<Introduction> Tumor-lysis syndrome (TLS) describes a group of metabolic disturbances caused by the massive and abrupt release of cellular components into the blood after the rapid lysis of malignant cells. TLS is a potentially life-threatening complication in rapidly proliferating, bulky tumor, or highly chemo-radiosensitive cancers. In contrast, TLS is the rare complication among patients with multiple myeloma (MM). TLS seems to occur more frequently in MM patients receiving bortezomib (BOR) and carfilzomib (CFZ) than in those receiving other cytotoxic agents. We retrospectively investigated the frequency, risk factors, and clinical outcome among the relapsed or refractory MM (RRMM) patients treated with proteasome inhibitors (PI), such as BOR, CFZ, and ixazomib (IXA), in our institute. <Methods> Between November 2005 and December 2017, seventy-two RRMM myeloma patients treated with BOR, CFZ, or IXA, in our institute. The number of patients treated PI was defined as below. Relapse or refractory disease and response criteria were defined according to the International Myeloma Working Group criteria. Patients with monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and primary plasma cell leukemia were excluded. We evaluated TLS by the Cario-Bishop grading classification. After starting of PI, the following parameters were recorded and evaluated for prognosis: serum hemoglobin concentration (Hb), serum level of lactate dehydrogenase (LDH), creatinine (Cr), uric acid (UA). The cutoff levels of LDH, Cr, and UA were the upper normal limit. Anemia was defined by the CRAB criteria. Hepatosplenomegaly and plasmacytoma were evaluated using computed tomography. We analyze these two groups in terms of patient characteristics, laboratory findings, response, and survival. Fisher's exact tests were used to compare differences between the two groups. We analyzed prognostic factors for survival in significant poor predictors of laboratory parameters and well-established prognostic factors by Cox regression analysis. Overall survival (OS) and time to next treatment (TTNT) were analyzed by the Kaplan-Meier method. <Results> Median age of the patients was 71 years (range, 41-86) at the time of PI treatment. Median number of prior treatments was 2 (range, 1-8). The number of patients treated 53 of BOR, 10 of IXA, 4 of BOR + CFZ, 3 of CFZ + IXA, 1 of BOR + IXA, and 1of BOR + CFZ + IXA, respectively. TLS occurred in 13 patients (18.1%); such as 8 of BOR (13.3%), 4 of CFZ (40.0%), and 1 of IXA (6.7%). TLS occurred more frequently in the patients treated with twice weekly CFZ plus dexamethasone (CFZ 56mg/m2) than twice weekly CFZ, lenalidomide, plus dexamethasone (CFZ 27mg/m2); 50% and 25%, respectively. Median day of TLS after PI was 8 (range, 4-21). Median day of TLS in BOR, CFZ, and IXA were 7.5, 5.5, and 13 days, respectively. Two patients received rasbricase after TLS occurred. There was no patient who underwent hemodialysis for TLS. The mortality related with TLS was none. The significant factors associated TLS were anemia, high LDH level, prior treatments of 2 or more and hepatosplenomegaly according to univariate analysis. In multivariate analysis, high LDH level (Odds ratio; 12.9, P=0.027) and hepatosplenomegaly (Odds ratio; 13.4, P=0.035) was related with TLS significantly. There was no significant difference between overall response rate in the TLS group and non-TLS group (46.4% vs 64.8%, P=0.117). In median follow-up was 12.9 months, the median TTNT of the TLS group was significantly shorter than that of the non-TLS group (1.9 vs 7.0 months, P = 0.009, Figure 1a). The median OS of the TLS group was significantly shorter than that of the non-TLS group as well (5.8 vs 46.4 months, P = 0.017, Figure 1b). <Conclusion> Our analysis revealed that 18.1% of RRMM patients treated with PI developed TLS although TLS was manageable by prophylaxis.gh LDH level and hepatosplenomegaly were identified with significant risk factors for TLS. TLS was not associated with good response of treatment. The TTNT and OS in the TLS group was significantly shorter than those in the non-TLS group. We considered that TLS might be related with progressive disease without activity of treatment in RRMM patients treated with PI. Among the RRMM patients with high LDH level, TLS is one of common adverse events in first cycle of PI but tolerable. Disclosures No relevant conflicts of interest to declare.
Although some patients with COVID-19 develop only mild symptoms, fatal complications have been observed among those with comorbidities. As patients with cancer are immunocompromised, they are thought to have a high risk of severe illness associated with COVID-19. We report a COVID-19 patient with adult T-cell leukemia-lymphoma (ATL) who was treated using favipiravir. A 69-year-old woman with lymphoma-type ATL was treated using cyclophosphamide, doxorubicin, vincristine, prednisolone and mogamulizumab (M-CHOP) with substantial efficacy. However, in cycle 4 of M-CHOP therapy, she developed fever with mild cough. The patient was admitted to the hospital and CT revealed bilateral ground-glass opacities. SARS-CoV-2 was detected by RT-PCR and the patient was diagnosed with COVID-19. Considering severe immunosuppression caused by ATL, we initiated favipiravir therapy. Subsequently, the fever improved without antipyretics and her C-reactive protein level decreased rapidly. SARS-CoV-2 PCR tests were negative on days 17 and 18 of favipiravir therapy, and the patient was discharged without residual disease on the final CT. This is the first documented case of COVID-19 in a patient with ATL. Although severe immunosuppression caused by ATL was present, severe COVID-19 pneumonia did not develop. The immunosuppressed condition caused by hematological malignancy may not always be a risk factor for severe illness associated with COVID-19. Further accumulation of data regarding COVID-19 in patients with hematological malignancies is warranted to clarify the risk factors for severe illness, the best-in-class antiviral agent, and the optimal treatment strategy in this population.
The diagnosis of histological transformation of follicular lymphoma can be challenging and ambiguous. We investigated the distribution of the Ki-67 labeling index of histological transformation of follicular lymphoma and determined its cutoff value to predict poor outcomes. The diagnostic criteria for histological transformation were a diffuse pattern of proliferation and a proportion of large lymphoma cells ≥20%. Of the 1121 patients with follicular lymphoma, 171 (15%) showed histological transformation to diffuse large B-cell lymphoma. Of these, 76 patients, whose biopsies were obtained from the sites with the highest maximum standardized uptake values, according to the positron emission tomography findings, were included. The Ki-67 index ranged from 16.8% to 98.4% (median, 60.6%). In patients with histological transformation, the most significant differences were found in progression-free survival (p = 0.087, 58% vs. 87% at 2 years) and overall survival (p = 0.024, 53% vs. 85% at 5 years) when a 70% cutoff was used. Additionally, overall survival was significantly shorter in patients with histological transformation with maximum standardized uptake values of ≥20 (p < 0.0001) and absence of a follicular lymphoma component (p = 0.004). A Ki-67 index of ≥70% was a significant adverse factor for overall survival in patients with histological transformation of follicular lymphoma and may predict poor outcomes.
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