Akio Okamoto

B‐cell lymphoma associated with haemophagocytic syndrome: a clinical, immunological and cytogenetic study

B‐cell lymphoma associated with haemophagocytic syndrome (HPS) is extremely rare in Western countries but has recently been increasingly reported in Asian countries. We describe seven patients with B‐cell lymphoma associated with HPS, six males and one female, age range 41–82 years (median 63 years). All patients had fever and splenomegaly, and six of the seven patients had hepatomegaly with no associated lymphadenopathy. The bone marrow showed haemophagocytosis and an infiltration of lymphoma cells. All patients showed increased levels of lactate dehydrogenase, C‐reactive protein, ferritin and soluble interleukin‐2 receptor. Lymphoma cells were positive for CD19, CD20 and surface immunoglobulin in all patients examined, and positive for CD5 in four of seven patients. Cytogenetic analyses of bone marrow cells showed a complex structural abnormality including chromosome 14q32 in two patients, 19q13 in three patients and deletion of the terminal part of 8p21 in six patients. The prognosis was poor; only two of the seven patients have survived in complete remission with a median survival of 11 months. These data suggested that B‐cell lymphoma associated with HPS might constitute a distinct biological and clinical disease entity. Abnormality of chromosome 19q13 and loss of 8p21 might be involved in the pathogenesis of this disease.

A newly developed bisphosphonate, YM529, is a potent apoptosis inducer of human myeloma cells.

We examined the effect of YM529, a newly developed third-generation bisphosphonate (BP), on the growth of human myeloma cell lines using the trypan blue dye exclusion test and Alamar blue assay. BPs induced inhibition of proliferation in all cell lines dose-dependently, and YM529 had a most potent growth inhibitory effect, followed by incadronate and pamidronate. Flow cytometric analysis using annexinV and 7AAD showed that YM529 most significantly induced apoptosis of all myeloma cell lines. These observations suggested that YM529 is a potent apoptosis inducer of myeloma cells, and might have some benefit not only on the improvement of bone lesions but also on survival in some myeloma patients.

Expression of T‐cell‐associated antigens in B‐cell non‐Hodgkin's lymphoma

We performed the immunophenotyping of 101 patients with B‐cell non‐Hodgkins lymphoma (B‐NHL) using two‐colour flow cytometry (FCM) and found that lymphoma cells coexpressed at least one kind of T‐cell‐associated antigen (T‐Ag; CD2, CD5, CD7) in 25 patients (24·8%). Among these three T‐Ags, CD5 was the most frequently expressed, in 21 patients (20·8%), followed by CD7, expressed in five patients (5·0%), and CD2, which was expressed in two patients (2·0%). Two kinds of T‐Ag were simultaneusly expressed in three patients (CD2/CD5, CD2/CD7, and CD5/CD7, each expressed in one patient). Concerning the expression pattern of T‐Ag, there were no significant differences between lymph nodes and extranodal organs in the three patients with T‐Ag‐positive B‐NHL (T‐Ag(+) B‐NHL) who were analysed. When comparing the clinical features between T‐Ag(+) B‐NHL and T‐Ag‐negative B‐NHL (T‐Ag(–) B‐NHL), extranodal involvement and higher International Prognostic Index (H and H.I.) were significantly frequent in the former subgroup (P = 0·0119 and P = 0·0302 respectively).

Successful peripheral blood stem cell transplantation for myelodysplastic syndrome

Wilms’ tumor (WT1) gene expression is increased in patients with leukemia as well as myelodysplastic syndrome (MDS) and is useful for detection of minimal residual disease (MRD). A 47-year-old man given a diagnosis of refractory anemia with excess of blasts in transformation (RAEB-T) received myeloablative therapy followed by autologous peripheral blood stem cell transplantation (PBSCT). MRD by WT1 expression was not detected in the graft. The patient has been in CR for 25 months after PBSCT. These observations suggest that PBSCT is feasible for patients with RAEB-T and analysis of WT1 expression can be applied for patients with high risk MDS.

Hyperleukocytosis in patients with leukemic follicular lymphoma

Dear Editor, Although about 10–35% of the patients with follicular lymphoma (FL) show the peripheral blood involvement (so-called leukemic change) at diagnosis, significant hyperleukocytosis more than 500×10/l seems quite rare [1, 2]. In this paper, we presented such two patients. Case 1 was a 56-year-old man who was admitted to the hospital because of facial edema, generalized lymph node swelling and hepatosplenomegaly. Laboratory findings were as follows: hemoglobin, 10.6 g/dl; platelets, 108×10/l; white blood cells, 560×10/l almost exclusively consisting of small lymphoid cells that showed the cleaved nuclei with high nuclear/cytoplasmic (N/C) ratio (Fig. 1a). Bone marrow was hypercellular with a significant number of such lymphoid cells. Serum lactate dehydrogenase (LDH) level was within normal range, whereas serum soluble interleukin-2 receptor (sIL-2R) level was elevated to 6,430 U/ml (normal range, 220–530 U/ml). Both cardiovascular and renal functions were well maintained. He was diagnosed as having FL grade 1 by cervical lymph node biopsy. Phenotypically, lymphoma cells were CD5, CD10, CD19, CD20, CD23, human leukocyte antigen -DR (HLA-DR) and IgG-κ. Cytogenetic analysis using Gbanding method showed the complex abnormality; 48, XY, der(8)t(8; 21)(p11; q11), t(14; 18)(q32; q21), +der(17)add (17)(p11), +dic(14; 18)(14pter→14q32::18q21→18pter), −18, +mar. He received the combined chemotherapies with/ without rituximab followed by autologous peripheral blood stem cell transplantation (ABSCT) resulting in complete remission. He had been alive for more than 4 years since the initial diagnosis so far. Case 2 was a 64-year-old woman who complained of abdominal fullness. She also showed the generalized lymph node swelling and hepatosplenomegaly. Laboratory findings were as follows: hemoglobin, 7.2 g/dl; platelets, 118×10/l; white blood cells, 516×10/l almost exclusively consisting of abnormal lymphoid cells as Case 1 (Fig. 1b). Bone marrow was hypercellular with a significant number of such lymphoid cells. Serum LDH level was 465 IU/l (normal range, 125–250 IU/l), and serum sIL-2R level was elevated to 12,000 U/ml. Both cardiovascular and renal functions were well maintained. She received the inguinal lymph node biopsy and was diagnosed as having FL grade 1. Phenotypically, lymphoma cells were CD5, CD10, CD19, CD20, CD23, HLADR and IgG-κ. Chromosomal analysis showed 46, XX, t(14; 18)(q32; q21). She received the combined chemotherapies with/without rituximab and obtained complete remission. She had been alive for more than 18 months since the initial diagnosis. Melo et al. [3] reported that patients with leukemic FL showing hyperleukocytosis more than 50×10/l at diagnoAnn Hematol (2007) 86:299–300 DOI 10.1007/s00277-006-0232-z

Early Relapse After High-Dose Chemotherapy Rescued by Tumor-Free Autologous Peripheral Blood Stem Cells in Acute Lymphoblastic Leukemia: Importance of Monitoring for WT1-mRNA Quantitatively

A 24-year-old woman who suffered from ALL with MLL gene rearrangement received high-dose chemotherapy followed by autologous PBSC transplantation during complete remission (CR). Reverse transcriptase-polymerase chain reaction (RT-PCR) used to detect MLL/LTG4 chimeric mRNA showed no minimal residual disease (MRD) in the graft or bone marrow at the transplantation. However, the leukemia relapsed four months after transplantation. Retrospective analysis of quantitative measurement of Wilms tumor gene (WT-1) mRNA showed an increased level in the bone marrow although it was within the normal range. These observations suggest that careful monitoring of MRD by quantitative measurement of WT-1 mRNA in addition to disease-specific chimeric mRNA is required to predict relapse.

The role of interleukin-6 in a patient with polyclonal hairy B-cell lymphoproliferative disorder: a case report.

An 80-year-old female patient showed persistent lymphocytosis morphologically resembling the Japanese variant of hairy cell leukemia (HCL). However, flow cytometric analysis determined that these lymphocytes were of polyclonal B-cell origin, showing CD5-, CD10(-), CD11c(+), CD19(+), CD20(+), CD23(-), CD103(-), FMC7(-), HLA-DR(+) and surface membrane immunoglobulin (smIg) G(+) phenotype. The female patient also showed polyclonal hypergammaglobulinemia with bone marrow plasmacytosis. The patient was diagnosed as having hairy B-cell lymphoproliferative disorder (HBLD). Serum interleukin-6 (IL-6) level was elevated at the time of diagnosis in this patient, but IL-6 receptor (CD126) was not expressed on the hairy B-cells. Intracellular IL-6 was not detected in these cells either, suggesting that IL-6 did not play an important role in the B-lymphocytosis present in our patient with HBLD.