Kazuo Muroi

Unrelated allogeneic bone marrow-derived mesenchymal stem cells for steroid-refractory acute graft-versus-host disease: a phase I/II study

We conducted a multicenter phase I/II study using mesenchymal stem cells (MSCs) manufactured from the bone marrow of healthy unrelated volunteers to treat steroid-refractory acute graft-versus-host disease (aGVHD). Fourteen patients with hematological malignancies who suffered from grade II (9 patients) or III aGVHD (5) were treated. Affected organs were gut (10 patients), skin (9 patients), and liver (3 patients). Seven patients had two involved organs. The median age was 52. No other second-line agents were given. MSCs were given at a dose of 2xa0×xa0106 cells/kg for each infusion twice a week for 4xa0weeks. If needed, patients were continuously given MSCs weekly for an additional 4xa0weeks. By week 4, 13 of 14 patients (92.9xa0%) had responded to MSC therapy with a complete response (CR; nxa0=xa08) or partial response (PR; nxa0=xa05). At 24xa0weeks, 11 patients (10 with CR and 1 with PR) were alive. At 96xa0weeks, 8 patients were alive in CR. A total of 6 patients died, attributable to the following: underlying disease relapse (2 patients), breast cancer relapse (1), veno-occlusive disease (1), ischemic cholangiopathy (1), and pneumonia (1). No clear adverse effects associated with MSC infusion were observed. Third party-derived bone marrow MSCs may be safe and effective for patients with steroid-refractory aGVHD.

Clinical features of de novo CD25-positive follicular lymphoma

Abstract CD25 expression in follicular lymphoma (FL) has not yet been investigated. Eighty-five patients with newly diagnosed FL were retrospectively evaluated. On two-color flow cytometric analysis, CD25 was detected on CD19 + and CD20 + lymphoma cells. CD25 expression in FL tended to be higher than in reactive lymphadenopathy, but was lower than in diffuse large B-cell lymphoma. Patients with CD25 + FL (n = 12) showed clinical features of elevated soluble interleukin-2 receptor (IL-2R) levels, B symptoms and an advanced age compared with CD25 − FL (n = 73). The overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) in patients with CD25 + FL were significantly inferior to those with CD25 − FL (ORR, 60 vs. 93%; 2-year PFS, 32 vs. 80.3%; 6-year OS, 47.4 vs. 85.9%, respectively). Multivariate analysis demonstrated that CD25 positivity is an independent prognostic factor for PFS and OS in FL. CD25 + FL may constitute a distinct subgroup associated with aggressiveness and an inferior prognosis.

Clinical features of de novo CD25+ diffuse large B-cell lymphoma

Abstract CD25 (interluekin-2 receptor) expression in diffuse large B-cell lymphoma (DLBCL) cells has been not examined. To characterize CD25+ DLBCL, 123 patients, who were newly diagnosed with DLBCL, were analyzed by single-color flow cytometry (FCM). CD25-positivity was significantly higher in DLBCL patients (n = 123; mean ± SD, 27.8 ± 30.6%) than in those with reactive lymphadenopathy (n = 16; mean ± SD, 8.6 ± 4.3%) and follicular lymphoma (n = 60; mean ± SD, 12.7 ± 12.4%). By two-color FCM, CD25/CD19 or CD25/CD20 dual positivity in DLBCL patients was shown: mean ± SD, 63.7 ± 25.5% (n = 13) and 55.0 ± 28.1% (n = 14), respectively. Eighty-two percent of the patients with DLBCL received rituximab combined with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. A cut-off value of 60% with CD25-positivity clearly divided patients with DLBCL into two groups: CD25-high or CD25-low DLBCL. Although clinical and immunophenotypic features were not significantly different in both groups, the former showed a significantly poorer response and more inferior progression-free survival than the latter. CD25 may be a new prognostic marker and could be a therapeutic target in DLBCL.

Use of cryoprotectant-depleted allogeneic peripheral blood stem cells for transplantation

Abstract Transplantation with cryopreserved allogeneic peripheral blood stem cells (PBSCs) from related donors is widely conducted in Japan. To freeze PBSCs, a solution containing dimethyl sulfoxide (DMSO), which can have various adverse effects, is added. DMSO-depleted allogeneic PBSCs were transplanted into 21 patients. The cryoprotectant was manually removed from thawed PBSCs and the cells were mixed with a solution containing citrate dextrose as an anticoagulant and RPMI-1640 medium. DMSO-depleted PBSCs were immediately infused into patients subjected to conditioning. Infusion-related adverse effects were only observed in three patients. The median neutrophil recovery (⩾0·5×109/l) and platelet recovery (⩾20×109/l) were 13·0 and 14·0 days, respectively. Only one patient with mixed-lineage leukemia in non-complete remission did not show engraftment, likely due to a second transplantation and a two-antigen disparity in human leukocyte antigen system A. The results suggest the removal of DMSO from thawed PBSCs to be safe and useful for transplantation.

Analysis of hemolysis in collected bone marrow for bone marrow transplantation

1473-0502/

Clinical outcome of non-surgical treatment for primary small intestinal lymphoma diagnosed with double-balloon endoscopy

see front matter 2013 Elsevier Ltd. All rights r http://dx.doi.org/10.1016/j.transci.2013.02.045 To the editor, Recently, the Japanese Marrow Donor Program (JMDP) reported that 3 patients with transplanted hemolyzed bone marrow (BM) showed severe adverse effects related to hemolysis [1]. In these cases, each BM was collected in a hospital and then shipped to another hospital where a patient had received conditioning. BM harvest and shipping were conducted according to the JMDP manual. Collected BM was infused directly into each patient because of ABO blood type compatibility. A hemolytic reaction was suspected just after the beginning of BM infusion based on symptoms such as nausea, vomiting, and blood pressure fluctuation and signs such as hematuria and an increase in serum lactic acid dehydrogenase (LDH) levels and total bilirubin values. Finally, hemolysis in the bags

CD56 Expression in Normal Immature Granulocytes after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract Primary small intestinal lymphoma (PSIL) is often treated with surgical resection, and therefore response to non-surgical treatment is rarely known. We retrospectively analyzed the clinicopathological features of 19 patients with PSIL, who had been diagnosed by double-balloon endoscopy (DBE) and had not received surgical treatment. The immunohistological phenotypes of 18 patients were B-cell lymphomas. Five patients had tumors within the jejunum, nine within the ileum and five in multiple sites including the duodenum. Most cases were in the low or low-intermediate risk group of the International Prognostic Index score. Seventeen patients received chemotherapy, with an overall response rate of 82.4%. The estimated overall survival at 5 years was 72.2%. Response to initial chemotherapy and levels of hemoglobin (Hb) and albumin (Alb) were identified as favorable prognostic indicators. We conclude that PSIL can be effectively diagnosed by DBE and shows a good prognosis with chemotherapy alone.