Yasunori Kawachi

Acute arterial thrombosis due to platelet aggregation in a patient receiving granulocyte colony-stimulating factor

We describe a 44‐year‐old man with non‐Hodgkins lymphoma receiving granulocyte colony‐stimulating factor (G‐CSF) who developed an acute arterial thrombosis. The removed thrombus contained large amounts of platelet aggregation. A rapid increase of platelets and increased adenosine diphosphate (ADP)‐ and collagen‐induced platelet aggregation were observed at the time of the thrombotic event. A challenge test of G‐CSF showed an increase in the platelet count and an augmentation of ADP‐ and collagen‐induced platelet aggregation. In the use of G‐CSF, patients who produce a rapid increase in platelet levels could be at greater risk for thrombotic events and need to be followed‐up carefully.

Long-term remission in HIV-negative patients with multicentric Castleman's disease using rituximab.

Abstract:  Multicentric Castlemans disease (MCD) is an indolent lymphoproliferative disorder. The pathogenesis of MCD has not been established, and its treatment remains uncertain. Several authors have described the relationship of human herpes virus type 8 (HHV‐8) to MCD in human immunodeficiency virus (HIV)‐positive patients. Recently, anti‐CD20 monoclonal antibody (rituximab) is increasingly being used to treat HIV‐positive MCD; although it is uncertain whether rituximab is effective for HIV‐negative patients with MCD. To explore the benefit of rituximab for HIV‐negative patients with MCD, we describe the clinical and biologic course in three HIV‐negative patients with MCD, and examined the relationship of HHV‐8 infection to HIV‐negative MCD. Their polymerase chain reaction analyses for the HHV‐8 sequence in peripheral blood were negative, and there was no relationship between HHV‐8 infection and symptoms of HIV‐negative MCD. Two of three patients (66%) achieved a near complete remission with no clinical symptoms due to MCD with a follow‐up of 16–40 months after rituximab administration. One of the three patients presented no clinical remission of MCD after rituximab administration, although a significant decrease of inflammatory parameters was observed. These findings suggest that rituximab treatment may be an appropriate first‐line therapy for HIV‐negative MCD.

Successful treatment of multicentric Castleman's disease with bilateral orbital tumour using rituximab.

thalidomide from 200 mg to the maximum-tolerated dose was used in 12 patients with AL amyloidosis. The median maximum-tolerated dose was 500 mg; four patients discontinued the drug as a result of side-effects (worsening congestive cardiac failure, dyspnoea, renal dysfunction). However, it was continued beyond the 6-month trial period in three patients who derived some benefit from the drug. In our patient, as the thalidomide was used as part of a combination chemotherapy, we were able to use a lower dose and did not escalate the dose during the treatment period. We have used this combination chemotherapy (C-ThaD) successfully in the setting of relapsed and refractory myeloma. The oral regime Z-Dex was ineffective in this case, the patient deteriorating rapidly while receiving that treatment. The C-ThaD regime was introduced as it had an intravenous component without requiring a central line, in addition to the combination of thalidomide and pulsed dexamethasone. We conclude that this novel combination regime may be an effective alternative treatment for patients with AL amyloidosis, where the treatment can be tolerated.

Adult T‐cell leukaemia/lymphoma featuring a large granular lymphocyte leukaemia morphologically

Summary A 70‐year‐old man from an endemic area of human T‐cell lymphotropic virus type I (HTLV‐I) developed rapid generalized lymphadenopathy and abdominal tumours. The white blood cell count was 198·3%× 109/l with 93% lymphocytes, 66·3% of which expressed large granular lymphocytes (LGLs). Bone marrow and lymph nodes were also infiltrated by LGLs. Surface markers were positive for CD4, CD25 and HLA‐DR, and negative for CD3, CD8, CD16, CD56 and CD57. A monoclonal integration of HTLV‐I proviral DNA was demonstrated on these LGLs by Southern blot hybridization analysis. This fact indicates that some adult T‐cell leukaemia/lymphoma may morphologically present LGL leukaemia.

Watershed infarction associated with dementia and cerebral atrophy.

A 63‐year‐old man was admitted with progressive left hemiparesis and left homonymous hemianopsia of 1 month’s duration. During the 2 months before admission, he had suffered from slowly progressive dementia. The diagnosis of right‐sided watershed (WS) infarction was made. He exhibited slow progression of dementia and cerebral atrophy during the period of observation after discharge. There was a positive relationship between cerebral atrophy and the degree of dementia. In the present case, WS infarction caused by right internal carotid artery occlusion might be related to dementia and cerebral atrophy.

Extra Y chromosome in T-cell acute lymphoblastic leukemia

We describe a 66-year-old man who developed T-cell acute lymphoblastic leukemia (ALL) with a sole clonal chromosomal abnormality of 47,XY,+Y. Leukemic cells were positive for CD2, CD7, terminal deoxynucleotidyl transferase and cytoplasmic CD3. T-cell receptor beta, gamma, and delta genes remained germline configurations. The bone marrow aspirate was 47,XY,+Y in all metaphase cells observed. The patient achieved complete remission by chemotherapy, and the bone marrow cells and the phytohemagglutinin stimulated peripheral blood lymphocytes showed a normal karyotype of 46,XY at that time. This fact suggests that an extra Y chromosome may be a kind of new chromosomal abnormality of T-cell ALL.

Richter's Syndrome Showing Pronounced Lymphadenopathy in Response to Administration of Granulocyte Colony-Stimulating Factor

A patient with Richters syndrome developed rapid generalized lymph node enlargement with a decrease of peripheral blood lymphocytes after recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy for neutropenia induced by chemotherapy. The lymphadenopathy subsided spontaneously following discontinuation of rhG-CSF medication. Reinstitution of rhG-CSF therapy was followed by the same response as during initial therapy. Histopathologically, the lesions were characteristic of diffuse large cell lymphoma (DLL) with no evidence of myeloid cell involvement. No spontaneous contraction of enlarged lymph nodes followed withdrawal of the second course, but the enlargement subsided with chemotherapy. The patient died of myocardial infarction. All residual tumors examined post mortem presented microscopic features of small lymphocytic lymphoma (SLL), and G-CSF receptor was demonstrated on these neoplastic cells by Northern blot hybridization analysis. This observation indicates that some B cell malignancies may retain G-CSF receptor and respond to G-CSF.

KAPOSI'S SARCOMA ASSOCIATED WITH ADULT T‐CELL LEUKAEMIA

Pharm. Co., Tokyo, Japan) was started. Neutrophils began to increase in April. In a n effort to improve anaemia, therapy with rhEpo (Chugai Pharm. Co., Tokyo, Japan) was started from July. Hb and P1,T began to increase in October. In January 1991 his blood cell counts attained the normal range, and bone marrow was normocellular with normal haemopoietic elements. However, cessation of rhG-CSF and rhEpo resulted in progressive decrease in blood cells as well as bone marrow cellularity. To restore haematopoiesis, administration of rhG-CSF and rhEpo was resumed from March 199 1, resulting in once again trilineage recovery. Case I . A 1 7-year-old man was referred to hospital because of general malaise in September 1990. Laboratory tests revealed an H b of 3 . 6 g/dl, cRET 0.03%). W13C 2 . 3 x 10y/l with 1 O(%, neutrophils, PLT 8 x 1 Oy/l , and serum Epo 4 1 0 0 nilJ/ml. Bone marrow was extremely hypocellular and depleted of megakaryocytes. From these findings. he was diagnosed as having SAA (Camitta et (

Burkitt type leukaemia associated with multiple myeloma

1, 1979) with unknown aetiology. Since he lacked HLA-matchcd siblings, combination therapy with rhG-CSF and rhEpo was started from October 1YYO (Fig lb). The trilineage recovery was achieved in September 1991. It is possible that ALG played a main role in the trilineage recovery in Case 1 since the effectiveness of ALG had been reported (Champlin et al, 1983). However, his recovery was completely dependent on rhC-CSF and rhEpo. The dependency of hacmopoiesis on rhG-CSF and rhEpo makes it unlikely that the patient achieved a spontaneous recovery unrelated to the treatment, and also rather suggests that the recovery was due not to A I G but to rhC-CSF and rhEpo. The clinical course of Case 2 also supports this hypothesis although dependency on the cytokines is not demonstrated. The mechanism by which rhGCSF and rhEpo induced the recovery of thrombopoiesis is unclear, but G-CSF is reported to enhance the proliferation of haemopoietic stem cells (Tkebuchi ct t r l . 1988) and Epo is reported to stimulate thrombopoiesis in v i t ro (Vainchenker ~t t r l , 1979). Combination therapy of rhG-CSF and rhEpo may be a therapeutic option in AA without HLA-identical siblings.

Acute Myeloblasts Leukemia Associated with an Intermediate State Between the Healthy Carrier State and Adult T-cell Leukemia

We describe a 77‐year‐old man with multiple myeloma (MM) who developed Burkitt type leukaemia (BTL) 16 months after the initial diagnosis of MM. MM was positive for CD10 with immunoglobulin (Ig) κ, κ, Bence Jones protein (BJP) and a normal karyotype. BTL was positive for CD10, CD19, CD20 and HLA‐DR with Ig μ and γ, γBJP and a clonal abnormal karyotype of 46, XY, ‐13, t(8;14)(q24;q32), 11q+,14q+, +mar. The patient died 9 d after diagnosis of BTL despite treatment with multiple agents. This is, to our knowledge, the first such case to be reported.