Aggressive non‐Hodgkin lymphoma (NHL) is among the most common cancers in sub‐Saharan Africa (SSA), where CHOP is standard treatment and outcomes are poor. To address this, we treated 17 newly diagnosed adult patients in Malawi with Burkitt (n = 8), plasmablastic (n = 8), and primary effusion lymphoma (n = 1) with a modified EPOCH regimen between 2016 and 2019. Twelve patients (71%) were male and the median age was 40 years (range 16‐63). Eleven (65%) were HIV infected, median CD4 count was 218 cells/µL (range 9‐460), and nine (82%) had suppressed HIV RNA < 400 copies/mL. Patients received a median of six cycles (range 2‐8) and median follow‐up was 14 months (range 2‐34) among patients still alive. Grade 3/4 neutropenia was observed in 26% of cycles and in 65% of patients. Sixteen (94%) responded to EPOCH and 10 (59%) achieved a complete response. One‐year overall survival (OS) was 62% (95% confidence interval [CI], 42%‐91%). Five patients (29%) died from progressive NHL and three (18%) from treatment‐related complications. These data suggest EPOCH with setting‐appropriate modifications may be a practical, safe, and effective option for improving high‐risk NHL outcomes in Malawi and comparable settings, which deserves further prospective evaluation.
We describe 41 cases of myeloid neoplasms (MNs) secondary to plasma cell myeloma (PCM). The types of MN included myelodysplastic syndrome (MDS) in 34 (82.9%), acute myeloid leukemia (AML) in 4 (9.8%), and myeloproliferative neoplasm (MPN) or MDS/MPN in 3 (7.3%) cases. The latency from treatment to diagnosis of MN ranged from 9 to 384 months, with a median of 60 months. Of 37 cases with cytogenetic studies, complex abnormalities were detected in 22 (59.5%), -5(q)/-7(q) in 4 (10.8%), other abnormalities in 8 (21.6%), and normal karyotype in 3 (8.1%) cases. Complex abnormalities and -5(q)/-7(q) correlated directly with multiple chemotherapeutic regimens, particularly with combined melphalan/cyclophosphamide. Moreover, the features of cytogenetic abnormalities in our series were significantly different from those with concomitant PCM/MN who had significantly lower complex abnormalities. The latency, skewed proportion of MDS, and bias toward complex cytogenetic abnormalities/unbalanced aberrations of chromosomes 5/7 suggested an alkylating mutagenic effect on pathogenesis of secondary MN. Kaplan-Meier survival analysis demonstrated a median survival of 19 months, which was better than that for therapy-related (t)-MDS/AML. In contrast to t-MDS, the survival in our patients appeared to depend on subtypes of MDS as seen in de novo diseases.
A 17-year-old boy, with acute myelomonocytic leukemia and inversion 16(p13q22) developed polyneuropathy and isolated central nervous system relapse. Scoliosis and high-arched feet suggested a diagnosis of Charcot Marie Tooth (CMT) syndrome and genetic testing confirmed duplication at the PMP22 locus at chromosome 17p11.12. No mutation was found in another CMT gene, the CMT C1 LITAF locus at 16p13.2, to suggest that this association is anything more than chance. Titres to VGKC, a paraneoplastic autoantibody, were elevated, suggesting an additional mechanism for the polyneuropathy. This case extends the clinical spectrum of cancer with CMT, and of paraneoplastic disorders.
Donor CD4 + CD25 + FOXP3 + regulatory T cells (Treg) are capable of suppressing immune-mediated graft-versusleukemia (GvL) and graft-versus-host disease (GvHD) responses. We undertook a dose-finding phase 1 study of CD25-depleted donor lymphocyte infusions (DLI) to treat post-transplantation relapse. Methods: 24 subjects with disease relapse after HLAmatched allogeneic transplantation (9 AML, 4 ALL, 4 HD, 2 MDS, 2 NHL) were enrolled. Patients had no evidence of GvHD, were on no systemic immunosuppressants, and had received no salvage chemotherapy in the 4 weeks preceding DLI. Donor lymphocytes were CD25+ depleted via the Clin-iMACS system (Miltenyi). Primary objectives were feasibility and safety. Secondary objective was response. Results-Feasibility: 3 patients came off study for insufficient numbers of donor CD3+ cells or GvHD onset prior to DLI. In the remainder, 10 had persistent or progressive disease, 7 were in PR, and 4 were in CR at study entry. CD25-depleted DLI doses were 1x10 7 CD3 + cells/kg (level 1; n¼5) and 3x10 7 CD3 + cells/kg (level 2; n¼16). 8 DLIs were from unrelated donors, 13 from related donors. Median log-reductions of CD25 + and CD4 + CD25 + FOXP3 + Treg cells in the infusion products were 1.24 (range 0.72-7.75) and 2.10 (range 1.17-6.46), respectively. Safety: 16 of 21 subjects were evaluable for toxicity. In 3 evaluable subjects at DLI Level 1, there were no DLTs. Dose Level 2 was the MTD, with 1 case of fatal acute GvHD in 13 evaluable subjects. Among all subjects, rates of acute or chronic GvHD were 19% by 8 weeks and 38% by 1 year following DLI. Response: Median follow-up is 29.5 months. All subjects at Dose level 1 had progressive disease at 8 weeks; 1 experienced extensive chronic GvHD. At Dose level 2, 8 subjects (50%) had a response (1 PR, 7 CR), including 6 who had evidence of disease at DLI. 6 subjects, including 5 responders, manifested GvHD by day 100. 1 year survival was 8/16 (50%) in the MTD cohort, with 4 of the initial 8 week responders still in CR. Median survival was 15.4 months. Conclusions: Use of CD25 + Treg depleted DLI appears feasible, safe and capable of inducing GvL without excessive GvHD in hematologic malignancies relapsed after allotransplantation. Its safety and preliminary efficacy is promising but needs future prospective evaluation.
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