Biomedical subjects

Tomomitsu Hotta

Publications and source records attributed to Tomomitsu Hotta.

At least 37 records · Page 2Linked to original sources

PubMed2005

Potential and origin of the hematopoietic population in human skeletal muscle.

While mononuclear cells isolated from murine skeletal muscle were shown to be capable of hematopoietic activity, similar hematopoietic cells (HC) recently were reported to exist in primate muscle. We investigated muscle-derived HC from young and adult human subjects. Although hematopoietic stem cells were rare in muscle, their frequency nonetheless was approximately four times greater than in peripheral blood. These cells in muscle appeared to originate from CD45(+) bone marrow cells. Our results suggested an additional function of human skeletal muscle as a reservoir of HC.

Adolescent↗

PubMed2005

Treatment of T-Cell lymphoma.

T-cell lymphoma composes 25% of lymphoid malignancies in Japan. Peripheral T-cell lymphoma (PTCL) unspecified and adult T-cell leukemia/lymphoma (ATLL) are major subtypes of T-cell lymphoma. The Japan Clinical Oncology Group (JCOG) has conducted 7 clinical trials for aggressive non-Hodgkin's lymphoma (NHL) including T-cell lymphoma. JCOG trials revealed that patients with ATLL had an extremely poor prognosis as compared with other peripheral T-cell lymphomas. A second generation combination chemotherapy including pentostatin (JCOG9109) could not improve the prognosis of patients with aggressive ATLL with the median survival time (MST) of 7.4 months. Subsequently, JCOG developed a new alternating multi-agent chemotherapy including MCNU and carboplatin with prophyractic use of G-CSF, resulting 35% of CR rate and 31% of 2-year OS. Considering the poor prognosis of aggressive ATLL patients, allogeneic stem cell transplantation seems to be another promising approach for a cure of the disease. New active agents such as chimeric monoclonal anti-CCR antibody are under developing for PTCL and ATLL.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Long-term results of a multicenter randomized, comparative trial of modified CHOP versus THP-COP versus THP-COPE regimens in elderly patients with non-Hodgkin's lymphoma.

In treating elderly non-Hodgkin's lymphoma (NHL) patients, it is particularly important to use drugs that have a low incidence of adverse events and high efficacy. In this multicenter study, THP (pirarubicin)-COP (cyclophosphamide, vincristine, and prednisolone) was compared to two thirds dosage of full CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen with regard to both adverse events and efficacy. For a third group, etoposide (E) was added to the THP-COP regimen (THP-COPE) in order to achieve high dose-intensity. Subjects were 486 previously untreated patients, aged 65 or older (range, 65-92 years; median, 74 years), with NHL. Subjects were randomly assigned to receive THP-COP, two thirds CHOP, or THP-COPE. Four hundred and forty-three patients were assessed for response and followed for 8 years after the last subject registered. The complete remission rates for the THP-COP, CHOP, and THP-COPE groups were 42.5%, 41.4%, and 48.0%, respectively. There was no difference in overall survival or progression-free survival among these 3 groups. In aggressive lymphoma, there was also no difference in complete response (CR) rate (45.3% in THP-COP, 44.9% in CHOP, 48.0% in THP-COPE), overall survival, and progression-free survival among these groups. The 5- and 8-year survival rates for all patients were 29.4% and 18.7%, respectively. The 5- and 8-year survival rates for patients with aggressive lymphoma were 27.4% and 17.4%, respectively. Although long-term survival for patients with aggressive lymphoma on our regimens was not worse compared to previous reports, the CR rate was lower. Because severe adverse events were not observed, higher dose chemotherapy may be directed to achieve better CR rates. In patients with T-cell-type lymphoma, the CR rate was greater after treatment with THP-COP (51.4%) or THP-COPE (57.7%) compared to treatment with CHOP (19.4%). Pirarubicin may be more useful for T-cell lymphoma than doxorubicin. Because adverse cardiac events were reported only in CHOP, adverse cardiac events might be low in the THP group.

Aged↗

PubMed2005

Assessment of the international prognostic scoring system for determining chemotherapeutic indications in myelodysplastic syndrome: Japanese retrospective multicenter study.

To standardize a rational therapeutic strategy of chemotherapy using the International Prognostic Scoring System (IPSS), we retrospectively analyzed 292 high-risk myelodysplastic syndrome (MDS) patients in 20 hospitals in Japan. Results of multivariate analysis of the data on patients who received all types of chemotherapy indicated that poor cytogenetics as shown by the IPSS was the only significant risk factor (P = .047). We then focused on the IPSS composition of each patient. The intermediate 2 (Int-2) category consisted of a heterogeneous group. We attempted to subdivide the category into Int-2A and Int-2B. Patients with good or intermediate cytogenetics had > or = 5% bone marrow (BM) blasts (Int-2A), and most of the other patients had poor cytogenetics and < or = 10% BM blasts (Int-2B). In the Int-2B category, overall survival for patients who received chemotherapy was significantly worse than for those who did not receive chemotherapy (P = .005). Most patients in the High category who had the diagnosis of MDS according to the World Health Organization classification had poor overall survival with or without chemotherapy. We propose the Int-2B and High categories may be considered possible high risk, whereas all patients in the Int-2A category and patients with more than 5% BM blasts in the Int-1 category may be categorized as being at possible intermediate risk. Our proposition may be useful for developing a chemotherapeutic strategy for patients with MDS in Japan.

Adult↗

PubMed2005

[The choice of second-line chemotherapy for malignant lymphoma].

The choice of second-line chemotherapy for malignant lymphoma in cases of both Hodgkin lymphoma and non-Hodgkin lymphoma depends on the results of first-line therapies. However, the trends in first-line therapy for malignant lymphoma have undergone significant changes over the last few years. The change has resulted from three facts: 1) the concept of dose intensity had to be revised, 2) newly-found prognostic factors have shown the need for therapy that takes risk grouping into consideration, and 3) new therapies, such as immunotherapy using monoclonal antibodies, have emerged. Based on these recent trends, this paper describes salvage therapies as a "recommendation" or "guideline" for cases of relapse or therapy-resistant disease which involve standard therapeutic measures.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Pulmonary non-caseating granuloma in Waldenström macroglobulinemia.

Lung involvement is rare in Waldenström macroglobulinemia (WM). We encountered a male patient with WM who complained of breathlessness. Chest X-ray revealed diffuse infiltrative shadow throughout the both lungs. Transbronchial biopsy showed infiltration of atypical plasmacytoid lymphocytes and non-caseating granuloma. We treated the patients with fludarabine phosphate, and both his symptom and X-ray findings were then improved. To our knowledge, this is the first case showing non-caseating granuloma with lung involvement of WM. We discuss a mechanism of non-caseating granuloma formation in this case.

Antimetabolites, Antineoplastic↗

PubMed2005

[Allogeneic bone marrow transplantation for chemotherapy-resistant T-prolymphocytic leukemia].

A 34-year-old female was referred to our hospital for the evaluation of atypical lymphocytosis. Leukocyte count at diagnosis was 17,900/microl with 58% atypical lymphocytes having a convoluted nucleus and prominent nucleoli. Because the leukocyte count increased to 43,600/microl, the patient was treated with 2'deoxycoformycin followed by CHOP combination chemotherapy. However, both treatments failed to achieve remission. We planned an allogeneic bone marrow transplantation from an HLA-matched unrelated donor. The patient was treated with Ara-C and etoposide before conditioning to decrease the high leukemia burden. After administration of total body irradiation (12 Gy in six fractions) and cyclophosphamide (total dose of 120 mg/kg) unmanipulated marrow cells were infused. Under prevention of GVHD by CsA and short-term MTX, leukocyte engraft was prompt at day 16, and acute GVHD grade II was observed. Because 9.4% of residual recipient type T-cells was seen with STR analysis on day 22, we decreased the dose of Cs'A. After the occurrence of mild acute GVHD, the residual T-cell number decreased. The patient is still in complete remission for up to 22 months after BMT. We conclude that allogeneic SCT is effective for the treatment of T-PLL.

Adult↗

PubMed2004

Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction.

Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. However, the responsible BM cells have not been fully identified. Here, we used 2 independent clonal studies to determine the origin of bone marrow (BM)-derived cardiomyocytes. First, we transplanted single CD34(-) c-kit(+)Sca-1(+) lineage(-) side population (CD34(-)KSL-SP) cells or whole BM cells from mice ubiquitously expressing enhanced green fluorescent protein (EGFP) into lethally irradiated mice, induced myocardial infarction (MI), and treated the animals with granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells to the damaged myocardium. At 8 weeks after MI, from 100 specimens we counted only 3 EGFP(+) actinin(+) cells in myocardium of CD34(-) KSL-SP cells in mice that received transplants, but more than 5000 EGFP(+) actinin(+) cells in whole BM cell in mice that received transplants, suggesting that most of EGFP(+) actinin(+) cells were derived from nonhematopoietic BM cells. Next, clonally purified nonhematopoietic mesenchymal stem cells (MSCs), cardiomyogenic (CMG) cells, that expressed EGFP in the cardiomyocyte-specific manner were transplanted directly into BM of lethally irradiated mice, MI was induced, and they were treated with G-CSF. EGFP(+) actinin(+) cells were observed in the ischemic myocardium, indicating that CMG cells had been mobilized and differentiated into cardiomyocytes. Together, these results suggest that the origin of the vast majority of BM-derived cardiomyocytes is MSCs.

Animals↗

PubMed2004

Upregulation of the viability of nucleus pulposus cells by bone marrow-derived stromal cells: significance of direct cell-to-cell contact in coculture system.

STUDY DESIGN: Upregulation of the viability of nucleus pulposus cells by coculture with bone marrow-derived stromal cells using a novel culture system. OBJECTIVES: The objective was to apply a novel coculture system having direct cell-to-cell contact between nucleus pulposus cells and bone marrow-derived stromal cells for stimulation of nucleus pulposus cells. SUMMARY OF BACKGROUND DATA: Reinsertion of nucleus pulposus cells was effective for treatment of intervertebral disc degeneration. However, obtaining highly viable nucleus pulposus cells was necessary to achieve successful results. Thus, an alternative method to upregulate the biologic and metabolic viabilities of nucleus pulposus cells was desired. METHODS: Nucleus pulposus cells and bone marrow-derived stromal cells were isolated from New Zealand white rabbits. A 6-well culture plate and insert with track-etched membrane having 0.4 microm pores at the bottom were used for coculture. Nucleus pulposus cells were monocultured, cocultured conventionally (having no direct cell-to-cell contact) with bone marrow-derived stromal cells, or cocultured having direct cell-to-cell contact with bone marrow-derived stromal cells. On day 4 of coculture, nucleus pulposus cells were evaluated for proliferation using WST-8 assay, deoxyribonucleic acid synthesis by measuring [H]-thymidine uptake, and proteoglycan synthesis by measuring [S]-sulfate uptake. We also quantified cytokines in supernatants from the culture system. RESULTS: Cell proliferation, deoxyribonucleic acid synthesis, and proteoglycan synthesis of nucleus pulposus cells were significantly upregulated in samples cocultured having direct cell-to-cell contact. Moreover, evaluations of supernatants revealed that growth factors associated with proliferation and cellular metabolism of nucleus pulposus cells were increased. CONCLUSIONS: Direct cell-to-cell contact in coculture system between nucleus pulposus cells and bone marrow-derived stromal cells accomplished significant upregulation in viability of nucleus pulposus cells.

Animals↗

PubMed2004

Immortalization of human nucleus pulposus cells by a recombinant SV40 adenovirus vector: establishment of a novel cell line for the study of human nucleus pulposus cells.

STUDY DESIGN: Establishment and characterization of a de novo cell line derived from human nucleus pulposus cells using a recombinant simian virus 40 (SV40) adenovirus vector. OBJECTIVES: To assess the feasibility of human nucleus pulposus cell line procurement and to evaluate the character of the resultant outcome to better understand the nature of human nucleus pulposus cells. SUMMARY OF BACKGROUND DATA: Despite recent advances in disc cell biologic research, the fundamental nature of nucleus pulposus cells, especially in the context of human cell lines, is still not well understood. Therefore, a broad-based analysis of these cells is of significant necessity. Because of the limited amount of existing human cells, establishment of an immortal cell line would greatly facilitate resource supply. METHODS: After release of informed consent, tissue samples of nucleus pulposus were obtained from the lumbar intervertebral disc of a 19-year-old man undergoing anterior fusion for burst fracture. Samples with no apparent damage were selected and digested enzymatically for primary culture and then were infected with recombinant SV40 adenovirus vector (Ad/SV40). The infected cells were maintained in culture for more than 40 population doublings, after which they were considered immortalized. Next, confirmation of expression of T antigen was performed and resultant immortalized cell lines were designated and classified as human nucleus pulposus cell line derived from Ad/SV40 infection-1 (HNPSV-1). HNPSV-1 cells were characterized and compared with their mother cells under two designated culture conditions: monolayer and three-dimensional. Morphologic and immunocytochemical analyses were performed at various intervals. Cell proliferation, DNA synthesis, proteoglycan synthesis, gene expression profiling, and karyotypic analyses were also performed. Moreover, HNPSV-1 cells were injected into rabbit discs to assess the presence of tumorigenesis. RESULTS: Recombinant SV40 adenovirus vector infected nucleus pulposus cells with relatively high efficiency (90%> at multiplicity of infection 100). HNPSV-1 demonstrated marked prolongation of cell life with continuous cell doublings for over 5 months (60-100 cell population doublings). Despite significant increase in cell proliferation and DNA synthesis when compared with its mother cells, resultant cell lines expressed strikingly similar cell morphology and functional characteristics. Atypical karyotypes were noted; however, no apparent tumorigenesis was seen in rabbit discs 24 weeks after injection of HNPSV-1. CONCLUSIONS: HNPSV-1 was successfully established using recombinant SV40 adenovirus vector. Results showed that human nucleus pulposus cells are capable of immortalization with maintenance of original cell characteristics. It is anticipated that these cells will be useful for in vitro studies of the biologic nature of human nucleus pulposus cells.

Adenoviruses, Human↗

PubMed2004

Platelets, after exposure to a high shear stress, induce IL-10-producing, mature dendritic cells in vitro.

There is evidence for immune system involvement in atherogenesis. In the present study the effect of platelets on dendritic cells (DC), an important immunologic regulator, was examined in vitro. Platelet-rich plasma, after exposure to shear stress, was added to human monocyte-derived immature DC, which were then examined for surface Ag expression, allogeneic T lymphocyte stimulatory activity, and cytokine production. After exposure, the number of anti-CD40 ligand (anti-CD40L) and anti-P-selectin IgG molecules bound per platelet was increased. These activated platelets induced DC maturation, as revealed by significant up-regulation of CD83, CD80, and CD86 Ags. The addition of platelets in the presence of IFN-gamma plus LPS significantly enhanced IL-10 production from immature DC. After platelet addition, mature DC provoked a significant proliferation of allogeneic naive T lymphocytes. These activated T cells showed lower IFN-gamma production than those stimulated by LPS- and IFN-gamma-treated DC. CD40L on the platelet surface was not involved in maturation of DC, as mAb to CD40L failed to block maturation. The effect of platelets was observed even if platelets and DC were separated using large pore-sized membranes or when platelets were depleted from plasma by centrifugation. Furthermore, it was abrogated after the depletion of protein fraction. Thus, soluble protein factors excreted from activated platelets contribute to IL-10-producing DC maturation.

Adult↗

PubMed2004

A competitive nucleic acid sequence-based amplification assay for the quantification of human MDR1 transcript in leukemia cells.

BACKGROUND: Because clinical drug resistance is caused by low-grade expression of a responsible gene, highly sensitive methods are desirable for its detection in clinical settings. We developed a quantitative nucleic acid sequence-based amplification (NASBA) assay for multidrug resistance-1 (MDR1) transcripts, and applied it to clinical samples. METHOD: MDR1 transcripts were amplified using the NASBA technique combined with sandwich hybridization of amplified MDR1 mRNA followed by chemiluminescence detection on an automated analyzer. Quantification of MDR1 mRNA was achieved through competitive coamplification of in vitro-generated RNA, which acts as an internal control. RESULTS: The competitive NASBA assay exhibited higher sensitivity (reliable detection limit was 100 copies of MDR1 mRNA) and linearity over a broader dynamic range (7 logarithmic orders) than the competitive reverse transcription-polymerase chain reaction assay. All 33 clinical samples obtained from patients with leukemia were successfully assayed, demonstrating its feasibility. MDR1 expression-compensated with beta-actin expression-ranged from 1.4 x 10(2) to 2.5 x 10(6) (median 4.8 x 10(5)) copies/microg RNA, while the range of MDR1 expression in peripheral blood samples from 15 healthy adults was from 8.9 x 10(4) to 5.2 x 10(5) (median 2.2 x 10(5)) copies/microg RNA. MDR1 expression in 8 of 33 clinical samples exceeded the median of healthy adult samples. CONCLUSIONS: The competitive NASBA assay is applicable to MDR1 mRNA quantification in clinical samples and would contribute to detection of clinical multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Induction of cytomegalovirus-specific CD4+ cytotoxic T lymphocytes from seropositive or negative healthy subjects or stem cell transplant recipients.

OBJECTIVE: We generated cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL) in vitro using dendritic cells (DC) pulsed with crude CMV antigens (Ag). PATIENTS AND METHODS: Mononuclear cells from healthy CMV-seropositive or seronegative volunteers and from stem cell transplant (SCT) recipients were cultured with CD14(+) monocyte-derived DC prepulsed with CMV Ag and then matured in vitro with lipopolysaccharide and tumor necrosis factor-alpha. After proliferation, cells were checked for phenotype (CD4/CD8), while killing activity was measured by 51Cr-release assay. RESULTS: CD4(+) T cells, the main proliferating cells from both seropositive and seronegative individuals, killed autologous Ag-pulsed DC but not vehicle-pulsed autologous DC or CMV-pulsed allogeneic DC. Similar CTL induction was accomplished from SCT recipients. Significant killing of autologous CMV-infected fibroblasts required 16-hour incubation as opposed to the standard 4-hour incubation, which was prevented by either a perforin inhibitor or anti-Fas ligand monoclonal antibody. CTL enhanced surface HLA-DR expression of CMV-infected fibroblasts, and their activity was neutralized by anti-HLA-DR monoclonal antibody. CONCLUSION: CMV-specific CD4(+) CTL were inducible with or without antiviral humoral immunity, even from immunosuppressed SCT recipients. These CTL showed perforin- and Fas/Fas ligand-mediated cytotoxicity after long-term (16-hour) contact with CMV-infected targets.

Antigens, Viral↗

PubMed2004

Competitive repopulation assay of two gene-marked cord blood units in NOD/SCID/gammac(null) mice.

In multiunit cord blood transplantation, hematopoietic stem cells from each unrelated cord blood (UCB) unit competitively reconstitute the hematopoietic system in a recipient. To evaluate the fate of the progeny of each UCB unit and to determine the effects of graft-versus-graft reaction, we established a novel competitive repopulation assay using NOD/SCID/gammac(null) mice in which human T lymphocytes develop from CD34+ cells. CD34+ cells from each UCB unit were labeled with recombinant lentivirus vectors carrying genes encoding either enhanced green fluorescent protein (EGFP) or enhanced yellow fluorescent protein (EYFP). Hematopoietic chimerism composed of both EGFP+ and EYFP+ cells was stably maintained up to 6 months after transplantation with purified CD34+ cells; the ratio of EGFP+ to EYFP+ cells in peripheral blood and bone marrow posttransplantation was equivalent to the ratio of these cells at transplantation. However, when mononuclear cells from two UCB units were cotransplanted with CD34+ cells, engraftment was highly competitive, with cells from only one or the other of the two UCB units surviving. Further subfractionations of mononuclear cells indicate that the skewed chimerism that is often observed in clinical multiunit cord blood transplantation may be mediated by the cooperation of both CD4+ and CD8+ T cells. The assay established here will be a useful tool for analyzing hematopoietic reconstitution in clinical multiunit cord blood transplantation.

Animals↗

PubMed2004

Clinical trials for malignant lymphoma in Japan.

The results of the clinical trials by the Lymphoma Study Group of the Japan Clinical Oncology Group (JCOG-LSG) and those of the industry-supported trials mainly conducted by the members of JCOG-LSG are summarized. In the treatment of advanced aggressive non-Hodgkin's lymphoma (NHL), we investigated the efficacy of granulocyte colony-stimulating factor (G-CSF)-supported, dose-intensified strategies. Based on the results of a randomized phase II study (JCOG9505), we conducted a phase III study, JCOG9809, comparing CHOP and biweekly CHOP. However, JCOG9809 was terminated early based on the results of a planned interim analysis, because it was deemed highly unlikely that biweekly CHOP would be superior to standard CHOP. For aggressive ATL, a G-CSF-supported, dose-intensified, multi-agent regimen (JCOG9303; LSG15) showed superior efficacy to our historical controls. To establish a new standard for ATL, we conducted a phase III study, JCOG9801, comparing LSG15 and biweekly CHOP. To develop new agents for lymphoid malignancies, we focused on irinotecan hydrochloride, interferon-alpha, cladribine and oral fludarabine. Among them, cladribine and oral fludarabine are promising for indolent B-cell malignancies. The Japanese phase I and II studies of rituximab, a chimeric anti-CD20 monoclonal antibody, in relapsed indolent and aggressive B-NHL showed high efficacy with minimal toxicities, which led us to conduct combination studies with chemotherapy for B-NHL. In addition, a phase I study of a radiolabeled anti-CD20 antibody (ibritumomab tiuxetan) was completed in 2003, and a phase II study for indolent B-NHL will be initiated. The multicenter trials by the JCOG-LSG and industry-supported new agent studies will contribute to further improvement in the treatment of malignant lymphoma.

Antibodies, Monoclonal↗

PubMed2004

Expression level of MDR1 message in peripheral blood leukocytes from healthy adults: a competitive nucleic acid sequence-based amplification assay for its determination.

Accurate quantification of multidrug resistance-1 gene (MDR1) expression in target cells would be of important therapeutic value in predicting cellular response to anticancer drugs. Because certain normal cells in peripheral blood physiologically express MDR1, increasing the sensitivity of the detection methods might result in confounding low-degree expression in tumor cells with physiologic expression in normal cells. The purpose of this study was to determine MDR1 mRNA expression levels in peripheral blood leukocytes obtained from healthy adult volunteers using a competitive nucleic acid sequence-based amplification (NASBA) assay. We determined the reference intervals of MDR1 mRNA expression in peripheral blood obtained from 98 healthy adults by measuring its expression with the quantitative NASBA assay between 5.50 x 10(4) copies/microg RNA and 6.76 x 10(5) copies/microg RNA. The new reference intervals were evaluated using a number of sensitive or resistant cell lines as control; positive or negative MDR1 expression was clearly demonstrated. We also reevaluated MDR1 expression levels in leukemia cells obtained from patient peripheral blood; 18 of 31 samples (58%) exceeded the newly established upper reference limit. The cutoff value established could be used to distinguish significant MDR1 expression in tumor cells from physiologic expression in certain normal cells coexistent in peripheral blood.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Phase III study of ranimustine, cyclophosphamide, vincristine, melphalan, and prednisolone (MCNU-COP/MP) versus modified COP/MP in multiple myeloma: a Japan clinical oncology group study, JCOG 9301.

To investigate whether combination chemotherapy with vincristine, cyclophosphamide, prednisolone, and melphalan (COP/ MP) with the addition of ranimustine (MCNU) (MCNU-COP/MP) is superior to the slightly modified COP/MP (mCOP/MP) regimen in multiple myeloma (MM), a multicenter randomized study was performed. Two hundred ten patients with newly diagnosed, overt MM not treated with chemotherapy were enrolled from 32 institutions of the Lymphoma Study Group of the Japan Clinical Oncology Group and were randomized to receive either MCNU-COP/MP or mCOP/MP. The response rate (RR) to mCOP/MP was 43.7% (95% confidence interval [CI], 33.9%-53.8%] and to MCNU-COP/MP was 56.1% (95% CI, 46.1%-65.7%) (P = .097). The progression-free survival (PFS) was significantly longer for patients treated with MCNU-COP/MP than for patients treated with mCOP/MP (median, 23.0 months [95% CI, 18.9-25.8] versus 15.8 months [95% CI, 14.1-19.4]) (P = .014). However, no significant difference in overall survival rate (OS) was observed between the groups (median, 49.9 months [95% CI, 40.4-59.1] versus 44.0 months [95%, CI, 32.8-59.8]) (P = .75). Grades 3 and 4 hematological toxicities were more frequently observed with MCNU-COP/MP than with mCOP/MP, but the incidence of grades 3 and 4 nonhematological toxicities was low in both groups. In conclusion, MCNU-COP/MP in comparison with mCOP/MP improved RR and PFS in overt MM; however, this outcome did not contribute to prolonging OS, indicating that addition of MCNU to mCOP/MP has no benefit on survival.

Adult↗

PubMed2004

Multicenter prospective study of interferon alpha versus allogeneic stem cell transplantation for patients with new diagnoses of chronic myelogenous leukemia.

We compared interferon alpha (IFN-alpha) therapy with stem cell transplantation (SCT) for patients with chronic-phase chronic myelogenous leukemia in a multicenter prospective study to investigate the optimal indication and timing of SCT, especially from HLA-matched unrelated donors. Of 257 eligible patients, 145 patients who were younger than 50 years were assigned to the IFN-alpha cohort (n = 87) or the SCT cohort (n = 58), according to family donor availability. In the IFN-alpha cohort, 52 patients received IFN-alpha and chemotherapy (the IFN1 group), and 35 patients received an SCT from an unrelated donor (the U-SCT group). In the SCT cohort, 47 patients received an SCT from a related donor (the R-SCT group). In the IFN1 group, 88% of the patients achieved a complete hematologic response, and 33% achieved a complete cytogenetic response. At a median follow-up period of 53 months, the predicted 6-year survival rate was 72% in the IFN1 group, 81% in the R-SCT group, and 81% in the U-SCT group. When overall survival was evaluated for the IFN-alpha and R-SCT cohorts by intention to treat according to family donor availability, the 6-year survival rates were 76% and 84%, respectively. When the outcomes of the U-SCT and IFN1 groups were compared, the survival rate of U-SCT group patients was significantly better than for IFN1 group patients without a major cytogenetic response and seemed better for IFN1 group patients younger than 35 years. Therefore, U-SCT may be recommendable to patients who fail to achieve a major cytogenetic response in IFN-alpha therapy and to younger patients.

Adult↗