Usage of granulocyte colony-stimulating factor every 2 days is clinically useful and cost-effective for febrile neutropenia during early courses of chemotherapy.

BACKGROUND: In order to analyze the clinical activity and cost-effectiveness of granulocyte colony-stimulating factors (G-CSF), the prophylactic usage of G-CSF in patients treated with a single chemotherapy regimen during early courses was prospectively evaluated. METHODS: Thirty patients with newly diagnosed non-Hodgkin lymphoma (NHL) treated with the first course of an R-CHOP regimen were enrolled randomly. After treatment with the first course of chemotherapy, a daily dose of G-CSF (lenograstim, 100 µg) was administered to half (15 cases) of the patients, and a dose of G-CSF (100 µg) was administered every other day to the other half of the patients when leukocytopenia (<1.5 × 10(9)/L) and/or neutropenia (<0.5 × 10(9)/L) occurred. Changes in leukocyte and neutrophil counts, prophylaxis, febrile neutropenia (FN) events, and cost performance between the two groups were analyzed. RESULTS: No significant difference between the two groups was observed in recoveries of leukocyte and neutrophil counts and evidence of FN. The only difference was the total cost of G-CSF. CONCLUSION: We concluded that every-other-day use of G-CSF was as clinically effective for the prophylaxis of FN as the daily use of G-CSF, and economically speaking, the administration of G-CSF every other day should be more beneficial for patients with NHL during early courses of R-CHOP chemotherapy.

Derivative (1;18)(q10;q10) in essential thrombocythemia.

This study reports the association of the chromosomal abnormality derivative (1;18)(q10;q10) with essential thrombocythemia (ET) occurring in a 75-year-old woman. Allele-specific polymerase chain reaction also revealed a V617F mutation in the Janus Kinase 2 gene (JAK2) in the platelet compartment in this patient. The der(1;18)(q10;q10) abnormality has previously been reported in two cases of myeloid disorders. The etiological implications for ET of this combination of chromosomal abnormality and JAK2 mutation still remain elusive. This is a novel report of derivative (1;18)(q10;q10) abnormality in ET.

[Acquired hemophilia complicated with multiple muscle abscess by Nocardia].

An 82-year-old man was referred to our hospital because of bilateral leg swelling and ecchymosis. A hemostatic study showed prolonged aPTT, <1% factor VIII coagulant activity, and a high titer (30.4 Bethesda Units/ml) of factor VIII inhibitor. The diagnosis of acquired hemophilia A (AHA) was made, and treatment with prednisolone (PSL) was started. Within one month of treatment, the hemorrhagic symptom disappeared, aPTT levels returned to normal, and his factor VIII inhibitor was eradicated; however, factor VIII inhibitor was detected again when PSL was decreased to 10 mg/day. We then added cyclosporine A (CyA) to PSL as a second line salvage therapy. CyA therapy resulted in the resolution of AHA with marked and prolonged efficacy; however, hot, red tumors appeared in his right arm and left thigh. Needle aspiration of the tumors revealed muscle abscess, and Nocardia brasiliensis was isolated. We started treatment with sulfamethoxazole-trimethoprim, and the abscess healed promptly without recurrence.

[Primary osseous lymphoma with pathological fracture during therapy].

A 66-year-old woman was aware of a cervical tumor in May 2007. She was hospitalized in June 2007 because her cervical tumor had increased. A biopsy was performed and a diagnosis of CD20-positive diffuse large B-cell lymphoma was obtained. Ga-67 scintigraphy showed abnormal accumulation in the right clavicle, right femur, right knee joint, right ankle joint, and the left tibia and fibula; however, no abnormality was detected on plain radiography and CT scan, whereas MRI showed that the right femur had a low signal on the T1-weighted image, and high and low signals on the T2-weighted image. CHOP therapy was begun, and the right cervical tumor promptly reduced. She was administered rituximab seven days after initiation of the treatment. When standing up from the toilet at midnight, she suffered fractures of the left tibia and fibula, and the right neck of the femur. These regions were identical to the sites with abnormal accumulation on Ga-67 scintigraphy, so we supposed them to be chemotherapy-associated pathologic fractures. This case is reported because primary bone lymphoma is rare and followed an unusual course of pathologic fracture under treatment.

Identification of an epitope derived from CML66, a novel tumor-associated antigen expressed broadly in human leukemia, recognized by human leukocyte antigen-A*2402-restricted cytotoxic T lymphocytes.

CML66 is a newly identified differentiation antigen that is expressed broadly in human leukemia and solid tumors, but its physiological function remains unknown. In the present study, to clarify the feasibility of CML66-targeted cancer immunotherapy, we attempted to identify cytotoxic T lymphocyte (CTL) epitopes derived from CML66. An immunogenic CML66-derived epitope (amino acid residues 76-84; YYIDTLGRI) capable of inducing human leukocyte antigen (HLA)-A*2402-restricted CTL specific for this peptide was identified. CML66-derived peptide-specific CTL efficiently lysed human leukemia cells, but not normal cells, in a HLA-A*2402-restricted fashion. Quantitative real-time polymerase chain reaction revealed that CML66 mRNA is expressed abundantly in primary acute myeloid leukemia cells, acute lymphoid leukemia cells, and chronic myelogenous leukemia cells in advanced phase, and that the expression level of CML66 mRNA in normal cells is low compared with that in leukemia cells. CML66-specific CTL precursors were detected in the peripheral blood of patients with acute leukemia. These data indicate that the CML66-derived epitope identified in the present study is a new target antigen for cellular immunotherapy of human leukemia.

Hypocellular acute promyelocytic leukemia with a tetraploid clone characterized by two t(15;17).

We describe a case of hypocellular acute promyelocytic leukemia with a tetraploid clone characterized by two t(15;17). The large leukemia cells had a bizarre nuclear configuration and multiple Auer rods. A bone marrow biopsy specimen revealed a markedly hypocellular marrow (<10% cellularity) in the absence of myelofibrosis. Myelodysplastic features were not detected. Chromosome analysis of marrow cells revealed a karyotype of 92,XXYY,del(2)(q?),t(15;17)(q22;q21)x2. Interphase fluorescence in situ hybridization revealed that the marrow cells were composed of a tetraploid clone carrying double t(15;17) and normal diploid cells. The leukemia responded well to all-trans retinoic acid. We think that the tetraploidy could be caused by endoreduplication or endomitosis of the diploid clone with single t(15;17). The unique karyotype largely contributed to the cell morphology and marrow hypoplasia, while it may not have affected on the prognosis of the acute promyelocytic leukemia.

Non-Hodgkin's lymphoma developing in a pacemaker pocket.

A 29-year-old man developed diffuse large B-cell lymphoma in a subpectoral pacemaker pocket that 6 years previously had been created in the chest for a titanium-covered pulse generator. The patient had an 8-cm-diameter dark red tumor with necrotic tissue on a keloidal surgical scar in the left side of the chest. Left axillary lymphadenopathy also was present. Laboratory studies showed an increased level of soluble interleukin 2 receptor and a normal level of lactose dehydrogenase. A biopsy specimen showed a diffuse large B-cell phenotype and monoclonal immunoglobulin H gene rearrangement. A gallium scintigraphy study showed abnormal accumulation in the left chest and left axilla. On the basis of these findings, we diagnosed diffuse large B-cell lymphoma, stage II. The patient received THP-COP chemotherapy (pirarubicin, cyclophosphamide, vincristine, and prednisolone) and radiotherapy, achieved complete remission, and was free of disease for 16 months after treatment. This case suggests that there was a relationship between the development of non-Hodgkin's lymphoma and the presence of chronic inflammation in the pulse generator pocket.

[Epstein-Barr virus-associated posttransplant lymphoproliferative disease after renal transplantation].

A 24-year-old Japanese male was admitted to our hospital because of lymphadenopathy in his left neck. He had a nine-year history of chronic renal failure, and had received an ABO-mismatched renal allograft and splenectomy in August 2000 after one year of hemodialysis treatment. After renal transplantation, he was treated with FK506, methylprednisolone (mPSL), and mycophenolate mofetil (MMF) as an immunosuppressants for his graft maintenance. On admission, April 2001, he underwent lymphadenectomy, and the immunohistochemical studies revealed that the tumor cells expressed EBV-LMP and EBNA-2 antigens with the histology of diffuse large B-cell lymphoma. Our diagnosis was an Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD), and we reduced the dose of immunosuppressive agents and treated the patient with rituximab. In this case, there may have been two principal risk factors associated with PTLD: first, the patient was treated with higher levels of immunosuppressive agents because of the ABO-mismatched transplantation, and second, he was an EBV-seronegative recipient at the time of pretransplantation.