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Background Acquired or immune-mediated TTP (iTTP) is a life-threatening thrombotic microangiopathy, characterized by the presence of microangiopathic hemolytic anemia and severe thrombocytopenia, and a variable degree of ischemic organ damage, related to a severe deficiency of ADAMTS13, which is a serine metalloprotease necessary for cleavage of large vWF multimers. There has been a dramatic decrease in mortality rates with the recognition of the pathophysiology of iTTP over the years. Although therapeutic plasma exchange (TPE) together with corticosteroids are the backbone of the upfront treatment of patients with iTTP with successful outcomes, patients may remain refractory and/or relapse following an initial response to this treatment. Methods We performed a review regarding the pathogenesis, diagnosis, treatment strategies, monitoring, and prognosis of iTTP. Results There are several new treatment strategies, which can be used among these patients, helping in improving outcomes of iTTP. Rituximab has been shown to be a safe and effective adjunct to TPE, especially in patients with refractory and/or relapse as well as it is increasingly used preemptively to prevent exacerbation or recurrence. Recently, caplacizumab, a nanobody targeting vWF, was approved as an addition to the current regimen of TPE and immunomodulation for patients of iTTP. Conclusion Specific predictors of relapse in patients in remission can be relevant for an optimal patient management. Different models including ADAMTS13 biomarkers can provide a new screening strategy to identify patients who may predict outcomes and the risk of relapse, benefit from preemptive therapy prior to relapse.

Acute myeloid leukaemia (AML) is a haematopoietic stem cell disorder, that is characterized by the clonal expansion of myeloid blasts and suppression of normal haematopoiesis. The 3 + 7 regimen is the backbone of standard first-line induction therapy among young/fit patients. However, in elderly and/or unfit patients with newly diagnosed AML, who cannot receive intensive chemotherapy, low-dose cytarabine or hypomethylating agents (azacitidine or decitabine) are the treatment options, which generally cannot induce durable responses. Among young/fit patients, for high-risk disease in first remission, or in cases with relapsed/refractory AML, allogeneic stem cell transplantation should be performed when complete remission is achieved. However, since AML is primarily a disease of the elderly, neither intensive chemotherapy nor allogeneic stem cell transplantation can be generally tolerated in most cases. There is clearly a need for new treatment options in elderly and young/unfit patients who cannot receive intensive chemotherapy. The discovery of novel molecular genetic markers (e.g. FMS-like tyrosine kinase 3, isocitrate dehydrogenase 1 and 2) resulted in the development of new therapeutic options in AML. This review mainly focuses on 4 targeted therapy agents; glasdegib and venetoclax used in combination treatment with low-dose cytarabine or hypomethylating agents among newly diagnosed cases with AML; and ivosidenib and gilteritinib as monotherapy in the treatment of relapsed/refractory AML, which were all approved by the US Food and Drug Administration in 2018.

Eskazan, Ahmet Emre/0000-0001-9568-0894 WOS:000568513300001 PubMed ID: 32896091 Background Therapy-related leukemia is a well-recognized clinical syndrome. Peptide receptor radionuclide therapy (PRRT) is a modern therapeutic approach using radionuclide combined with somatostatin analog peptide for inoperable or metastatic neuroendocrine tumors. Aims Hematologic toxicities including late-onset myeloid neoplasms have been reported after PRRT; however, therapy-related chronic myeloid leukemia (TR-CML) following PRRT is a relatively rare entity. Methods We present a 64-year-old male who received PRRT for pancreas neuroendocrine tumor and then developed TR-CML 60 months after the initiation of PRRT. The patient responded well to imatinib therapy. Results Patients with TR-CML generally have similar tyrosine kinase inhibitor responses and outcomes when compared to de novo cases. Conclusions The physicians should be aware of the short- and long-term hematologic toxicities of PRRT including TR-CML, and careful monitoring is mandatory in this group of patients.

Background: The coronavirus disease 2019 (COVID-19) pandemic has brought life to a standstill all over the world. Especially in Istanbul, the most populated city in Turkey, many hospitals served as pandemic hospitals and suspended the examination of patients who were not infected with COVID-19. On the other hand, in this period, lockdown was applied frequently to control the pandemic and to reduce the transmission. It is known that the delay in the diagnosis and treatment of cancer can sometimes be fatal. Initial treatment choice in classical Hodgkin lymphoma (cHL) patients is determined by various factors including the stage of the disease. Therefore, detection of the disease at an early stage has prognostic importance. Our aim was to compare the time from symptom onset to diagnosis and period between diagnosis and treatment initiation, as well as the distribution of stages and treatment responses in cHL patients diagnosed and treated during the COVID-19 pandemic and in the pre-pandemic period. Methods: Patients who were diagnosed within the 2 years before the pandemic (between March 2018 and March 2020) and in a 12-month period during the pandemic (between March 2020 and March 2021) were compared in terms of demographic data, disease related factors, time interval between symptom to diagnosis, and interim treatment response. Clinical data were obtained from manual and electronic medical records retrospectively. PET scans were performed at baseline, after two cycles of chemotherapy, and end of treatment (EOT). The Deauville five-point scale (5-PS) was used in the initial staging and assessment of treatment response. The 5-PS; a score of 1, 2, or 3 was considered negative. The 5-PS score 4 or 5 was positive. Results: This single-center study included 90 newly diagnosed cHL patients, with a median age of 33.5 years (range, 17 - 70 years) and a male predominance (53.3%). The most common presenting symptom was a lump in the neck (41.1%), and also, 61.1% (n=55) of the cases had at least one B symptom. Patient characteristics were summarized in Table 1. Age and sex distributions were similar in both groups. Also, the number of patients >60 years was comparable (p=0.868). The most common histopathological subtype in both groups was nodular sclerosis (47.7% vs. 48%). In the pre-pandemic period and during the pandemic, the percentages of patients with early unfavorable disease were 66.7% and 77.8%, respectively (p=0.526). Although the percentage of patients with advanced-stage disease was higher during the pandemic than that observed in the pre-pandemic period (64% vs. 53.8%), this difference did not reach statistical significance (p=0.384). The median interval between symptom onset to diagnosis was significantly longer during the pandemic than was observed within the pre-pandemic era (16 weeks vs. 8 weeks, p=0.042). The median durations between diagnosis and treatment initiation were similar in both groups (13 days vs. 15 days, p=0.253). The majority of patients in both groups received ABVD as first-line therapy, and IFRT was performed in some patients with early-stage cHL (Figure 1). Among all patients (n=90), 85% of the cases had negative interim PET scan results, and this percentage was similar for both patient groups (84.6% vs. 88%, p=0.999). In the pre-pandemic period, 80% of the patients had complete response at EOT, on the other hand, no comparison was performed between two groups regarding response level at EOT, since nearly half of patients (48%) treated during the pandemic were not evaluated for the EOT response at the time of the analysis. Discussion & Conclusion: In our cohort, the time interval between symptom onset to diagnosis was significantly prolonged during the pandemic. Most probably the patients were afraid of admitting to the hospital due to the fear of contagion, or patients might have experienced difficulties in applying to a health facility, and lastly maybe they had tolerable symptoms, which might all have roles in the diagnostic delay during the pandemic. Higher percentage of patients with advanced-stage disease during the pandemic might also be associated with this delay, however, fortunately, this difference did not translate into a significant difference regarding interim treatment response in both groups. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Treatment for relapse of chronic myeloid leukemia (CML) following hematopoietic cell transplantation (HCT) includes tyrosine kinase inhibitors (TKI) with or without donor lymphocyte infusions (DLI), however the most effective treatment strategy is unknown. This study was performed through the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We retrospectively reviewed all patients reported to the CIBMTR registry from 2002–2014 who underwent HCT for CML and were alive 30 days post relapse. A total of 215 HCT recipients relapsed and were analyzed in the following groups 1) TKI alone n=128, 2) TKI with DLI n=48, and 3) DLI without TKI n=39. In multivariate analysis, disease status prior to HCT had a significant effect on overall survival (OS). Patients that received a DLI alone compared to a TKI with DLI had inferior survival HR 2.28 (95% CI 1.23–4.24; p = 0.009). Those who received TKI alone had similar survival compared to those who received TKI with DLI (p=0.81). These data supports that despite use of TKI pre-transplantation, TKI salvage therapy continues to provide significant survival following relapse in patients with CML following HCT. These data does not suggest that adding a DLI to TKI adds an improvement in OS.

Background: Ibrutinib has become a widely used drug in the management of B-cell lymphoproliferative neoplasms (BLPNs). Past or active HBV infection is an exclusion criteria for the clinical trials of ibrutinib and for patients (pts) treated outside clinical trials there are contradictory data or suggestions concerning hepatitis B virus (HBV) prophylaxis. In this study, we evaluated the real-life data on the outcome of HBV infection status of pts with BLPNs receiving ibrutinib. Methods: Demographic features, previous treatments (including rituximab (RTX)) and follow-up durations, HBV infection and reactivation status, prophylaxis information, serum transaminase and total bilirubin levels of the pts were noted retrospectively. Past HBV infection was defined as concurrent detectable HBV core IgG antibody (Ab) (anti-HBc IgG) and undetectable HBV surface Ag (HbsAg) ± HBV surface Ab (anti-HBs). Active HBV infection was defined as HbsAg and/or HBV core IgM Ab (anti-HBc IgM) positivity. Quantitative HBV-DNA PCR results are also recorded, when available. Results: Twenty-seven consecutive pts were included, and pts' characteristics are displayed in Table 1. Median durations of ibrutinib therapy and entire follow-up were 9 and 108 months, respectively. All pts had received RTX prior to ibrutinib. Among the 27 patients, 8 had past HBV infection, while 2 had active HBV infection. HBV prophylaxis or treatment was started before ibrutinib in 5 pts, and simultaneously with ibrutinib in one. The remaining 4 pts with past HBV infection were not given any prophylaxis. Among these 4 cases with anti-HBc IgG positivity, three were also positive for anti-HBs. Currently, these 4 pts, including the one with a negative anti-HBs status, are at the 2nd, 4th, 12th, and 16th cycles of ibrutinib. To date, no signs of HBV reactivation was detected in our cohort. Discussion & Conclusion: All pts in our cohort had received RTX containing regimens prior to ibrutinib. In our analysis, 5 pts were under HBV prophylaxis or treatment when ibrutinib was started. Two of these had active HBV infection. Simultaneous HBV prophylaxis was started with ibrutinib for one pt and the remaining 4 pts with past HBV infection (anti-HBs + anti-HBc IgG positivity) did not receive any prophylaxis, but they were planned to be followed by monitoring the anti-HBs titers. In a study, 21 BLPN pts (10 treated with RTX previously) with occult HBV infection with a median follow-up of 9.5 months treated with ibrutinib without anti-HBV prophylaxis, and only two HBV reactivations were reported (Hammond et al. Blood. 2018;131(17):1987-1989). In another study, no HBV reactivation was detected in 7 CLL pts with past HBV infection, with a median follow-up duration of 25 months under ibrutinib, without any anti-viral prophylaxis (Tedeschi et al. Leuk Lymphoma. 2017; 58(12):2966-2968). The increase in the number of pts treated with ibrutinib, is followed by the awareness about the infectious complications including HBV reactivation. The consecutive use of RTX and ibrutinib has increased the risk of HBV-related complications. This issue has become more important in areas with a higher prevalence of HBV. Although the number of pts is limited and follow-up periods are relatively short, our results may indicate that pts with occult HBV infection treated with ibrutinib for BLPNs, might only be closely followed for HBV reactivation, rather than routine anti-HBV prophylaxis. Since pts with previous RTX exposure are likely to lose anti-HBs antibodies, ibrutinib-treated pts with both anti-HBs and anti-HBc IgG positivity should be closely monitored for possible risk of HBV reactivation. Anti-viral prophylaxis under ibrutinib therapy might still be an option for the selected cases. Disclosures No relevant conflicts of interest to declare.