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High-grade B-cell lymphoma (HGBL) with translocations involving MYCand BCL2or BCL6comprises ∼10% of cases of diffuse large B-cell lymphoma (DLBCL) and carries a poor prognosis. The incidence, prognosis, and optimal therapy for DLBCL harboring extra copies of the genes MYC, BCL2, and BCL6, rather than their genetic translocations, are unknown. In this retrospective, single-center study we identified 144 DLBCL cases including 46 patients with classic HGBL with double-hit or triple-hit chromosomal translocations (DHL), 55 with extra copies of MYCin addition to aberrations (extra copies or translocations) of BCL2and/or BCL6but did not meet the criteria for HGBL (EC group), and 43 without any aberrations of MYC, BCL2,or BCL6(wild type [WT]). Unfavorable baseline characteristics had similar frequency in the EC and WT groups, but were significantly more prevalent in the DHL group. With a median follow-up of 36 months, the 2-year event-free survival (EFS) was similar between the WT and EC groups at 77% (95% confidence interval [CI], 65-90) and 82% (95% CI, 72-93), respectively. In contrast, the 2-year EFS of the DHL group was 63% (95% CI, 51-79). The 2-year overall survival in the WT, EC, and DHL groups was 86% (95% CI, 76-97), 89% (95% CI, 81-98), and 74% (95% CI, 62-88), respectively. Among patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the EC group had outcomes similar to those of the WT group. Our results indicate that patients with DLBCL with extra gene copies of MYC, BCL2, and BCL6fare differently from those with HGBL and respond well to standard R-CHOP therapy.

Quality of immune reconstitution after cord blood transplantation (CBT) without antithymocyte globulin (ATG) in adults is not established. We analyzed immune recovery in 106 engrafted adult CBT recipients (median age 50 years [range 22-70]) transplanted for hematologic malignancies with cyclosporine/mycophenolate mofetil immunoprophylaxis and no ATG. Patients were treated predominantly for acute leukemia (66%), and almost all (96%) underwent myeloablation. Recovery of CD4+T cells was faster than CD8+T cells with median CD4+T-cell counts exceeding 200/mm3at 4 months. Early post-CBT, effector memory (EM), and central memory cells were the most common CD4+subsets, whereas effector and EM were the most common CD8+T-cell subsets. Naive T-cell subsets increased gradually after 6 to 9 months post-CBT. A higher engrafting CB unit infused viable CD3+cell dose was associated with improved CD4+and CD4+CD45RA+T-cell recovery. Cytomegalovirus reactivation by day 60 was associated with an expansion of total, EM, and effector CD8+T cells, but lower CD4+T-cell counts. Acute graft-versus-host disease (aGVHD) did not significantly compromise T-cell reconstitution. In serial landmark analyses, higher CD4+T-cell counts and phytohemagglutinin responses were associated with reduced overall mortality. In contrast, CD8+T-cell counts were not significant. Recovery of natural killer and B cells was prompt, reaching medians of 252/mm3and 150/mm3by 4 months, respectively, although B-cell recovery was delayed by aGVHD. Neither subset was significantly associated with mortality. ATG-free adult CBT is associated with robust thymus-independent CD4+T-cell recovery, and CD4+recovery reduced mortality risk.