Y. Hasegawa

Lymphomatous features of aggressive NK cell leukaemia/lymphoma with massive necrosis, haemophagocytosis and EB virus infection

Aims

Primary lymphoma arising in the nasal cavity among Japanese

Aims : Most lymphomas arising in the nasal cavity are thought to be of natural killer (NK) cell origin. However, some reports indicate that T‐ and B‐cell lymphomas may also primarily arise in the nasal cavity. We therefore studied lymphomas arising in the nasal cavity both histologically and immunohistochemically.

Effects of anti-platelet glycoprotein Ib and/or IIb/IIIa autoantibodies on the size of megakaryocytes in patients with immune thrombocytopenia.

Abstract: To determine whether anti‐platelet autoantibodies react with megakaryocytes, as well as with platelets, in immune thrombocytopenia (ITP), 38 ITP patients were studied. They were classified into four groups; anti‐platelet glycoprotein lb‐positive (group A, n> = 5), anti‐platelet glycoprotein II/b/IIIa‐positive (group B, n = 2), positive to both antibodies (group C, n = 3), and negative to both antibodies (group D, n = 28). The number and size of megakaryocytes in each group were compared. The number of megakaryocytes in groups A, B, C, and D was 12.8 ± 8.9, 75.2, 29.1, and 17.0 ± 21.7/mm2, respectively. The mean cytoplasmic area of megakaryocytes in groups A, B, C, and D was 1001 ± 26.3, 1621, 1109, and 1311 ± 235.6/μm2, respectively. This finding indicated that, in the presence of anti‐platelet glycoprotein Ib, megakaryocytes were not increased in number and were small in size, whereas, in the presence of anti‐platelet glycoprotein Ilb/IIIa, megakaryocytes were increased in number and in cytoplasmic area. Our study suggested that anti‐platelet glycoprotein Ib may impair platelet production by megakaryocytes in ITP.

Aprepitant does not alter prednisolone pharmacokinetics in patients treated with R-CHOP

Aprepitant, a neurokinin 1 receptor antagonist, is an effective antiemetic drug in the prevention of chemotherapy-induced nausea and vomiting. Aprepitant co-administration increases plasma concentrations of dexamethasone and methylprednisolone by inhibiting cytochrome P450 (CYP) 3A4 [1], whereas pharmacokinetics of cyclophosphamide, which is also metabolized by CYP enzymes including CYP3A4, is not significantly changed by aprepitant [2]. Thus, aprepitant co-administration provides different effects on pharmacokinetics of CYP substrates; however, it is unknown whether aprepitant affects pharmacokinetics of prednisolone, another CYP3A4 substrate. We aimed to evaluate the effect of aprepitant on pharmacokinetics of prednisolone, and the safety and efficacy of aprepitant when administered together with rituximab, cyclophosphamide (Shionogi, Osaka, Japan), doxorubicin (Adriamycin) (Sandoz, Tokyo, Japan), vincristine (Nippon Kayaku, Tokyo, Japan), and prednisolone (R-CHOP) in patients with non-Hodgkin’s lymphoma. We conducted a nonrandomized, open-label, single-group before/after design study between courses 1 and 2 of R-CHOP. This study was approved by the institutional review board of the University of Tsukuba Hospital. Patients received 100 mg of oral prednisolone from days 1–5 in divided doses of 60 mg at 8 am and 40 mg at 1 pm. Aprepitant was added orally for 3 days (125 mg on day 1, and 80 mg on days 2 and 3) at 7 am during the course 2. In each course, 3 mg of granisetron was given twice on day 1. Ten patients (diffuse large B-cell lymphoma in seven and follicular lymphoma in three) completed the study. Antiemetic CR (defined as no emetic episodes and no use of rescue medication) without and with aprepitant was observed in 8 and 10 out of 10 patients, respectively. A series of serum prednisolone concentrations in eight patients were measured. The mean AUC of prednisolone from 0 to 5 h was not different between the courses 1 and 2 (2200 ± 490 and 2178 ± 794 ng h/ml, respectively; P = 0.932) (Figure 1), although areas under the curve of prednisolone were increased in four patients and decreased in other four patients by the co-administration of aprepitant. The median (range) Tmax [2 (0.5–2) and 2 (0.5–5) h, respectively] and the mean Cmax (646 ± 191 and 634 ± 285 ng/ml, respectively; P = 0.88) were not affected by aprepitant. There was no significant difference in blood glucose concentration and blood pressure level between the courses 1 and 2. Previous studies have shown that CYP3A4 inhibitors, such as ketoconazole and itraconazole, do not affect the metabolism of prednisolone [3, 4], whereas they increase plasma concentration of dexamethasone and methylprednisolone [1]. Consistent with these reports, our results indicated that aprepitant had virtually no impact on prednisolone pharmacokinetics. Hepatic metabolism for prednisolone is different from those for dexamethasone and methylprednisolone, in that 11-β-hydroxysteroid dehydrogenase plays a role in addition to CYP3A4 only for prednisolone, through the conversion of the hydroxyl group to ketone on the 11th position of C-ring. Therefore, the contribution of CYP3A4 to the metabolism may be lower in prednisolone than in dexamethasone and methylprednisolone [5]. We concluded that aprepitant could be safely administered when strengthened antiemetic treatment is required, without serious drug interactions with prednisolone in R-CHOP.

Hodgkin Disease with Subsequent Transformation to CD30 Positive Non-Hodgkin Lymphoma in Six Patients

Previous studies have indicated that some patients with Hodgkin disease have an aggressive clinical course. However, their characteristics have not been elucidated.

Shortened lifespan of paroxysmal nocturnal haemoglobinuria-affected RBC estimated from differences in ratios of CD59-negative populations between reticulocytes and whole RBC.

Paroxysmal nocturnal haemoglobinuria (PNH) is a haemolytic disease characterized by complement‐sensitive red blood cells (RBC). PNH‐affected RBC (PNH‐RBC) should have a shortened mean lifespan (MLS); however, direct measurement is difficult. We have recently developed a sensitive flow cytometric assay to analyse PNH‐affected reticulocytes that may closely correspond to the PNH clone‐derived erythropoiesis. Naturally, the CD59‐negative populations in reticulocytes were larger than those in whole RBC in PNH. We estimated the MLS of PNH‐RBC in six PNH patients from the differences in the ratios of CD59‐negative populations between reticulocytes and whole RBC. The MLS of PNH‐RBC was calculated using the following formula: W/100 = R × M/[(100 − R) × 120 + R × M], where W, percentage CD59‐negative whole RBC; R, percentage CD59‐negative reticulocytes; M, MLS (days) of CD59‐negative RBC. The MLS of PNH‐RBC, estimated as 16–45 days in the PNH patients, showed a weak positive and a weak negative relation with RBCs and percentage reticulocytes, respectively, among the patients. The MLS, in individual patients, altered irrespective of RBC and percentage reticulocytes. The MLS calculated from our methods may be a parameter that evaluates the haemolytic conditions in PNH.

Non-Hodgkin's lymphoma followed by plasmacytoma, both arising in A thyroid gland with Hashimoto's disease.

We describe here a rare case of malignant lymphoma followed by plasmacytoma in Hashimotos thyroiditis. The patient developed malignant lymphoma (small, non-cleaved cell, and non Burkitts type by Working Formulation classification), and remained in remission for 2 years after receiving combination chemotherapy, and then developed plasmacytoma in the same lesion. Rearrangement bands for IgH from both specimens showed different bands, indicating that both were of monoclonal type but of a different clonal origin. Considering the clinical course in this case, thyroidectomy may be indicated for lymphoproliferative diseases in Hashimotos thyroiditis treated with chemotherapy.

Priming effects of macrophage colony-stimulating factor on monocytic leukemia cells in combination with chemotherapy: induction of programmed cell death in vivo.

Two elderly patients with chronic myelomonocytic leukemia were treated with cytosine ara-binoside (Ara-C) and aclarubicin (ACR) under simultaneous administrations of macrophage colony-stimulating factor (M-CSF) (CAM), and both obtained good responses. Examination of apoptosis using flow cytometry revealed induction of apoptotic death of leukemia cells by CAM in Patient 2, while neither induction of apoptotic death of leukemia cells nor clinical response were seen with CAG (Ara-C, ACR, and granulocyte colony-stimulating factor) given prior to CAM in Patient 1. These findings suggested that chemotherapy combined with simultaneous administration of M-CSF could effectively reduce monocytic leukemia cells by inducing programmed cell death.