[HLA-haploidentical peripheral blood stem cell transplantation with post-transplantation cyclophosphamide for adult T-cell leukemia].

Recently, allogeneic peripheral blood stem cell transplantation from human leukocyte antigen (HLA)-haploidentical donors using post-transplantation cyclophosphamide (PTCY-haploPBSCT) has become available in clinical practice. However, the efficacy of PTCY in adult T-cell leukemia (ATL) is not fully established yet. In this study, we retrospectively examined data of seven patients who underwent PTCY-haploPBSCT. The overall survival rate at 100 days after transplantation was 85.7%, and the 1-year overall survival rate was 68.6%. The cumulative incidence of relapse at 1 year was 31.4%, whereas the 1-year nonrelapse mortality was 17.1%. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) on day 100 was 14.3%, and the incidence of chronic GVHD at 1 year was 33.3%. These results suggest that PTCY-haploPBSCT can be a viable option even in patients with ATL. Further accumulation of knowledge and improvement of transplantation outcomes are warranted in the future.

Alterations in Cisplatin Pharmacokinetics and Its Acute/Sub-chronic Kidney Injury over Multiple Cycles of Cisplatin Treatment in Rats.

Cisplatin (CDDP)-induced acute kidney injury (AKI) is a major clinical concern. CDDP treatment is generally conducted with multiple cycles; the magnitude of the CDDP-induced AKI may be altered by these cycles. Moreover, sub-chronic kidney injury (sCKI) induced by repeated CDDP treatment is often associated with renal interstitial fibrosis, potentially leading to chronic kidney disease. Therefore, it is suggested that the management of not only AKI but also sCKI induced by CDDP in multiple cycles plays an important role in the outcome of CDDP-based chemotherapy. This study investigated the alteration in pharmacokinetics and toxicodynamics of CDDP that was repeatedly administered for three cycles in rats; a cycle consisted of CDDP (5.0 mg/kg, bolus injection) followed by a 21-d washout period. AKI and sCKI were evaluated by plasma creatinine concentration. In repeated multiple administration of CDDP, renal clearance was decreased and the amounts of accumulated Pt in kidneys increased by the cycle. AKI and sCKI were similarly exacerbated by the cycle, whereas the degree of AKI showed a large inter- and intra-individual variation in each cycle. However, the degree of sCKI constantly increased (creatinine increasing ratio in any cycle is about 150%), suggesting that the degree of sCKI in any given cycle was predictable by monitoring the initial creatinine baseline. In this study, therefore, it is suggested that the evaluation of sCKI by monitoring creatinine concentration at base is important for the estimation of CDDP-induced nephrotoxicity. These results may provide useful information for more effective and safe CDDP-based chemotherapy with evidence-based dose adjustment.

Intracranial Myeloid Sarcoma Mimicking Hypertensive Intracerebral Hemorrhage.

We herein report a case of intracranial myeloid sarcoma mimicking hypertensive intracerebral hemorrhage. A 71-year-old man with a history of acute myeloid leukemia was admitted with acute-onset dysarthria. A hematoma-like lesion was found on computed tomography in the left putamen. Magnetic resonance imaging (MRI) and cerebrospinal fluid cytology confirmed the diagnosis of intracranial myeloid sarcoma. The patient showed a favorable response to chemotherapy, and follow-up MRI revealed shrinkage of the tumor. Since the computed tomography findings resemble those of intracerebral hemorrhage, it is important to suspect intracranial neoplasm, particularly in cases with a history of hematologic diseases.

Diffuse Large B-cell Lymphoma Involving an Abundant Infiltration of T Follicular Helper Cells.

A 76-year-old man presented with skin plaque and splenic nodules, and diffuse large B-cell lymphoma (DLBCL) with infiltration of T-cells was suspected based on the skin lesions. The disease showed indolent clinical behavior for three months, when systemic lymphadenopathy rapidly evolved. An inguinal lymph node biopsy revealed DLBCL with abundant infiltration of T follicular helper (TFH) cells. A polymerase chain reaction-based analysis of immunoglobulin variable heavy chain showed that the skin, splenic nodules, and inguinal lymph node shared the same clone. This case indicates that the dysregulated infiltration of TFH cells in the tumor microenvironment accelerates the lymphomagenesis and progression of DLBCL.

Type II Cryoglobulinemic Membranoproliferative Glomerulonephritis Caused by Mucosa-associated Lymphoid Tissue Lymphoma.

A 67-year-old man complained of lower limb edema with a purpuric skin rash. Laboratory tests revealed proteinuria, elevated serum creatinine levels, and low serum albumin levels. The patient was also positive for cryoglobulin in serum, immunoglobulin (Ig) M gammopathy, hypocomplementemia, and rheumatoid factor. He was negative for anti-hepatitis C virus antibodies. A pathological analysis of the renal tissue revealed membranoproliferative glomerulonephritis, common histological features of cryoglobulinemic vasculitis (CV), and mucosa-associated lymphoid tissue lymphoma invasion. Although hematologic malignancy is a rare cause of type II CV, these clinical findings suggest that mucosa-associated lymphoid tissue lymphoma (MALT) lymphoma may have been the cause in the present case.

Immune Thrombocytopenia Exacerbation After COVID-19 Vaccination in a Young Woman.

The coronavirus disease 2019 (COVID-19) pandemic is one of the greatest health concerns worldwide. Safe and effective COVID-19 vaccines are urgently needed and have been rapidly approved. COVID-19 vaccine-induced thrombocytopenia was reported as a rare adverse effect in the Vaccine Adverse Events Reporting System. A 25-year-old woman, who was previously diagnosed with immune thrombocytopenia (ITP, stage I), had exacerbated severe thrombocytopenia (platelet count of 6,000/µL) with a headache, joint pain, general fatigue, and bleeding tendency three days after receiving her second dose of the Pfizer BioNTech COVID-19 vaccine. Pulsed high-dose dexamethasone therapy rapidly ameliorated the ITP. Although it is difficult to confirm a causal association between Pfizer BioNTech COVID-19 vaccination and ITP exacerbation, abrupt onset of ITP exacerbation after vaccination suggests that the ITP may be vaccination-induced thrombocytopenia exacerbation. Rare but severe adverse events such as ITP may be observed, depending on increased numbers of individuals who receive COVID-19 vaccines worldwide. Further investigation is needed to clarify the mechanisms of COVID-19 vaccine-induced ITP.

Accelerated Phase of Atypical Chronic Myeloid Leukemia with Severe Disseminated Intravascular Coagulation at Initial Presentation.

Patients with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) are often asymptomatic and thus can remain undiagnosed until they become symptomatic due to progression to the accelerated phase (AP) or transformation to acute leukemia (leukemic transformation; LT). We herein report the case of a previously healthy 38-year-old man who had hyperleukocytosis with dysplastic myeloid precursor cells and severe disseminated intravascular coagulation. Hematopoietic recovery with features of atypical chronic myeloid leukemia (aCML) after induction chemotherapy was a diagnostic clue. Although rare, this case highlights the limitation of the diagnostic approach for aCML with AP or LT at the initial presentation.

Remarkable synergies between baicalein and tetracycline, and baicalein and beta-lactams against methicillin-resistant Staphylococcus aureus.

During the screening of compounds that potentiate the effect of antimicrobial agents against methicillin-resistant Staphylococcus aureus(MRSA), we found that an extract of thyme (Thymus vulgaris L) leaves greatly reduced the minimum inhibitory concentration (MIC) of tetracycline against MRSA. We isolated the effective compound and identified it as baicalein (5, 6, 7-trihydroxyflavone). One of the clinically isolated MRSA strains possessed tetK, a gene encoding active efflux pump for tetracycline. We examined the effect of baicalein on the efflux of tetracycline, using Escherichia coli KAM32/pTZ1252 carrying the tetK. The E. coli KAM32/pTZ1252 showed 8 to 16 times higher MIC than E. coli KAM32. We observed strong inhibition of transport of tetracycline by baicalein with membrane vesicles prepared from E. coli KAM32/pTZ1252. Baicalein also showed synergy with tetracycline in a MRSA strain that doesn't possess tetK, or with beta-lactams. Thus, mechanisms of the synergies seem to be versatile.