Prevention of pneumocystis pneumonia in patients with hematological diseases: Efficacy of low-dose atovaquone.

OBJECTIVE: At our institution, patients with hematological disease who require Pneumocystis jirovecii pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there have been few reports on the efficacy of low-dose atovaquone administration, and the purpose of this study is, therefore, to investigate its effectiveness. MATERIALS AND METHODS: We investigated the expression of PJP in patients with hematological disease who received atovaquone administration. Atovaquone was administered at a low dose of 750 mg once daily, and the follow-up time was the period of PJP prophylaxis that included atovaquone administration. RESULTS: 85 patients were included in the study. The median age of the study population was 72 years (range: 33 - 97). The duration of atovaquone treatment and follow-up time were 150 days (22 - 1,018) and 258 days (22 - 1,457), respectively. In hematologic diseases, multiple myeloma was high in 31 patients and malignant lymphoma in 28 patients. No patients exhibited PJP during the observation period. CONCLUSION: In hematological disease patients with relatively low risk of PJP, low-dose atovaquone may prevent the onset of PJP.

[Analysis of anti-SARS-CoV-2 IgG antibody titers after mRNA booster vaccination in patients with nonmalignant hematological disorders].

In our facility, anti-SARS-CoV-2 mRNA vaccines were given to 21 patients, including 8 with aplastic anemia (AA), 3 with pure red cell aplasia (PRCA), and 10 with immune thrombocytopenic purpura (ITP), and IgG antibody titers were assessed one month after vaccinations. After receiving both a second vaccine and a booster shot, all patients with AA/PRCA treated with cyclosporine A aside from one, had IgG titers that were lower than the median levels of healthy controls. Even if prednisolone (PSL) doses did not go over 10 mg/day, ITP patients receiving PSL therapy were unable to achieve adequate levels of IgG after booster immunizations.

Successful Elimination of SARS-CoV-2 Following Vaccination with BNT162b2 after Prolonged Viral Infection in an Immunocompromised Lymphoma Patient.

A 52-year-old man with mantle cell lymphoma treated with bendamustine and rituximab developed prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Despite elevated titers of anti-spike IgG antibody, protracted pancytopenia persisted for more than six months. Finally, the anti-SARS CoV-2 vaccine, BNT162b2, was administered, which improved his blood cell count and eliminated the virus. The increased anti-spike IgG titer and lymphocyte count after vaccination suggested that both humoral and cellular immunity acted in coordination to eliminate the virus.

[SARS-CoV2 anti-spike IgG response following COVID-19 mRNA vaccination (BNT162b2) in patients with hematological disorders].

This is a prospective study conducted to determine the level of anti-spike IgG to SARS-CoV-2 2-6 weeks following the BNT162b2 vaccination in 125 patients with hematological disorders. Compared with healthy controls, patients with malignant lymphoma had lower rates of seropositivity and lower levels of antibody titer. Furthermore, patients who received rituximab (R)-containing chemotherapy had lower antibody titers than those who were not treated with R or who had completed R-containing chemotherapy more than 9 months earlier. Despite having 71% IgG-seropositivity, patients with multiple myeloma had lower antibody titers than the control group. Furthermore, patients receiving daratumumab-containing chemotherapy had lower antibody titers than those not receiving treatment. Moreover, patients with acute myeloid leukemia or myelodysplastic syndrome had lower antibody titers than the control group. Overall, the number of peripheral blood lymphocytes was significantly correlated with IgG titers, with seropositive patients having more peripheral blood lymphocytes than seronegative patients. Patients with severe immunosuppression, such as those with hematological disorders, often have impaired seroconversion with COVID-19 vaccination that should be taken into consideration by clinicians.

Preceding bortezomib administration for a certain period reduces the risk of lenalidomide-induced skin rash.

WHAT IS KNOWN AND OBJECTIVE: It was previously reported that the incidence of lenalidomide (LEN)-induced skin rash is reduced by administration of bortezomib (BOR) prior to LEN administration in patients with multiple myeloma (MM). Therefore, we investigated whether LEN-induced skin rash is affected by the duration of BOR administration and the dosing interval between BOR and LEN administration. METHOD: A retrospective investigation was conducted among MM patients who received BOR treatment prior to LEN treatment in Eiju General Hospital from May 2010 to December 2020. We investigated whether the BOR administration duration and interval duration from the completion of BOR administration to the initial LEN administration affect the development of LEN-induced skin rash. RESULT AND DISCUSSION: Twenty-eight of the 81 patients exhibited LEN-induced skin rash (34.6%). The administered duration, but not the interval, was significantly longer in the group without skin rash. Cut-off values were set for the duration of administration and interval, which were 35 days and 30 days, respectively. Multivariate analysis was performed on patients which are administered duration of more than 35 days and intervals of less than 30 days, and those who are not applicable. A significant difference was observed in the incidence of skin rash for each factor. WHAT IS NEW AND CONCLUSION: The risk of reduced LEN-induced skin rash is affected not only by the presence of prior BOR administration, but also by the duration of BOR and the interval from the completion of BOR to the initial LEN administration.

Simple desensitization protocol for multiple myeloma patients with lenalidomide-induced skin rash: Case series.

WHAT IS KNOWN AND OBJECTIVE: Skin rash is one of the typical side effects of lenalidomide (LEN) treatment. Desensitization therapies have been reported to be effective in patients with severe skin rash caused by LEN. However, they have proved impractical due to the complexity of the protocols. CASE SUMMARIES: We present 5 patients who developed severe LEN-induced skin rash. The five patients received our simple, slow desensitization protocol, and all were re-administered LEN with no adverse reaction. WHAT IS NEW AND CONCLUSION: Our simpler and slow desensitization protocol, which desensitizes the patients without reducing the effect of LEN, includes drug holidays, similar to the usual LEN dosing schedule, and moreover is recommended as a treatment option especially for elderly patients with no housemate to help with medical management.

Analysis of risk factors for lenalidomide-associated skin rash in patients with multiple myeloma.

The aim of the present study was to identify the risk factors for lenalidomide (Len)-associated skin rash. We retrospectively investigated the medical records of 144 multiple myeloma patients treated with Len-containing therapies. A total of 64 of 144 patients included in the study had skin rash (44.4%). 50 patients developed skin rash within 4 weeks of starting Len treatment. Further, in 29 patients, the skin rash appeared at an early stage (within 1 week) after treatment initiation. Univariate analysis revealed that the risk of skin rash significantly increased in patients with advanced age (p = 0.017), myeloma subtype (p = 0.014), no prior chemotherapy (p = 0.012), and Len dosage (p = 0.008). Multivariate logistic regression analysis demonstrated that advanced age (≥ 70 years), BJP-subtype of myeloma and no prior chemotherapy were significant risk factors for the skin rash associated with Len. Thus, patients with these risk factors should be carefully monitored for the appearance of skin rash during the treatment with Len.

Determination of the concentration of gilteritinib in human plasma using HPLC.

Gilteritinib, an oral inhibitor of FMS-like tyrosine kinase 3 (FLT3), is a standard treatment for FLT3-mutated acute myeloid leukemia. We developed a simple HPLC-UV-based method for determining the concentration of gilteritinib in human plasma. The analysis requires the extraction of a 200-µL plasma sample and the precipitation of proteins by solid-phase extraction. Gilteritinib was isocratically separated within 10 min using a mobile phase of acetonitrile:0.5% monopotassium phosphate (KH2 PO4 , pH 3.5, 28:72, v/v) on a Capcell Pack C18 MG II (250 × 4.6 mm) column at a flow rate of 1.0 mL/min and monitored at 250 nm. The calibration curve was found to be linear within a plasma concentration range of 25-2500 ng/mL, with the coefficient of determination (r2 ) being 0.9997. The coefficients of intra-day and inter-day validation were 2.3-3.7 and 1.3-5.2%, respectively. The accuracy and recovery of the assay were -9.6 to 0.1 and >81.8%, respectively. This HPLC-UV method for determining the plasma concentration of gilteritinib is simple and can be effectively applied to routine drug monitoring.