We evaluated the long-term outcome of very dose-intensive chemotherapy (TCC-NHL-91) for advanced intermediate-grade lymphoma, in which an eight-cycle regimen with 11 drugs was given with granulocyte colony-stimulating factor (G-CSF) support (total 18 weeks). Fifty-nine patients were treated during February 1, 1991 and March 31, 2001 (median age: 48 years). Forty-three patients (73%) were in a high-intermediate risk or high-risk group (HI/H) according to the age-adjusted International Prognostic Index (aa-IPI). Forty-six patients received 7 or 8 cycles of therapy. Ten of 15 patients over age 60 stopped before 7 cycles. Forty-three patients with an initial bulky mass or a residual mass received involved-field radiation. Overall, 56 patients (95%) achieved complete remission (CR). Grade 4 hematotoxicity was observed in all patients. With a median follow-up of 128 months, the 10-year overall survival (OS) and progression-free survival (PFS) rates were 76% and 61%, respectively. Neither aa-IPI risk factors nor the index itself was associated with response, OS, or PFS. One patient died of sepsis during the therapy and one died of secondary leukemia. This retrospective study suggests that the TCC-NHL-91 regimen achieves high CR, OS, and PFS in patients with advanced intermediate-grade lymphoma up to 60 years old and may be a valuable asset in the management of this disease. Further evaluation and prospective studies of the TCC-NHL-91 are warranted.
The frequency and clinical significance of paraproteinemia in patients receiving hematopoietic stem cell (HSC) transplants were assessed. Of 66 patients with hematologic malignancies, excluding multiple myeloma who received an allogeneic or autologous HSC transplant, paraproteins were detected in 12 patients using immunoelectrophoresis. None of the patients showed paraproteinemia before HSC transplantation. The class of paraproteins most commonly seen was IgG. In 9 of these 12 patients (75%), a paraprotein was detected continuously after HSC transplantation for an average duration of 464 days, while others demonstrated a transient appearance of the protein. Paraproteinemia after HSC transplantation was not related to the stem cell source, (allograft vs. autograft), age, gender, viral infection and graft-vs.-host disease (GVHD). None of the patients developed plasma cell dyscrasia after the appearance of the paraprotein, while 1 patient developed secondary acute lymphoblastic leukemia. These findings indicate that paraproteinemia after HSC transplantation may be caused by an aberrant immune reconstitution after both allogeneic and autologous HSC transplantation. A long-term follow-up of patients with paraproteinemia after HSC transplantation is needed to confirm this finding in a larger series of patients.
<div>Abstract<p>Abnormal activation of hypoxia-inducible factor-1 (HIF-1), one of the most important transcription factors for the adaptation of cells to hypoxia, is frequently observed in numerous types of solid tumors. Dysregulation of HIF-1 induces tumor angiogenesis and enhances the expression of anti-apoptotic proteins and glycolysis-associated enzymes in cancer cells, which in turn leads to the promotion of tumor growth. In the present study, we examined the pathophysiologic role of HIF-1 in multiple myeloma. Furthermore, we explored the possibility that HIF-1 may be a molecular target for myeloma therapy. We identified constitutive expression of the hypoxia-inducible factor-1 α (HIF-1α)-subunit in established myeloma cell lines and in primary myeloma cells. Treatment with insulin-like growth factor-1 (IGF-1) significantly increased HIF-1α expression through activation of the AKT and mitogen-activated protein kinase signaling pathways. Inhibition of HIF-1 function either by echinomycin, a specific HIF-1 inhibitor, or a siRNA against HIF-1α resulted in enhanced sensitivity to melphalan in myeloma cells. This inhibition of HIF-1 also reversed the protective effect of IGF-1 on melphalan-induced apoptosis. Inhibition of HIF-1 drastically reduced both basal and IGF-1–induced expression of survivin, one of the most important anti-apoptotic proteins in myeloma cells. We conclude that HIF-1 inhibition may be an attractive therapeutic strategy for multiple myeloma. [Mol Cancer Ther 2009;8(8):2329–38]</p></div>
We compared apheresis products collected by two cell separators (Spectra and CS3000) for peripheral blood stem cell harvest (PBSCH), the total number of 110 apheresis procedures were done in 46 patients, who underwent two or three procedures over consecutive days. Respective results for apheresis products collected by Spectra and CS3000 were as follows (mean±standard deviation): whole white cells (×109), 16.2 (±14.0) and 11.1 (±9.15); mononuclear cells (×109), 9.21 (±6.59) and 7.74 (±6.12); CD34-positive cells (×108), 3.20 (±6.49) and 2.06 (±3.78); and CFU-GM (×105), 381 (±687) and 252 (±398). Thus, the ratio of mononuclear cells harvested using CS3000 was higher than that by Spectra (76% vs 68%, p<0.05). Although the ratio of CD34-positive cells was equal between the two products, a greater number of stem cells (CD34-positive cells and CFU-GM) was harvested with Spectra than CS3000 (p<0.05).These results showed that the purity of mononuclear cells harvested by CS3000 is superior to that by Spectra. However, Spectra was able to collect peripheral stem cells more efficiently.
Abstract Acute myeloid leukemia (AML) patients older than 65 years have a poor prognosis. Recently, CAR (C-reactive-protein/albumin ratio) has been actively reported as a prognostic index reflecting the nutritional and inflammatory status of elderly patients with solid tumors, but the usefulness of this index as a prognostic indicator in transplant-ineligible elderly AML patients has not been investigated. We studied genetic alterations and CARs in 188 newly diagnosed AML patients aged 65 years or older who were treated in a multicenter setting and had treated without HSCT. Both NCCN 2017 risk group, reflecting the genetic component of the tumor, and CAR, reflecting the inflammatory and nutritional status of the patient, successfully stratified the overall survival (OS) of the patients (2-year OS; CAR low vs high, 42.3% vs 17.8%, P < 0.001). Furthermore, in multivariate analysis, NCCN 2017 poor group and high CAR were extracted as independent poor prognostic factors predicting 2-year OS in the current study. We found, for the first time, that CAR at diagnosis predicted the prognosis of elderly patients with newly diagnosed AML treated without HSCT.
We conducted a clinical study of MTX-HOPE (day 1, methotrexate 20 mg per os (po); day 2, hydrocortisone 100 mg intravenous (iv), vincristine 1 mg iv; day 3,4 sobuzoxane 400 mg po; etoposide 25 mg po, repeating every 2 or 3 weeks) in 14 relapsed or refractory patients with non-Hodgkin's lymphoma. Ten responders were obtained 5 CR and 5 PR), and heavily treated patients were included in the responders. The median duration of over all survival which was estimated with Kaplan-Meier curve was 11.1 months (range, 2-18+ months), and the median duration of response was 6.9 months (range, 0.8+ -16.4+ months). Out of the 14 patients,eleven were treated with this regimen in an outpatient setting. Grade 4 neutropenia and thrombocytopenia were observed in 4 and 2 patients,and grade 3 GPT-elevation and stomatitis in two and one, respectively. This newly developed MTX-HOPE therapy may be a promising treatment option for such patients as are intolerable for high-dose chemotherapies with PBSC rescue or wish for outpatient therapy.
