A Radical Approach to Acute Lymphoblastic Leukemia Treatment: A Case Study of a Veterinarian Specializing in Livestock who Developed Disseminated Mucormycosis during Induction Therapy.

Mucormycosis has emerged as the third-most common fungal mycosis and is one of the most fatal molds. We herein report a case study of a 30-year-old woman who was a veterinarian, specializing in livestock, who developed disseminated mucormycosis during induction therapy for acute lymphoblastic leukemia. We successfully used a radical approach for treatment, including a surgical procedure and allogeneic transplantation, with continuous administration of antifungal agents. Reports of successful treatments are extremely rare, and our case has had the longest documented remission from disseminated disease. We speculate that our case's occupational environment may represent a risk factor for development of mucormycosis.

[Philadelphia chromosome-positive acute lymphoblastic leukemia with basophilic blast features].

A 62-year-old man was referred to our hospital due to pancytopenia and abnormal leukocyte fraction in December 2016. Bone marrow aspiration showed a massive proliferation of blast cells (96%) with rich myeloperoxidase-negative basophilic granules. He was diagnosed with acute basophilic leukemia, and an appropriate treatment for acute myelogenous leukemia was initiated. Blast cells were positive for minor BCR-ABL mutations, and chemotherapy using imatinib was initiated on day 7. The treatment was effective and complete remission was achieved on day 30. The ultrastructural features of blast cells showed typical basophilic granules with high electron density structure on electron microscopy. However, immunohistochemical analysis were positive for CD79a, PAX5, and TdT expression. Rearrangements of immunoglobulin heavy chain and T-cell receptor genes were detected, prompting the diagnosis of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) with basophilic change. The patient continued to be treated with the imatinib combination regimen, as well as umbilical cord blood transplantation. The patient has currently achieved recurrence-free survival. This case represents a rare divergence between morphology and molecular condition.

Development of AML without karyotype abnormalities including the Ph chromosome in a CML patient on second-generation TKI therapy.

A 58-year-old man was diagnosed with accelerated phase chronic myelogenous leukemia (CML). He was treated with dasatinib and followed-up; 6 months later, he achieved a complete molecular response. Seventeen months after this therapy, he developed pancytopenia, and was examined. His diagnosis was Ph-negative acute myeloid leukemia (AML) with no karyotype abnormalities. He was administered two courses of induction chemotherapy, and during the first remission, he received allogeneic hematopoietic stem cell transplantation. Treatment with a tyrosine kinase inhibitor (TKI) achieved a successful outcome. However, approximately 10% of CML cases develop clonal cytogenetic changes in Ph-negative cells during TKI treatment, and rarely, cases of Ph-negative myelodysplastic syndrome or AML are reported. Furthermore, similar to our case, CML patients developing AML with Ph-negative and normal chromosome abnormalities have been reported. We suggest vigilant monitoring during TKI therapy and stress the importance of further analysis based on similar accumulated cases.

A phase II trial of small-dose bortezomib, lenalidomide and dexamethasone (sVRD) as consolidation/maintenance therapy in patients with multiple myeloma.

PURPOSE: Consolidation/maintenance therapy induces deep remission in patients with multiple myeloma (MM); however, the most suitable regimen has been under investigation. The combination therapy with bortezomib, lenalidomide and dexamethasone (VRD) is a powerful regimen for relapsed/refractory as well as newly diagnosed MM as an induction therapy. However, severe adverse events (AEs) may become a problem when VRD is introduced without dose reduction as a consolidation/maintenance therapy. METHODS: In this single-arm phase II study, we evaluated the efficacy of small-dose VRD regimen (sVRD) in the consolidation/maintenance setting. Sixteen patients who had partial response (PR) or better after any induction therapy were enrolled. Patients received at least six 28-day cycles of subcutaneous bortezomib (1.3 mg/m2 on days 1 and 15), lenalidomide (10 mg on days 1-21) and dexamethasone (40 mg on days 1, 8, 15 and 22). RESULTS: The overall response rate and the complete response (CR) rate were 100 and 43.8 %, respectively. In particular, one patient with CR and two patients with very good PR at enrollment achieved stringent CR during 6 courses of sVRD. With a median follow-up time of 29.4 months, the median progression-free survival (PFS) and overall survival (OS) were not reached, while the PFS and OS rates at 2.5 years were 66.6 and 77.3 %, respectively. Univariate analysis demonstrated that disease progression as a reason for discontinuation of sVRD had a negative impact on OS. There were no grade 3 or 4 hematologic or nonhematologic AEs. CONCLUSION: Our sVRD regimen as a consolidation/maintenance therapy was highly effective and well tolerable.

Effect of duloxetine in Japanese patients with chemotherapy-induced peripheral neuropathy: a pilot randomized trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is difficult to manage. A phase III trial conducted in the United States demonstrated that duloxetine was effective for CIPN caused by taxane and platinum-based chemotherapy. No randomized trial of duloxetine for CIPN has been conducted in Japan. METHODS: In this open-label, randomized, crossover study, eligible patients were randomized to Group A or Group B. Group A received duloxetine 20 mg/day orally for the first week and 40 mg/day for the next 3 weeks. Group B received vitamin B12 (VB12) 1.5 mg/day orally for 4 weeks. After a 2- to 4-week washout period, treatment was crossed over for another 4 weeks. The severity of numbness and pain was assessed using a visual analog scale (VAS). RESULTS: Thirty-four patients were enrolled. Obvious decreases in the mean VAS scores for numbness and pain were observed for the periods of duloxetine administration. Significant differences were observed between the duloxetine-first (Group A) and the VB12-first (Group B) groups with respect to numbness (p = 0.03) and pain (p = 0.04) at 4 weeks after administration. Fatigue was observed in six of the 34 participants (17.6 %). CONCLUSIONS: Our data suggests that duloxetine has a beneficial effect on CIPN caused by oxaliplatin, paclitaxel, vincristine, or bortezomib in Japanese patients.

A role for peripherally inserted central venous catheters in the prevention of catheter-related blood stream infections in patients with hematological malignancies.

Central venous catheter-related blood stream infections (CR-BSIs) are a serious complication in patients with hematological malignancies. However, it remains unclear whether there is a difference in the rate of CR-BSI associated with the conventional type of central venous catheters (cCVCs) and peripherally inserted CVCs (PICCs) in such patients. To address this question, we retrospectively investigated the incidence of CR-BSIs associated with PICCs versus cCVCs in patients with hematological malignancies. We used PICCs in all consecutive patients requiring CVC placement between February 2009 and February 2013. We compared the CR-BSI rate in patients with PICCs with that in patients with cCVCs treated between September 2006 and January 2009 (control group). Eighty-four patients received PICCs and 85 received cCVCs. The most common reason for removal due to catheter-related complications was CR-BSI. The CR-BSI rate in the PICC group was significantly lower than that in the cCVC group (PICCs: 1.23/1000 catheter days; cCVCs: 5.30/1000 catheter days; P < 0.01). Catheter-related complications other than CR-BSIs occurred at an extremely low rate in the PICC group. The median catheter-related complication-free survival duration was significantly longer in the PICC group than in the cCVC group. Our study shows that PICCs are useful in patients with hematological malignancies.

Late onset neutropenia and immunoglobulin suppression of the patients with malignant lymphoma following autologous stem cell transplantation with rituximab.

BACKGROUND: Recently, decrease of immunoglobulin concentrations or neutrophil counts were reported in some cases several months after administration of rituximab. We examined a number of episodes of late onset neutropenia or immunoglobulin decrease in patients with malignant lymphoma who were in complete remission following autologous transplantation with or without rituximab. METHOD: Patients with follicular lymphoma and diffuse large B cell lymphoma transplanted with or without rituximab in our institutes were analyzed. Immunoglobulin concentrations and neutrophil counts after transplantation, both with and without rituximab were measured serially. RESULTS: Four weeks after transplantation, blood samples revealed lower concentrations of IgG and IgA in the rituximab group than in the non-rituximab group. Neutrophil numbers did not fall below 0.5x10(9) /L four weeks or more after transplantation in the non-rituximab group. Neutrophil numbers dropped below 0.5x10(9) /L in 6 of 14 cases in the rituximab group. CONCLUSION: Although the present study was retrospective and disease composition and pre-transplantation regimens differed between the two groups, the addition of rituximab to autologous transplantation might bring about a decrease of immunoglobulin levels and transient LON.

[De novo CD5-positive diffuse large B-cell lymphoma associated with autoimmune hemolytic anemia presenting as erythroid hypoplasia].

A 54-year-old woman was admitted due to high-grade fever, cervical lymphadenopathy and general malaise in May 2003. On examination, severe anemia was noted, direct Coombs and cold hemagglutinin tests were positive and the haptoglobin level was low in the peripheral blood. However, a bone marrow examination revealed marked erythroid hypoplasia. A diagnosis was made of co-existing combined type autoimmune hemolytic anemia (AIHA) and erythroid hypoplasia. A pathologic diagnosis of de novo CD5-positive diffuse large B-cell lymphoma (de novo CD5+ DLBCL) was made based on a cervical lymph node biopsy. The patient was treated with CHOP accompanied by rituximab (R-CHOP), resulting in complete remission after 3 courses of chemotherapy. The AIHA and erythroid hypoplasia subsided after 2 courses of R-CHOP. The sera obtained during erythroid hypoplasia significantly inhibited the growth of erythroid progenitor cells (erythroid colony-forming units, CFU-E) from her bone marrow collected after recovery. We report here a patient with de novo CD5+ DLBCL associated with both AIHA and erythroid hypoplasia, suggesting that the lymphoma triggered an abnormal immunity which generated some humoral inhibitors against erythropoiesis.

[Effective combined modality therapy for a patient with primary adrenal lymphoma].

Primary adrenal lymphoma is a rare lymphoma with clinical features consisting of a high incidence of bilateral adrenal involvement, diffuse large B-cell histology and secondary adrenal insufficiency. We report a successful treatment of a patient with primary adrenal lymphoma using a combined modality therapy (CMT). A 62-year-old man was hospitalized with pain of the flank, and a computed tomography (CT) scan of the abdomen revealed very large, bilateral adrenal masses. A needle biopsy of the left adrenal mass revealed diffuse large B-cell lymphoma. After irradiation of both adrenal lymphomas and CHOP therapy accompanied by intrathecal treatment and rituximab, the patient underwent a left adrenalectomy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation. The patient has been disease-free for 2 years after the diagnosis of primary adrenal lymphoma. In contrast to the previous reports of poor response to conventional-dose chemotherapy alone and short-term survival of patients with primary adrenal lymphoma, our patient has demonstrated that radiation therapy combined with chemotherapy and rituximab may be an effective modality as a first-line therapeutic regimen for localized primary adrenal lymphoma.