[A case of intestinal myiasis in a bedridden elderly patient].

A 75-year-old man with type 2 diabetes and a history of previous empyema surgery was admitted to our hospital due to difficulty moving caused by chronic obstructive pulmonary disease and dehydration. During the first two days of hospitalization, intestinal myiasis was diagnosed after maggots were found in his diapers. After the maggots disappeared, he developed a fever, prompting antibiotic therapy for a suspected secondary infection, resulting in clinical improvement. Despite thorough home cleaning, no flies or maggots were found, and the source of infection and the fly species remained unknown. Recent reports suggest a higher prevalence of myiasis among the elderly, even with overall improvement in hygiene. While myiasis is typically mild, it is a condition that requires consideration in an aging society. Myiasis is a disease that should be considered in the differential diagnosis of the elderly, especially in people who are bedridden or frail.

Type 1 diabetes mellitus after cord blood transplantation from an unrelated donor with a disease-sensitive haplotype.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a curative treatment for hematopoietic neoplasms, often causes various autoimmune disease-like conditions. In contrast, allo-HSCT-related type 1 diabetes mellitus is extremely rare. Herein, we report a case of allo-HSCT-related type 1 diabetes mellitus in a patient who had undergone cord blood transplantation (CBT) as a treatment for acute myeloid leukemia. The patient's human leukocyte antigen was replaced with the donor type after transplantation. The donor had a disease-sensitive haplotype. To the best of our knowledge, this is the first reported case of type 1 diabetes mellitus following CBT.

Serum high-density lipoprotein cholesterol level has a significant prognostic impact on outcomes of follicular lymphoma patients.

We investigated the potential of nutritional and inflammatory parameters as prognostic factors for follicular lymphoma (FL), and also examined the predictive value of the early progression of disease within 24 months of first-line chemo-immunotherapy (POD24). We retrospectively analyzed 46 patients with FL admitted to Teikyo University Hospital and treated with chemo-immunotherapy between May 2009 and July 2019. Physical characteristics, blood parameters, and markers or scores for consumptive/inflammatory and nutritional conditions were used as variables. Nine parameters correlated with poor overall survival (OS) in univariate analysis: An Eastern Cooperative Oncology Group (ECOG) scale performance status (PS) ≥2, five or more involved nodal sites, positive bone marrow (BM) involvement, a serum albumin level <3.5 g/dL, CRP >0.5 mg/dL, lactate dehydrogenase (LD) higher than the upper normal limit (UNL), high-density lipoprotein cholesterol (HDL-C) <40 mg/dL, modified Glasgow prognostic score of 1-2, and the geriatric nutritional risk index <82. In multivariate analysis, ECOG PS ≥2, positive BM involvement, and a serum HDL-C level <40 mg/dL remained significant for poor progression-free survival. One-year OS rate after receiving salvage chemotherapy was lower in the POD24 group (50%) and POD24 correlated with ECOG PS ≥2, positive BM involvement, a serum lactate dehydrogenase >UNL, and HDL-C <40 mg/dL by Fisher's exact test. These results indicate that low serum HDL-C levels appear to be important for predicting the risk of POD24 and the worse prognosis of FL.

The FLT3 internal tandem duplication mutation at disease diagnosis is a negative prognostic factor in myelodysplastic syndrome patients.

The role of the FMS-like tyrosine kinase 3 (FLT3) gene in acute myeloid leukemia (AML) has been well documented and the FLT3-internal tandem duplication (FLT3-ITD) mutation has been identified as a prognostic factor in AML. Due to its low incidence, the role of the FLT3 mutation remains unclear in myelodysplastic syndrome (MDS) patients. To investigate the impact of the FLT3-ITD status on the prognosis of MDS at diagnosis, we retrospectively analyzed 72 MDS patients admitted to Teikyo University Hospital. FLT3-ITD was examined by a reverse transcription-polymerase chain reaction using complementary DNA synthesized from mRNA extracted from bone marrow mononuclear cells at the diagnosis of MDS. Fifteen patients (20.8 %) were positive for FLT3-ITD and had significantly worse overall survival (OS) and progression-free survival (PFS) than patients who were negative (P < 0.001 and P < 0.001, respectively) in a multivariate analysis. We also investigated whether the Wilms' tumor gene-1 (WT-1) copy number was associated with the FLT3-ITD mutational status using data available on WT-1 from 57 patients. A WT-1 transcript copy number ≥50/µg total mRNA in peripheral blood was detected in 35 patients (61.4 %). All FLT3-ITD-positive patients showed WT-1 ≥50. The FLT3-ITD-positive group showed significantly higher WT-1 transcription levels than the negative group. These results indicate that the FLT3-ITD mutation has a prognostic impact at the diagnosis of MDS and is associated with a high level of WT-1.

Bilateral nephromegaly due to direct leukemic cell invasion in the initial and relapse phases of T-cell acute lymphoblastic leukaemia: A case report.

RATIONALE: T-cell acute lymphoblastic leukemia is a relatively uncommon disorder in adults. Kidneys are not frequently invaded by leukemic cells, and patients with adult ALL showing nephromegaly as an initial presentation are rare. PATIENT CONCERNS: A 54-year-old man was referred to our institution for mild anemia and thrombocytopenia. Laboratory tests showed bicytopenia with abnormal lymphoid cells in the peripheral blood and mild renal dysfunction. DIAGNOSIS: Ultrasonography and computed tomography (CT) revealed bilateral enlargement of the kidneys. [18F]-fluorodeoxyglucose positron emission tomography/CT demonstrated a strong increase in metabolic uptake in the bilateral kidneys. A kidney biopsy revealed a leukemia invasion into the parenchyma. Based on the lymphocytic repertoire, the patient's condition was diagnosed as T-cell acute lymphoblastic leukaemia. INTERVENTIONS: The patient received hyper-cyclophosphamide, vincristine, adriamycin, and dexamethasone and high-dose methotrexate and cytarabine as induction chemotherapy. After his leukemia relapsed, he received nelarabine as a second induction therapy and underwent haploidentical peripheral blood stem cell transplantation. OUTCOMES: Complete remission (CR) was achieved after chemotherapy. Chemotherapy also improved renal function associated with the normalization of bilateral nephromegaly. Repeated [18F]-fluorodeoxyglucose - positron emission tomography/CT posttreatment showedregression of metabolic uptake in the bilateral kidneys. The patient underwent cord blood transplantation at the first CR, but his leukemia relapsed 9 months later. At relapse, bilateral nephromegaly reappeared. Then, the second induction therapy induced CR for at least 10 months after induction therapy. LESSONS: Although rare, ALL in the initial and relapsed phases can be associated with bilateral nephromegaly and renal impairment due to the invasion of leukemic cells into the parenchyma with or without abnormal leukemic cells in circulation. Leukemia is an important differential diagnosis of renal impairment with bilateral nephromegaly.

Second allogeneic transplantation using umbilical cord blood for a patient with relapsed ALK+ anaplastic large cell lymphoma after allogeneic bone marrow transplantation in the era of ALK inhibitors: A case report.

RATIONALE: Anaplastic lymphoma kinase (ALK) + anaplastic large cell lymphoma (ALCL) is considered as a good prognosis lymphoma. However, in an extremely rare subset of patients, ALK+ ALCL with leukemic presentations is known to be chemotherapy-resistant. Although several novel therapies have been tested, the standard therapy for relapsed/refractory ALK+ ALCL has not been established yet. PATIENT CONCERNS: An 18-year-old female patient who had conventional chemotherapy- and Brentuximab Vedotin (BV)-resistant ALK+ ALCL with leukemic presentation. She was successfully treated with an ALK inhibitor, crizotinib. Crizotinib induced complete remission (CR) and bridged to allogeneic bone marrow transplantation (BMT). DIAGNOSIS: However, her ALCL relapsed on day 60 after BMT and she developed high grade fever and lymphadenopathy. INTERVENTION: Although crizotinib was given to the patient immediately after relapse, she developed grade 3 nausea and could not continue to take it. Then, we gave alectinib to the patient, which promptly induced sustained CR without any further chemotherapy. The patient received second stem cell transplantation using umbilical cord blood with myeloablative regimen in 2nd CR. OUTCOMES: The patient has been in CR under maintenance therapy of alectinib for more than 16 months. LESSONS: Both ALK inhibitors demonstrated drastic efficacy for our patient who had chemotherapy- and BV-resistant ALK+ ALCL with leukemic presentation. Alectinib showed less gastro-intestinal toxicity than crizotinib and the patient was able to take it even at the relatively early phase of stem cell transplantation.

Functional expression cloning of molecules inducing CD34 expression in bone marrow-derived stromal myofibroblasts.

We have previously shown a fraction of stromal fibroblasts/myofibroblasts (Fibs) from leukemic bone marrow cells expresses leukemia-specific transcripts along with hematopoietic and Fib-related markers. Normal bone marrow-derived Fibs (nFibs) do not express CD34 or CD45; however, nFibs may express hematopoietic markers with some specific stimulations. CD34 expression was detected in nFib cultures following the addition of a culture supernatant of blood mononuclear cells stimulated with phytohemagglutinin (PHA)-P. To identify the molecules responsible for inducing CD34 expression in nFibs, cDNA clones were isolated using functional expression cloning with a library constructed from PHA-P-stimulated human blood mononuclear cells. Positive clones inducing CD34 transcription in nFibs were selected. We confirmed that an isolated positive cDNA clone encoded human interleukin (IL)-1 beta (ß). CD34 expression was observed in the nFib cultures with recombinant human (rh) IL-1ß protein. And CD34 transcription was suppressed when a rhIL-1ß neutralizing antibody was added to the IL-1ß-stimulated nFib cultures. nFibs expressed gp130 and IL-6 receptors, and CD45 expression was detected in nFibs cultured with rhIL-1ß and rhIL-6. Chronic myelogenous leukemia (CML) cells reportedly respond well to IL-1ß. When CML-derived Fibs were cultured with rhIL-1ß and rhIL-6, CD45-positive cells increased in number. Cell fate may be influenced by an external specific stimulation without gene introduction.

Gemtuzumab ozogamicin monotherapy prior to stem cell infusion induces sustained remission in a relapsed acute myeloid leukemia patient after allogeneic stem cell transplantation: A case report.

RATIONALE: Patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have poor prognosis. Many patients are not eligible for 2nd HSCT due to organ dysfunction or other complications that prevent them from tolerating conditioning chemotherapy. In those ineligible patients for 2nd HSCT with myeloablative conditioning regimen, reduced intensity conditioning (RIC) are often used. RIC regimens are less toxic but has a less direct anti-tumor efficacy so that RIC regimens are not suitable for the patients with high tumor burden. To overcome this dilemma, Gemtuzumab Ozogamicin (GO) has been used as a part of RIC regimens to add anti-tumor efficacy. We report here a relapsed AML patient who was treated with GO monotherapy followed by stem cell infusion. PATIENT CONCERNS: A 25-year-old male with AML experienced relapse 9 months after allo-HSCT. DIAGNOSIS: Since he had mild renal and cardiac dysfunction and his AML did not progress rapidly, we decided not to give him an intensive chemotherapy. However, after azacitidine (AZA) and donor lymphocyte infusion therapy, his leukemic blasts did not decrease. INTERVENTIONS: Originally, we had planned to proceed with a 2nd allo-HSCT with RIC regimen that consisted of fludarabine, melphalan and fractionated GO (3 mg/m/dose) on day -21, -18, and -15. However, the patient developed appendicitis after the last dose of GO when his neutrophil was 0 cells/µl. Based on his medical acuity, we terminated the rest of the patients conditioning regimen and the patient did not receive any further chemotherapeutics. The patient was still infused with peripheral blood stem cells from the donor on day 0. OUTCOMES: His appendicitis was resolved by antibiotics without surgery. His AML has been in CR more than 18 months under AZA maintenance therapy. LESSONS: GO monotherapy could be a conditioning regimen of 2nd allo HSCT from the same donor as the first HSCT for relapsed AML patients.