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An 80-year-old Japanese man presented with systemic lymphadenopathy, including the para-aortic area and left inguinal nodes, which was diagnosed as diffuse large B-cell lymphoma (DLBCL) and human herpesvirus (HHV) 8-positive/HIV-negative Kaposi's sarcoma (KS). Immunohistochemical examination revealed that the lymphoma cells were negative for HHV-8. The patient received combined chemotherapy with rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone for six cycles and achieved complete remission. In the literature, five cases of simultaneous appearance of malignant lymphoma and KS in the same lymph node have been reported, but DLBCL as a histological subtype has not yet been reported.

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.

When the omicron variant became the most dominant severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) variant causing coronavirus disease 2019 (COVID-19) in Japan, 11 patients with hematological diseases infected with this new variant were treated at our institution. Among them, four of the five patients who had been treated with chemotherapy progressed to moderate-II COVID-19, and two of them died. In contrast, five of the six patients who did not receive the treatment remained at mild to moderate-I stage of COVID-19, except for a single case progressing to moderate-II COVID-19. While all four patients infused with anti-coronavirus monoclonal antibodies within 8 days after the onset survived, the other two patients, being withheld from treatment or treated later, died. In these two cases, anti-SARS-Cov-2 immunoglobulin G antibodies remained at low titers. Although the omicron variant is considered a less harmful SARS-Cov-2 variant, patients with hematological disorders, particularly those who are immunosuppressed caused by chemotherapy, should be continuously cared for as they remain at a higher risk of severe COVID-19 due to insufficient or delayed anti-viral humoral immunity development. Thus, the rapid introduction of antiviral monoclonal antibodies together with anti-viral reagents may rescue these patients.

An 80-year-old Japanese male patient presented to our hospital with complaints of fatigue. His peripheral blood tests revealed pancytopenia with predominant lymphocytes and without blasts. The bone marrow (BM) aspiration was unsuccessful due to a dry tap, and the subsequent BM biopsy revealed hypocellular marrow with fibrosis. He was diagnosed with myelodysplastic syndrome (MDS) with excess blasts (EB)-2 based on CD34-positive cells. The chromosome analysis of the BM revealed monosomy 7, and the SAMD9 W22 * mutation was detected (variant allele frequency [VAF] of 51.22%) using next-generation sequencing. An identical mutation was observed in the buccal mucosa (VAF of 50%), which was confirmed as a germline mutation. The SAMD9 gene mutation is reported as one of the causative genes for MIRAGE syndrome and child-onset MDS. The present case was considered a loss-of-function mutation due to the near full-length SAMD9 deletion. This is the first adult case of MDS with SAMD9 W22 * as a germline mutation.

An 83-year-old man was admitted to our hospital due to a recurrence of multiple myeloma, accompanied by the appearance of plasma cells in the peripheral blood (PB). Subsequently, he was diagnosed with secondary plasma cell leukemia (sPCL). A chemotherapy regimen of carfilzomib and dexamethasone (Cd) combination therapy was selected, and 15 days later, plasma cells completely disappeared from the PB. Cd therapy was continued, and the free kappa chain levels normalized. Three months later, M-protein could not be detected using serum electrophoresis. This is a valuable report wherein Cd combination therapy was successful in treating sPCL.

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.

A 62-year-old female patient was diagnosed with Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) 8 years ago, which was resolved with rituximab (R) monotherapy. Five years ago, she experienced numbness of the lower limbs, followed by diminished lower limb muscle strength and hearing disturbance. PET-CT scans showed accumulations along the peripheral nerves of the upper and lower limbs together with clonal B lymphocytes in the cerebrospinal fluid, thus a diagnosis of relapse with Bing-Neel syndrome (BNS). After a temporal remission by high-dose cytarabine or bendamustine plus R regimens as salvage treatments, WM/LPL recurred for the third time accompanied by gait disturbances due to muscle weakness and urinary retention. Thus, tirabrultinib was started as a subsequent therapy, which significantly improved the neurological condition together with abnormal findings of magnetic resonance imaging or cerebrospinal fluids. This case is valuable since few relapsed BNS was reported in the literature with successful tirabrutinib treatment.

From December 2019, a 71-year-old male underwent three cycles of a combination therapy of pomalidomide, bortezomib, and dexamethasone for relapsed multiple myeloma and a very good partial response was achieved. In March 2020, he developed a fever of 38.9°C and computed tomography revealed bilateral ground-glass opacities. Antibiotic therapy was ineffective. Bronchoscopy was performed and bortezomib-induced lung injury was initially suspected. Due to respiratory exacerbation, high-dose steroid therapy was administered, which resulted in a dramatic improvement of the patient's respiratory failure. Thereafter, reverse transcription polymerase chain reaction performed on a preserved bronchial lavage sample tested positive, and thus his diagnosis was corrected to COVID-19 pneumonia. It is difficult to discriminate COVID-19 pneumonia from drug-induced lung disease, as both disorders can present similar ground-glass opacities on computed tomography. Therefore, with this presented case, we summarize our experience with steroid therapy for COVID-19 associated respiratory distress at our institution.

PCR assay cannot always detect the SARS-CoV2 virus, which might be due to differences in the sensitivities of each sampling site. Under these circumstances, immunochromatography may serve as an alternative method to detect anti-SARS-CoV-2 IgG antibodies that can demonstrate a history of infection. In patients with severe COVID-19 infection, 14 of 19 serum samples were shown to be positive, whereas 6 of 10 samples from patients with asymptomatic or mild cases were negative for IgG antibodies. Two patients with immune thrombocytopenia, who were treated with prednisolone, experienced aggressive behavior of COVID-19-related respiratory failure and eventually died. Patients who were before an achievement of remission and those who received steroid-based chemotherapy possessed a higher risk of death, and more deaths were observed in patients with lymphoid malignancies including lymphoma and myeloma compared with those with myeloid malignancies. As for daily medical care in hematological department, a stricter cohorting strategy using repeat PCR tests or isolation to a private room should be adopted in order to prevent viral spread to the environment.

The Japanese Society of Hematology recently published on acute exacerbation of immune-mediated thrombocytopenia (ITP) after mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. In addition, there is a growing concern for the development of the newly diagnosed ITP after SARS-CoV-2 vaccination. Herein, we report two cases of severe thrombocytopenia associated with bleeding tendencies at 4 and 14 days after BNT162b2 mRNA vaccination. Platelet counts returned to normal following platelet transfusion or treatment with intravenous immunoglobulin and dexamethasone. To our knowledge at the time of the draft of this manuscript, nine cases of SARS-CoV-2 vaccine-induced ITP have been reported. Although most patients showed favorable clinical courses similar to that of our cases, critical thrombocytopenia can lead to unfavorable outcomes. A national survey may be required to examine the causal relationship between SARS-CoV-2 vaccination and the emergence of the newly diagnosed ITP and clinical outcomes of vaccine-induced thrombocytopenia.

We retrospectively evaluated the efficacy of pomalidomide/cyclophosphamide/dexamethasone (PCd) treatment in seven patients with extramedullary disease (EMD). Three of the seven patients achieved VGPR (very good partial response) with PCd therapy. We handled a patient complicated with secondary plasma cell leukemia, which was completely cured with PCd regimen and succeeded to autologous stem cell transplantation. In addition, there were no severe infections during the treatment period. This is the first report demonstrating the efficiency and tolerability of PCd treatment for EMD.

A 57-year-old Japanese man was referred to our hospital with the chief complaint of dizziness. Our investigations showed pancytopenia that necessitated bone marrow evaluation; this evaluation revealed plasma cell proliferation that was accompanied by numerous needle-shaped crystal inclusions. Clinical and laboratory examinations were used to establish a diagnosis of multiple myeloma (MM) accompanied by Fanconi syndrome. He was administered treatment with bortezomib, lenalidomide, or thalidomide; however, he died after experiencing upper abdominal pain of unknown etiology. Histopathological examination showed needle-like inclusions in the liver and kidney and macrophages in the bone marrow, suggesting light chain deposition disease (LCDD) that could contribute to multi-organ injury. We report the rare case of a patient with needle-shaped inclusions in MM that caused LCDD.

At our institution, an outbreak of hospital-acquired coronavirus infection (COVID-19) occurred in the hematology department. We used immunochromatography to examine the anti-COVID-19 IgG antibody level in 10 COVID-19 positive patients who exhibited little or no symptoms. Six patients were negative for IgG antibody at an average of 26 days (range: 11-39 days) after the COVID-19 diagnosis. Among them, two had been negative on PCR twice and were discharged but subsequently became positive on PCR 2-4 weeks later and developed pneumonia. These patients were also positive for IgG antibody after the confirmed diagnosis based on PCR accompanied with the development of pneumonia. Our findings suggest an immune response delay to COVID-19 in immunocompromised patients, such as those with hematologic disorders. Thus, follow-up examinations with antibody testing are important in these patients.

There have been many reports regarding tyrosine kinase inhibitor (TKI) administration to prevent relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). However, there are no commonly accepted standards for the choice of TKIs. We retrospectively analyzed the clinical features of Ph+ALL patients who received TKIs after allo-HSCT at our institution. The prophylactic administration of TKIs (pro) occurred in eight patients, and six patients received preemptive TKI administration (pre). The median follow-up period after allo-HSCT was 1,427 (range, 161-2,428) days in the pro group and 773.5 (range, 156-2,243) days in the pre group. Only one patient with non-hematological complete remission before allo-HSCT relapsed among the patients in the pro group. In the pre group, four patients treated with only TKIs achieved negativity of minimal residual disease. The 2-year overall survival rate after allo-HSCT was 85.7% in the pro group and 100% in the pre group. We used lower doses of TKIs compared with previous reports and this analysis shows that the dose is safe and effective as the treatment.

A 60-year-old man was admitted to our hospital with multiple organ failure complicated by disseminated intravascular coagulation. He presented with thrombocytopenia, pleural effusion, ascites, high fever, and renal impairment, suggesting TAFRO syndrome. In addition to administering prednisolone, dialysis and mechanical ventilation were initiated for severe renal and respiratory insufficiencies, respectively. However, he died 5 days after admission. An autopsy was performed, resulting in the diagnosis of human herpesvirus (HHV)-8-positive plasma cell-type Castleman's disease. Furthermore, HHV-8 was detected in the vascular endothelium and lymph nodes on immunohistochemical study. His rapidly deteriorating clinical course with the lack of serum hypergammaglobulinemia is atypical for Castleman's disease. Therefore, HHV-8 may have incited the disorder's aggressive behavior, causing TAFRO syndrome.

Nosocomial coronavirus disease 2019 (COVID-19) had occurred at our hospital. We retrospectively analyzed the differences between patients with nosocomial COVID-19 and either hematological disease (n=40) or other diseases (n=57). The analysis was completed within 60 days for surviving patients. Among the patients with hematological disease and those with other diseases, there were 21 (52.5%) and 20 (35.1%) deaths, respectively. Although the patients with hematological disease received favipiravir more frequently than patients with other diseases (21 [52.5%] vs. 15 [35.3%], respectively; P<0.05), their median overall survival was poor (29 days; P=0.078). Furthermore, the median duration from oxygen therapy initiation to death or intubation was significantly shorter in the patients with hematological disease (5 days [range, 1-17 days] vs. 10 days [1-24 days], respectively; P<0.05). Furthermore, the patients with hematological disease and nosocomial COVID-19 exhibited more marked respiratory failure and poorer outcomes leading to death in a shorter time period than the patients with other diseases and nosocomial COVID-19.

A 65-year-old male was admitted for bladder and rectal dysfunction with lower-limb sensory disturbance. Although no abnormalities were detected on magnetic resonance imaging of the brain and spinal cord, an elevation in the serum anti-cytomegalovirus (CMV) -IgM level and pneumonia suggest viral meningomyelitis. However, steroid pulse and anti-CMV treatments did not resolve the patients' symptoms. Lung and skin biopsies revealed an invasion of atypical lymphoid cells into small vessels, consistent with intravascular large B-cell lymphoma (IVLBCL). Chemotherapy comprising R-CHOP and intrathecal administration of methotrexate resolved neurological complications quickly, and the patient remains in complete remission after 2 years. Notably, IVLBCL with cauda equina syndrome is highly rare.

A 70-year-old female was initially diagnosed with acute myeloid leukemia (AML) and achieved complete remission by conventional chemotherapy. She presented with leukocytosis and pleural effusion six years later, and was diagnosed with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) by bone marrow (BM) analysis. Pyrexia and lymphadenopathy developed one year later, and lymph node biopsy confirmed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Chemotherapy achieved a partial remission. Fifty-two days after her last chemotherapy treatment, increased blasts in the peripheral blood along with marked lymphadenopathy were observed, which were considered to be indicative of the simultaneous development of AML and lymphoma. TET2 mutations were confirmed in BM and lymph node samples. Development of AML and PTCL-NOS might be due to clonal hematopoiesis associated with aging and chemotherapy.

A 71-year-old man diagnosed with IgG-κ type multiple myeloma 11 years ago was treated with low doses of pomalidomide (POM, 1 mg/daily) and dexamethasone (20 mg/week) as the third-line of salvage regimen. The treatment was terminated 4 days later owing to the appearance of a severe skin rash, which had also occurred after previous treatment with lenalidomide. After 2 months, POM was readministered via an outpatient desensitization protocol under prednisolone administration. During five cycles of POM-treatment, no severe skin rash appeared, and partial remission was obtained even though the final POM dose was as low as 1 mg/day.

We analyzed 95 cases of MDS (n=78), CMML (n=8) and AML (n=9) with blast counts of <30%, treated by AZA since March 2011, for a possible association of hematological improvement (HI) and overall survival duration (OS). We defined four categories as follows: stable disease (SD): no exacerbation of disease even if HI was not achieved after nine cycles of AZA treatment; early and late response (ER, LR): achievement of HI within and beyond three cycles, respectively; and drop out (DO): termination of treatment within nine cycles due to disease progression or complication without obtaining HI. OS was significantly longer in the LR than in the ER. The OS of ER was significantly shorter than that of the SD group. Patients in ER group who relapsed had significantly shorter survival than those who were able to maintain HI. Additionally, 3 out of 11 SD cases achieved HI after 10 cycles. We conclude that AZA should be continued until disease progression besides an achievement of HI.

Here we present a patient with rheumatoid arthritis (RA), who was suspected to have developed malignant lymphoma during immunosuppressive therapy 5 years earlier. She temporarily achieved remission after discontinuing therapy; however, her disease worsened with remittent fever and splenomegaly. Splenic biopsy demonstrated infiltration by abnormal cells, which were positive for CD56 and T cell intracytoplasmic antigen, but negative for CD3 and Epstein-Barr virus (EBV) -encoded RNA. Cytogenetic analysis of bone marrow and lumbar spine tumor revealed common complex karyotype abnormalities. Thus, she was diagnosed with chronic natural killer cell lymphoproliferative disorder (NK-LPD) and finally died of disease progression. The most common type of LPD in methotrexate-related patients with RA is B-lymphoid LPD, whereas NK-LPD is extremely rare. Furthermore, almost all cases of NK-LPD have been reported to be positive for EBV. This is the first case report on a patient with EBV-negative NK-LPD developed during immunosuppressive therapy for RA.

A 63-year-old man with Bence Jones-κ multiple myeloma (MM) presented with renal impairment. First, we administered a bortezomib-containing regimen which is considered to be the first choice among therapeutic approaches for MM patients with renal failure. However, his condition was refractory to bortezomib, and the renal dysfunction worsened (creatinine 12.55mg/dl) necessitating the initiation of hemodialysis. Subsequently, we administered an adjusted dose of lenalidomide and dexamethasone. Dialysis could be discontinued after 3 cycles of lenalidomide therapy. After 4 cycles, he achieved a stringent complete response (sCR) with the creatinine level at 1.85mg/dl. This case suggests lenalidomide to be an effective drug for patients with multiple myeloma and renal impairment refractory to treatment with bortezomib.

A medical check-up revealed severe anemia in an 85-year-old man who had been diagnosed with Waldenström macroglobulinemia 11 years previously. On the other hand, prolonged PT and aPTT were demonstrated on admission, and were attributed to a significant decrease in factor X activity. These abnormalities were all considered to be have been caused by an exacerbation of the underlying disease and, thus, chemotherapy with the RCD regimen (rituximab, cyclophosphamide, dexamethasone) was started. No significant improvement was obtained and the patient died suddenly on day 154. AL amyloidosis was diagnosed by histopathological examinations and also confirmed by a sequence analysis of amyloid protein. This case with Waldenström macroglobulinemia complicated by AL amyloidosis and recurrent factor X deficiency is quite rare.