[Acute monoblastic leukemia with tetrasomy 8].

Tetrasomy 8 is a rare chromosomal abnormality in acute leukemia, and it has recently been considered as a poor prognostic factor. A 20-year-old woman was admitted because of purpura on the upper and lower limbs in February 2002. On admission, her leukocyte count was 6.5 x 10(9)/l with 66% of blasts, the hemoglobin level was 11.2 g/dl, and the platelet count was 101 x 10(9)/l. The bone marrow aspirate contained 85.6% of peroxidase-negative, alpha-naphthyl-butyrate esterase-positive, and CD4+ CD56+ blast cells. Karyotypic analysis of the bone marrow cells showed 48, XY, + 8, + 8[17]/47, XY, +8[3]. The patient was diagnosed as having AML (M5a), and treatment with daunorubicin (70 mg x 5 days) and cytosine arabinoside (150 mg x 7 days) resulted in a complete remission. She relapsed four months later, however, with an extramedullary tumor in T12. Remission could not be achieved, and the patient underwent allogeneic peripheral blood stem cell transplantation from her HLA-identical mother. Her clinical course was almost uneventful except for a phlegmon in the right leg, but on day 49 a relapse occurred, and she died of acute renal failure on day 73. This case strongly illustrates the characteristic of tetrasomy 8 as a poor prognostic factor in acute leukemia.

CD56 positive intestinal T-cell lymphoma: treatment with high dose chemotherapy and autologous peripheral blood stem cell transplantation.

A 63-year-old man presented with a perforation of the small intestine. A diagnosis of intestinal T-cell lymphoma (ITCL) was made from CD (cluster differentiation) 3 positivity and a rearrangement of T-cell receptor genes. The tumor also expressed CD56, which suggests it belongs to a rare subtype derived from activated cytotoxic intraepithelial T lymphocytes. Although the prognosis of ITCL has been considered to be very poor irrespective of CD56 positivity, complete remission was achieved in this case by high dose chemotherapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) even after relapse. Auto-PBSCT in the earlier stage of the disease might improve the prognosis.

[Abscopal effect of small intestinal NK/T-cell lymphoma].

The abscopal effect is characterized by the spontaneous regression of unirradiated tumors resulting from the effect of irradiation on remote tissue. We report a case of NK/T-cell lymphoma of the small intestine that achieved complete remission as a result of an abscopal effect. A 74-year-old Japanese woman was referred to our hospital because of ileus and suspected perforation of the gastrointestinal tract. An emergency operation was performed and a perforated ulcerative tumor in the small intestine and enlarged mesenteric lymph nodes were found. Histopathological examination of the resected small bowel showed infiltration of large lymphoid cells with irregular nuclei and they were positive for CD3, CD56, TIA-1 and granzyme B. Physical examination did not reveal any lymphadenopathy in the neck, axillary or inguinal regions, skin involvement or nasal infiltration. The CT scans revealed multiple tumors in her upper abdomen and an obstructing conglomerate of small intestinal tumors. The patient did not show any response to CHOP therapy and radiotherapy was delivered to the lower abdominal field for the treatment of the ileus at a total dose of 44 Gy. Two months after radiotherapy, abdominal CT scans showed the disappearance of not only the tumors in the irradiation field but also the upper abdominal tumors that had not been irradiated. The patient has remained in complete remission for 15 months.

[Non-myeloablative stem cell transplantation from an HLA identical sibling donor in a case of treatment-related acute myelogenous leukemia].

A 50-year-old man was admitted to our hospital because of thrombocytopenia during a follow up study of diffuse large B-cell lymphoma in second complete remission. He was diagnosed as having therapy-related acute myelgenous leukemia (t-AML) on the basis of the bone marrow findings and his chemotherapeutic agent history including alkylating agents. Complete remission was achieved by induction chemotherapy. Although allogeneic stem cell transplantation was thought to be needed, the patient was thought to be ineligible for any myeloablative conditioning regimen because of his age and the history of long term chemoradiotherapy. A non-myeloblative regimen was thus selected. After preconditioning with fludarabine, cyclophosphamide and cytarabine, the patient underwent peripheral blood stem cell transplantation from an HLA identical sibling donor. Complete donor chimeras were obtained on day 28 after transplantation. Regimen related toxicities over grade 2 were not observed. Although he suffered from mild chronic graft-versus-host disease(GVHD), he is in good condition without any signs of relapse during a follow-up period of 33 months. It is suggested that non-myeloablative transplantation is feasible and benefical for patients with t-AML who are often ineligible for myeloablative transplants because of their histories of long term chemoradiotherapies.

A retrospective analysis of bortezomib therapy for Japanese patients with relapsed or refractory multiple myeloma: beta2-microglobulin associated with time to progression.

Bortezomib is approved for the treatment of patients with relapsed or refractory multiple myeloma (MM), but only a few clinical studies for Japanese patients who were treated with bortezomib have been reported. We retrospectively analyzed 40 patients with relapsed or refractory MM who have received bortezomib at three collaborating centers in Miyagi prefecture in Japan. All the patients have been received bortezomib in combination with dexamethasone. Responses were determined using International Myeloma Working Group uniform response criteria. The overall response was observed in 30 patients (75%), including very good partial response in 8 patients (20%), and partial response in 22 patients (55%). The median time to disease progression was 8.7 months, and the median overall survival has not been reached. The factors affecting time to disease progression were International Staging System stage, serum beta2-microglobulin level, and number of treatment cycles. The most common grade 3 and 4 adverse events were thrombocytopenia (50%), peripheral neuropathy (25%), leukopenia (25%), and herpes zoster infection (25%). Thus, bortezomib is well tolerated and effective for Japanese patients with relapsed or refractory MM. Our results suggest that serum beta2-microglobulin level may be a marker of prognosis on bortezomib therapy for patients with relapsed or refractory MM although further studies are needed.

Predictive value of the original content of CD34(+) cells for enrichment of hematopoietic progenitor cells from bone marrow harvests by the apheresis procedure.

We retrospectively investigated the feasibility of the apheresis procedure for red blood cell (RBC) reduction with a closed-bag system. We also sought to determine the optimal processing volume for the maximal recovery of hematopoietic progenitor cells (HPC). Twelve bone marrow (BM) harvests were processed for major ABO-incompatible allogeneic transplantation and one BM harvest was processed for autologous transplantation. The processing was performed through seven apheresis cycles with a two-bag system using COBE Spectra Version 6.1. The mean recovery rates were compared in the products after four cycles and seven cycles of BM processing. Mean cell recovery rates were 79.2% (67.6-97.5%) and 87.3% (68.9-111.9%) for the mononuclear cells (MNC) and 84.5% (69.4-109.5%) and 92.0% (79.0-107.7%) for the CD34(+) cells after four and seven cycles, respectively. A mean of 96.3% (93.0-98.1%) of the RBCs were finally removed. The yield of CD34(+) cells after seven cycles of processing (median: 10.35 x 10(7) cells) was 7.9% greater than that after four cycles of processing (median: 9.65 x 10(7) cells), exhibiting a less-than-significant enhancement in yield. The CD34(+) cell contents recovered in the concentrates up to four cycles (r = 0.989) and up to seven cycles (r = 0.993) were strongly correlated with the original content of the CD34(+) cells. Engraftment was obtained in all patients except one patient infused with purified CD34(+) cells. This latter result confirmed the hematopoietic potential of the cell populations recovered. Granulocyte recovery (defined as an absolute neutrophil cell count > or = 500/microL for a period of three consecutive days) ranged from 8 to 25 days (median: 16 days) post-transplantation. No hemolytic reaction was observed in any of the patients. Our results confirmed the efficacy of BM processing cycles with the COBE Spectra device. However, we could not conclude that the large-volume apheresis for BM processing significantly enhanced the yields of HPC. The final recovery of CD34(+) cells after processing could be predicted from the CD34(+) cell content of the original collected marrow.