal gammopathy and serum immunoglobulin levels as prognostic factors in chronic lymphocytic leukaemia

The relationship between chronic lymphocytic leukaemia (CLL) and qualitative/quantitative gammaglobulin abnormalities is well established. Nevertheless, in order to better understand this kind of connection, we examined 1505 patients with CLL and divided them into four subgroups on the basis of immunoglobulin (Ig) aberrations at diagnosis. A total of 73 (4\ub78%), 149 (10%), 200 (13\ub72%) and 1083 (72%) patients were identified with IgM monoclonal gammopathy (IgM/CLL), IgG monoclonal gammopathy (IgG/CLL), hypogammaglobulinaemia (hypo-\u3b3) and normal Ig levels (\u3b3-normal) respectively. IgM paraprotein was significantly associated with a more advanced Binet/Rai stage and del(17p)/TP53 mutation, while IgG abnormalities correlated with a higher occurrence of trisomy 12. Patients with any type of Ig abnormality had shorter treatment-free survival (TFS) but no significant impact affecting overall survival (OS) compared to those with normal Ig levels

Safety and efficacy of a dose-dense short-term therapy in patients with MYC-translocated aggressive lymphoma

Patients with aggressive B-cell lymphoma and MYC rearrangement at FISH exhibit poor outcome after R-CHOP. In the last decade, 68 patients with Burkitt lymphoma (BL; n=46) or high-grade B-cell lymphoma (single, double or triple hit; HGBCL; n=22) were treated with a dose-dense, short-term therapy termed "CARMEN regimen", at five Italian Centers. Forty-six (68%) patients were HIV-positive. CARMEN included a 36-day induction with sequsingle weekly doses of cyclophosphamide, vincristine, rituximab, methotrexate, etoposide, and doxorubicin plus intrathecal chemotherapy, followed by high-dose-cytarabine-based consolidation. Patients who did not achieve complete remission (CR) after induction received BEAM-conditioned ASCT after consolidation. Sixty-one (90%) patients completed induction and 59 (87%) completed consolidation. Seventeen patients received ASCT. Grade-4 hematological toxicity was common but did not cause treatment discontinuation; grade-4 non-hematological toxicity was recorded in 11 (16%) patients, with grade-4 infections in 6 (9%). Six (9%) patients died of toxicity (sepsis in four, COVID-19, ARDS). CR rate after the whole treatment was 73% (95%CI=55-91%) for HGBCL patients and 78% (95%CI=66-90%) for BL patients. At a median follow-up of 65 (IQR 40-109) months, 48 patients remain event-free, with a 5-year PFS of 63% (95%CI=58-68%) for HGBCL and 72% (95%CI=71-73%) for BL, with a 5-year OS of 63% (95%CI=58-68%) and 76% (95%CI=75-77%), respectively. HIV seropositivity had not a detrimental effect on outcome. This retrospective study shows that CARMEN is a safe and active regimen both in HIV-negative and -positive patients with MYC-rearranged lymphomas. Encouraging survival figures, attained with a single dose of doxorubicin and cyclophosphamide, deserve further investigation in HGBCL and other aggressive lymphomas