Intermediate-dose cyclophosphamide and bortezomib for PBSC mobilization in multiple myeloma.

Although the incorporation of bortezomib into induction regimens has improved response rates in patients with multiple myeloma (MM), the role of bortezomib in the peripheral blood stem cell (PBSC) mobilization remains unclear. We assessed the PBSC mobilization efficacy, safety, and disease response of intermediate-dose cyclophosphamide and bortezomib in the PBSC mobilization. Twenty-one patients with newly diagnosed MM were enrolled in a phase II, non-randomized study that used bortezomib (1.3 mg/m2/day on days 1, 4, 8, and 11) and intermediate-dose cyclophosphamide (2 g/m2/day on days 2, 3) (Bor-ID-CY). The data from 15 patients who received intermediate-dose cyclophosphamide (ID-CY) were used as a historical control group. The total CD34 + cell yield of Bor-ID-CY and ID-CY groups were not significantly different (median 6.3 ×106/kg vs. 6.5 ×106/kg, p = 0.26). All three patients with mobilization failure of two groups had t(11;14). Six patients in Bor-ID-CY group were upgraded from a status that was less than a very good partial response (VGPR) at the time of PBSC mobilization to a VGPR or better after PBSC mobilization (p = 0.014). Four patients in Bor-ID-CY group developed sepsis. The time to engraftment was similar in the two groups. The addition of bortezomib to ID-CY did not impact the stem cell yield or quality.

A case of prolonged COVID-19 treated with tixagevimab/cilgavimab.

A 54-year-old woman presented to our hospital with a fever and cough. The patient had a medical history of follicular lymphoma treated with obinutuzumab. She was infected with an omicron variant of coronavirus disease 2019 and developed viral pneumonia. Antibiotics, molnupiravir, sotrovimab, and prednisolone were administered but were ineffective. The patient's symptoms and pneumonia persisted. She could not produce antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because she was administered obinutuzumab. Finally, when we administered 300 mg of tixagevimab and cilgavimab, pneumonia immediately improved. However, the infection was prolonged for more than 4 months. Patients treated with anti-CD20 monoclonal antibodies may have a prolonged SARS-CoV-2 infection. In such cases, tixagevimab/cilgavimab may be effective.

[Ultra high-risk refractory multiple myeloma with a complex karyotype including t(14;19)].

A 78-year-old man was hospitalized because of rapid progression of chronic renal failure and diagnosed with multiple myeloma (MM) IgG-λ type ISS-III R-ISS-II with complex karyotype including t(14;19). Even after receiving bortezomib-based regimens, his renal failure progressed. He became dependent on dialysis, which was required three times a week. After introducing the daratumumab (DARA)-based regimen, his renal function improved, the frequency of dialysis decreased to twice a week, and the free light chain (FLC) ratio also improved. However, his myeloma eventually followed a refractory course; therefore, pomalidomide (POM)-dexamethasone (Pd) regimen was administered. Pd regimen had a marked effect and normalized the FLC ratio after three courses of the treatment. However, his myeloma reprogressed with multiple extramedullary masses and he became del(17p) positive; eventually, he died on the 470th day of disease. MM with t(14;19) is rare and has a poor prognosis with a highly aggressive course; however, early introduction of DARA or POM may provide long-term response.

Efficacy of upfront high-dose chemotherapy plus rituximab followed by autologous peripheral blood stem cell transplantation for untreated high-intermediate-, and high-risk diffuse large B-cell lymphoma: a multicenter prospective phase II study (JSCT-NHL04).

To evaluate the efficacy and feasibility of upfront high-dose chemotherapy (HDCT) and rituximab (R) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) in patients with newly diagnosed high-intermediate(HI)-, and high(H)-risk diffuse large B-cell lymphoma (DLBCL), we conducted a multicenter prospective phase II trial. In 15-60-year-old patients with H- or HI-risk DLBCL, after three courses of (R-)CHOP14, high-dose etoposide was given prior to peripheral blood stem cell harvesting. After an additional three courses of (R-)CHOP14, auto-PBSCT was performed following HDCT. The primary endpoint of the study is progression-free survival (PFS) at 2 years after registration in eligible patients. The expected PFS and the threshold PFS were estimated to be 70 and 50 %, respectively. Among 40 eligible patients registered, 30 patients completed treatment. With a median observation period in surviving eligible patients of 63 months, the 2- and 4-year PFS after registration were 79.9 and 72.0 %, respectively. The 2- and 4-year overall survival (OS) were 92.5 and 84.6 %, respectively. In 30 patients who completed treatment, the 4-year PFS and OS after auto-PBSCT were 79.2 and 85.9 %, respectively. In conclusion, the results of our study suggest that upfront HDCT and auto-PBSCT combined with rituximab is highly effective as an initial treatment for HI-, and H-risk DLBCL.

Efficacy and safety of micafungin as an empirical therapy for invasive fungal infections in patients with hematologic disorders: a multicenter, prospective study.

This study was conducted as a prospective, multicenter trial to evaluate the efficacy and safety of micafungin as an empirical therapy for suspected invasive fungal infections (IFIs), including febrile neutropenia (FN), and to evaluate the usefulness of ß-D: -glucan (BG) and Aspergillus galactomannan (GM) antigen in patients with hematologic diseases. A total of 121 patients were enrolled and assessed for safety, and 119 were examined for clinical efficacy. The main underlying diseases were acute myeloid leukemia (38.0%), acute lymphoblastic leukemia (18.2%), and malignant lymphoma (18.2%). The median initial daily dose and duration of micafungin treatment were 150 mg/day and 13 days, respectively. The overall response rate for suspected IFIs (n = 119), based on four composite endpoints, including baseline IFI, breakthrough IFIs (proven and probable), survival, and premature discontinuation, was 79.0%. In addition, the response rate for FN (n = 81), based on these four endpoints as well as defervescence during neutropenia, was 39.5%. Breakthrough IFIs (proven, probable, and possible) occurred in five patients during micafungin treatment. All of these patients were positive for either BG or GM before the breakthrough IFIs. The incidence of adverse events (AEs) associated with micafungin was 10.7% and most were mild. The majority of AEs were liver dysfunction. These results indicate the effectiveness and safety of micafungin as an empirical therapy for suspected IFIs, including FN, and the usefulness of monitoring both BG and GM to detect breakthrough IFIs.

Ischemic heart disease associated with bortezomib treatment combined with dexamethasone in a patient with multiple myeloma.

A 79-year-old female patient with multiple myeloma who had no prior cardiac disease history developed an acute myocardial infarction on day 5 after receiving bortezomib and dexamethasone (BD). After treatment of coronary stenoses by stents, she received another course of BD therapy and developed angina pectoris on day 5 after the therapy. Bortezomib's antitumor effect is due to the inhibition of proteasome activity. This inhibition may increase endothelial progenitor cell apoptosis and decrease endothelial nitric oxide synthase/nitric oxide (eNOS/NO), thus leading to coronary spasm. It is, therefore, important to carefully monitor patients being treated with bortezomib for the potential occurrence of ischemic heart disease.

A case of retroperitoneal and mediastinal fibrosis exhibiting elevated levels of IgG4 in the absence of sclerosing pancreatitis (autoimmune pancreatitis).

There is now increasing evidence that IgG4 is closely involved in idiopathic sclerosing lesions, such as sclerosing pancreatitis and sclerosing sialadenitis. In this report, we describe a case of IgG4-related retroperitoneal and mediastinal fibroses. A 52-year-old man presented with dull back pain and was found to have a continuously surrounding paraaortic mass. A biopsy specimen taken from the retroperitoneum showed a diffuse lymphoplasmacytic infiltration intermixed with fibrosis. Many IgG4-positive plasma cells were demonstrated on immunostaining. His serum IgG4 concentration was 392 mg/dL (reference range, <70). We treated this patient with a corticosteroid, which markedly diminished the paraaortic mass along with lowering of his serum IgG4 concentration. The possible involvement of IgG4 was suggested in the pathogeneses of retroperitoneal and mediastinal fibroses in this patient. IgG4 might be useful in the clinical management of retroperitoneal or mediastinal fibrosis to differentiate them from malignant tumors and predict steroid sensitivity.