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ABSTRACT: Novel agents such as thalidomide, lenalidomide, and bortezomib have been shown to possess potent activity against multiple myeloma. However, the treatment strategy for patients who acquired resistance to these agents has not been established. In addition to switching drug classes, intensified treatment strategy, including increase in the dosage of current agents and addition of other agents, may be considered for these patients. We here describe 2 myeloma patients with acquired resistance to bortezomib or lenalidomide, in whom add-on therapy with low-dose cyclophosphamide was effective and tolerable. These cases suggest that add-on therapy with cyclophosphamide is one of the treatment options to overcome resistance to novel agents in patients with multiple myeloma. A larger prospective study is needed to clarify the efficacy and safety of this strategy for novel agent-resistant multiple myeloma.
Case reports in hematology. 01/2013; 2013:651902.
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Yoshihiro Kameoka,
Naoto Takahashi,
Kenichi Ishizawa,
Yuichi Kato,
Jugo Ito,
Osamu Sasaki, Kazunori Murai,
Hideyoshi Noji,
Makoto Hirokawa,
Katsusi Tajima,
Tsutomu Shichishima,
Yoji Ishida,
Hideo Harigae,
Kenichi Sawada
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ABSTRACT: High-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) is widely used as a salvage therapy in the treatment of refractory malignant lymphoma. To investigate the safety and feasibility of a high-dose MCNU, carboplatin, etoposide and cyclophosphamide (MCVC) regimen, we conducted a prospective multicenter trial. Thirty patients with relapsed/refractory/poor-risk non-Hodgkin lymphoma (NHL n = 27) or Hodgkin lymphoma (HD n = 3) were uniformly treated with an MCVC regimen and underwent auto-SCT. The median follow-up duration of the surviving patients was 67 months (56-133 months). The major toxicities were anorexia (94 %), diarrhea (80 %), nausea (79 %), febrile neutropenia (70 %), alopecia (67 %) and mucositis (60 %). Three patients developed severe left ventricular dysfunction, and two patients developed severe sinusoidal obstructive syndrome (SOS). Of these patients, two died without disease progression. Treatment-related mortality was 6.6 %. Late-onset adverse events including two cases of cytomegalovirus pneumonia and one of interstitial pneumonia were observed. In DLBCL (n = 13) and transformed FL (n = 2) patients, OS and EFS at 3 years were 72 and 46 %, respectively. These results suggest that the MCVC regimen followed by auto-SCT is a feasible and tolerable therapy for relapsed/refractory malignant lymphoma. However, cardiac toxicity due to high-dose cyclophosphamide and development of SOS can occur and should be carefully monitored. Further follow-up is needed to evaluate the long-term efficacy and safety of this regimen.
International journal of hematology 10/2012; · 1.17 Impact Factor
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Junichi Kameoka,
Naoto Takahashi,
Hideyoshi Noji, Kazunori Murai,
Katsushi Tajima,
Yoshihiro Kameoka,
Shinji Sato,
Tsutomu Shichishima,
Yoji Ishida,
Hideo Harigae,
Kenichi Sawada
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ABSTRACT: T-cell prolymphocytic leukemia (T-PLL) is characterized by a post-thymic immunophenotype, salient chromosome abnormalities, and an aggressive clinical course. However, cases in which these features are absent have been occasionally reported in Japan. Here, clinical and biological features of 13 T-PLL cases, diagnosed between 1992 and 2009 in the Tohoku region of Japan, were compared with three Western series. Median age was 64 (range 40-78) years old, and the male to female ratio (12:1) was higher than that of the Western series (P < 0.04). Presented manifestations were similar to those of Western cases, but central nervous system involvement, which is rare in Western cases, was observed in 3 of 13 cases (23 %) (P < 0.04). Immunophenotypic patterns were similar to those of Western cases, but HLA-DR was positive in 6 of 9 cases (67 %), which is distinct from Western cases (0-9 %) (P < 0.002). By chromosome analyses, 14q11 abnormality and trisomy 8q, which are common among Western cases (70-80 %), were not observed in any cases (P < 0.002). Morphologically, seven were classified as typical type, five as a small-cell variant, and one as a cerebriform variant. Seven cases experienced an aggressive course, whereas six experienced an indolent course over a median follow-up of 50 months. In contrast to Western cases, clinical courses were closely correlated with morphological types; 86 % of typical types were aggressive, whereas 83 % of small-cell types were indolent (P = 0.025). On the basis of these observations, together with previous Japanese cases in the literature, we propose that Japanese cases of T-PLL may constitute a variant.
International journal of hematology 04/2012; 95(6):660-7. · 1.17 Impact Factor
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Tomoaki Akagi,
Naoto Takahashi,
Kouhei Yamaguchi,
Kenichi Ishizawa, Kazunori Murai,
Katsushi Tajima,
Kazuhiko Ikeda,
Yoshihiro Kameoka,
Junnichi Kameoka,
Shigeki Ito,
Yuichi Kato,
Hideyoshi Noji,
Tsutomu Shichishima,
Jugoh Itoh,
Ryo Ichinohasama,
Hideo Harigae,
Yoji Ishida,
Kenichi Sawada
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ABSTRACT: To clarify the clinical outcome of peripheral T-cell lymphomas (PTCLs), we conducted a retrospective review comparing the outcomes of patients with PTCL (nodal peripheral T-cell lymphoma, unspecified, n=34 ; angioimmunoblastic T-cell lymphoma, n=12) to those with diffuse large B-cell lymphoma (DLBCL, n=48). All patients received CHOP-based chemotherapy without rituximab. PTCL patients presented at a more advanced clinical stage (91% vs. 65%, P<0.002) with a poorer performance status (26% vs. 17%, P<0.002) than DLBCL patients. The complete response rate among PTCL patients was significantly lower than among DLBCL patients (39% vs. 67%, P<0.008), as was the 3-year overall survival rate (26% vs. 50%, P=0.005), and Cox multivariate analysis revealed immunophenotype, performance status, and extranodal site involved to be significantly associated with shorter overall survival (P=0.045, P=0.007, and P=0.034, respectively). Our findings suggest that PTCL patients tend to have a poor prognosis associated with several initial risk factors. Moreover, the T-cell phenotype itself appears to have a significant impact on overall survival. Thus, standard CHOP chemotherapy may be inadequate for PTCLs, especially in patients with high-risk factors. The development of newly stratified therapies for the treatment of PTCLs would be highly desirable.
Journal of Clinical and Experimental Hematopathology 01/2011; 51(1):29-35.
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Tsutomu Shichishima,
Kazuhiko Ikeda,
Naoto Takahashi,
Junichi Kameoka,
Katsushi Tajima, Kazunori Murai,
Yoshiko Tamai,
Akiko Shichishima-Nakamura,
Kazuko Akutsu,
Hideyoshi Noji,
Masatoshi Okamoto,
Hideo Kimura,
Hideo Harigae,
Takashi Oyamada,
Toyomi Kamesaki,
Yasuchika Takeishi,
Kenichi Sawada
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ABSTRACT: To clarify whether measurement of serum haptoglobin (Hp) has impact on understanding pathophysiology in bone marrow failure (BMF) syndromes, we investigated concentrations of serum Hp by nephelometric procedure in 156 Japanese patients with BMF, including 54 aplastic anemia (AA), 50 paroxysmal nocturnal hemoglobinuria (PNH), and 52 myelodysplastic syndromes (MDS) patients. The frequencies with low concentrations of serum Hp (<42 mg/dL) in PNH patients (98.0%) were significantly higher than those in AA (27.8%; P < 0.0001) and MDS (38.5%; P < 0.0001) patients. In AA patients, white blood cell (WBC), absolute neutrophil, and platelet counts were significantly decreased in the group (n = 15) with low concentrations of serum Hp than in that (n = 39) with normal concentrations of it, and WBC counts were positively correlated with concentrations of serum Hp, suggesting that WBC counts may affect the concentrations. In MDS patients, hemoglobin concentrations and serum iron were significantly decreased and increased, respectively, in the group (n = 20) with low concentrations of serum Hp than in that (n = 32) with normal concentrations of it, and the values of serum iron were inversely correlated with concentrations of serum Hp, suggesting that ineffective erythropoiesis may affect the concentrations. Several AA and MDS patients with low concentrations of serum Hp had Coombs-negative autoimmune hemolytic anemia determined by immunoradiometric assay. In conclusion, several factors in conjunction with pathophysiology contribute to decrease of serum Hp in BMF.
International journal of hematology 04/2010; 91(4):602-10. · 1.17 Impact Factor
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ABSTRACT: Congenital blood coagulation factor XII (FXII) deficiency is a rare coagulation disease and an autosomal recessive trait. It is found by chance in many cases. We identified a novel mutation (Lys346Asn) in the FXII gene of a patient with FXII deficiency, designated as Factor XII Ofunato.
The proband was a 75-year-old Japanese woman with a prolonged activated partial thromboplastin time (52.8s). The FXII activity and antigen were greatly reduced (activity, 5%; antigen, 4.5%). We analyzed FXII gene of this patient using a direct sequencing method and characterized mutant FXII through in vitro expression studies.
Sequence analysis of the FXII gene revealed a G-->C point mutation at nucleotide 9845, resulting in Lys346 (AAG)-->Asn (AAC) replacement in the catalytic domain. Expression studies in Chinese hamster ovary cells demonstrated that mutant FXII (346N-FXII) showed a lower level of accumulation in the cells than wild-type. Secretion of 346N-FXII was greatly reduced in culture medium. We also investigated mRNA expression levels of wild-type and 346N-FXII in transfected cells using quantitative RT-PCR. Both mRNA expressions were equivalent levels. Pulse-chase experiments showed that 346N-FXII was extensively degraded intracellularly compared to wild-type. Using membrane-permeable inhibitors, we observed that degradation occurred in the pre-Golgi compartment and that proteasome apparently plays a central role in this process.
These results show that most 346N-FXII is degraded intracellularly through endoplasmic reticulum-associated degradation as the protein quality control system, resulting in an insufficient secretion phenotype.
Thrombosis Research 12/2009; 125(5):438-43. · 2.44 Impact Factor
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ABSTRACT: Adult T-cell leukemia (ATL) is an aggressive malignancy of peripheral T cells infected with human T-cell leukemia virus type 1 (HTLV-1). The prognosis of aggressive ATL patients remains poor because of its resistance to conventional chemotherapy. We examined the effect of deguelin, a naturally occurring rotenoid, on HTLV-1-transformed T-cell lines, KUT-1 and MT-2 cells. We found that deguelin suppressed cell proliferation and induced cell death in these cells. Immunoblot analysis showed the inhibition of survivin expression and signal transducers, and activators of transcription (STAT) 3 phosphorylation of both cells. We also observed the cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP) in deguelin-treated cells, indicating that deguelin induces caspase-dependent apoptosis in these cells. Furthermore, proteasome inhibitor MG132 prevented the down-regulation of survivin expression and STAT3 dephosphorylation by deguelin, suggesting that the action mechanism of deguelin involves the degradation of survivin and phosphorylated STAT3 through the ubiquitin/proteasome pathway. Our data indicate that deguelin presents a potent anti-proliferative effect in part via the down-regulation of survivin expression and STAT3 phosphorylation in HTLV-1-transformed cells. Deguelin merits further investigation as a potential chemotherapeutic agent for ATL.
Leukemia research 09/2009; 34(3):352-7. · 2.36 Impact Factor
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ABSTRACT: We analyzed cytosolic high-Km 5'-nucleotidase (cN-II) and deoxycytidine kinase (dCK) mRNA expression in bone marrow mononuclear cells (BMMNC) of patients with high-risk myelodysplastic syndrome (MDS) using quantitative real-time polymerase chain reaction (rt-PCR). At diagnosis, the cN-II mRNA expression of patients was higher than that of healthy volunteers, but the dCK mRNA expression showed no significant difference. Patients with ara-C-containing chemotherapies whose BMMNC showed a high level of cN-II expression (greater than the median value) had shorter median overall survival (15 months versus 22 months, p<0.01) and shorter median post-chemotherapy survival (10 months versus 16 months, p=0.012). These data suggest that the expression level of cN-II mRNA might be a prognostic factor of high-risk MDS.
Leukemia Research 10/2007; 31(10):1343-9. · 2.92 Impact Factor
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ABSTRACT: The percentage of hypochromic erythrocytes (%HYPO) and the reticulocyte hemoglobin content (CHr) have been used for the diagnosis of iron deficiency (ID). However, we found a discrepancy between %HYPO and CHr values in some hemodialysis patients. Hemodialysis patients receiving recombinant human erythropoietin (rHuEPO) with ID were defined as patients with a %HYPO value exceeding 5%. Five ID patients with a high CHr (group A) and 3 ID patients with a low CHr (group B) received 120 mg/week iron intravenously for 8 to 12 weeks. Changes in %HYPO, CHr, percentage of macrocytic erythrocytes (%MACRO), absolute reticulocyte count, immature reticulocyte fraction, and soluble transferrin receptor level were investigated over a 20-week period. CHrs were measured with 2 hematology analyzers: the Bayer HealthCare Technicon H*3 and the ADVIA 120. Patients in group A showed a significantly greater mean %MACRO (P < .01) and a lower mean red blood cell number (P < .05) than patients in group B. Even the mean CHr at baseline in group A was significantly higher than the mean CHr in the healthy subjects (P < .01), and hemoglobin levels increased in association with the reduction in rHuEPO dose following iron administration (P < .01). We found a group with high CHr, %HYPO, and %MACRO values among hemodialysis patients. Iron administration enables the rHuEPO dose to be reduced.
Laboratory Hematology 01/2005; 11(2):124-30.
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ABSTRACT: We describe a patient with persistent pure red cell aplasia due to human parvovirus B19 (HPVB19) infection during immunosuppressive therapy for refractory autoimmune hemolytic anemia (AIHA). The patient had been given corticosteroid (CS) and/or azathioprine for AIHA. During the course of treatment, reticulocyte count and hemoglobin levels decreased suddenly. Bone marrow aspirate showed erythroid lineage-specific aplasia with a few giant proerythroblasts, suggesting the presence of HPVB19 infection. The diagnosis of aplastic crisis due to HPVB19 infection was based on positive test results by polymerase chain reaction for HPVB19 immunoglobulin M (IgM) antibody and B19 DNA. Although splenectomy followed by administration of high-dose gamma globulin (HDIG) and plasma exchange were performed, the crisis and hemolysis recurred. Aplastic crises occurred several times when the B19 IgG result became negative and the CD4+ lymphocyte count was less than 300/microL. The patient showed complete recovery from anemia after CS was switched to cyclosporin A (CsA) and intermittent administration of HDIG. The result for B19 IgG antibody was continuously positive, and the DNA result became negative after these treatments. The results in this case indicated that concomitant administration of CsA and intermittent administration of HDIG can lead to cure of chronic anemia due to HPVB19 infection in patients with refractory AIHA.
International Journal of Hematology 10/2004; 80(3):250-3. · 1.27 Impact Factor
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Shigeki Ito,
Yoji Ishida,
Tatsuo Oyake,
Mamiko Satoh,
Yusei Aoki,
Shugo Kowata,
Toshiyuki Uchiyama,
Sanae Enomoto,
Takeshi Sugawara,
Hideharu Numaoka,
Keijiro Suzuki, Kazunori Murai
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ABSTRACT: The biological significance of CD56 antigen expression in patients with acute promyelocytic leukemia (APL) has been under investigation. We investigated the clinical and biologic features of CD56+APL. In our series, CD56 antigen was positive in 4 of 28 (14%) APL patients. No differences were found regarding age, gender, performance status (PS), initial leukocyte and platelet counts, lactate dehydrogenase (LDH) and fibrinogen (Fbg) levels according to CD56 expression. CD34 antigen was co-expressed in 3 of the 4 patients with CD56+ APL, in contrast to 2 of the 24 patients with CD56- APL (P = .01). Extramedullary relapse occurred in 3 of the 4 patients with CD56+ APL, in contrast to none of the 24 patients with CD56- APL (P = .001). Median remission duration was 4 months in CD56+ APL and was not reached in CD56- APL. The CD56+ population had a shorter remission duration (P < .0001) and disease-free survival (P < .0001). In contrast, no difference was found in overall survival. These results suggested that CD56 expression was associated with the leukemogenetic mutation at the primitive hematopoietic progenitor cell level and extramedullary relapse in APL patients treated with ATRA and chemotherapy.
Leukemia and Lymphoma 09/2004; 45(9):1783-9. · 2.58 Impact Factor
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Michihiro Uchiyama,
Chihaya Maesawa,
Akiko Yashima-Abo,
Mitsu Tarusawa,
Mamoru Satoh,
Takashi Satoh,
Yoji Ishida,
Shigeki Ito, Kazunori Murai,
Sanae Enomoto,
Taiju Utsugisawa,
Tomoyuki Masuda
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ABSTRACT: We used 3'-minor groove binder (MGB) technology to develop consensus fluorogenically labeled probes of the immunoglobulin heavy-chain (IgH) gene for detecting minimal residual disease (MRD) in B-cell non-Hodgkin lymphoma (B-NHL). Sequence data from 59 patients with B-NHLs revealed a narrow consensus region as a result of somatic hypermutations and variable VH usage, indicating that it would be difficult to design ordinary non-MGB probes. MGB probes, characterized by shorter length but higher melting temperature, are more suitable for this situation than ordinary non-MGB probes. In fact, the present data indicated that about 20% more cases were detectable with MGB probes (34/59, 57.6%) than with the non-MGB probes (23/59, 39.0%) designed by Donovan et al. MGB technology is useful for the design of consensus fluorogenically labeled probes of the IgH gene for detecting MRD.
Laboratory Investigation 08/2004; 84(7):932-6. · 3.64 Impact Factor
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ABSTRACT: We describe unusual cytogenetic findings in a 33-year-old male with blastic phase of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia. In addition to the t(9;22)(q34;q11), which was detected in all metaphases, a t(11;19)(q23;p13.3) was also identified as an evolutional change in all 20 metaphases. Fluorescence in situ hybridization (FISH) analysis showed that fusion signals of the ABL/BCR probes were found in 95% of blastic cells. Southern blotting and FISH analysis also revealed involvement of the MLL gene on 11q23. Clinical course was aggressive and the patient responded poorly to therapy. These findings suggest an association between Ph and 11q23 with poor prognosis, and that t(11;19)(q23;p13.3) was the essential pathogenic factor in our case.
Cancer Genetics and Cytogenetics 05/2004; 150(2):159-63. · 1.39 Impact Factor
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ABSTRACT: We reported three cases (42, 20 and 18-year-old men) of advanced nonseminomatous testicular germ cell cancer treated by salvage high-dose chemotherapy (HDC) supported by peripheral blood stem cell autotransplantation. Two cases which had been refractory to (B) EP (bleomycin, etoposide, cisplatin) and VIP (etoposide, ifosfmide, cisplatin) chemotherapies received one course of high-dose CEI (carboplatin 1,250 mg/m2, etoposide 1,500 mg/m2 and ifosfamide 7.5 g/m2), and the other case had been refractory to PVB (cisplatin, vinblastine, bleomycin) and VIP chemotherapies received one course of high-dose CEI and high-dose CCT (carboplatin 800 mg/m2, cyclophosphamide 6 g/m2 and thiotepa 720 mg/m2). Only one case achieved an incomplete remission by HDC, which was verified as a pathological complete response at the following salvage surgery, and has been alive with no evidence of disease for 68 months. The others achieved no change of disease following HDC and died from cancer progression. Hepatotoxicity, neurotoxicity and severe depression occurred, but not fatal in 2 cases.
Hinyokika kiyo. Acta urologica Japonica 03/2004; 50(2):77-80.
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Akiko Yashima,
Chihaya Maesawa,
Michihiro Uchiyama,
Mitsu Tarusawa,
Takashi Satoh,
Mamiko Satoh,
Sanae Enomoto,
Ken Sugawara,
Hideharu Numaoka, Kazunori Murai,
Taiju Utsugisawa,
Yoji Ishida,
Tomoyuki Masuda
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ABSTRACT: A real-time quantitative-polymerase chain reaction (RQ-PCR) targeting the immunoglobulin heavy chain (IgH) gene has been used for the quantification of minimal residual disease (MRD) in B-cell hematological malignancies. In non-Hodgkin lymphoma (NHL), experimental costs are increased, as a large number of primer-probe sets are required because of diversity, due to somatic and ongoing mutations of the IgH gene. We developed an allele-specific oligonucleotide (ASO) combined with a germline consensus probe-based RQ-PCR assay and examined MRD in peripheral blood stem cells (PBSC). The IgH consensus probes were adapted in seven (50%) of 14 amplifiable cases. Patients with heavily contaminating tumor cells in PBSC relapsed after PBSC transplantation. Our strategy will contribute to the development of a cost-efficient, precisely quantitative and systemic detection assay for MRD in NHL.
Leukemia Research 11/2003; 27(10):925-34. · 2.92 Impact Factor
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Michihiro Uchiyama,
Chihaya Maesawa,
Akiko Yashima,
Mitsu Tarusawa,
Takashi Satoh,
Yoji Ishida,
Shigeki Ito, Kazunori Murai,
Sanae Enomoto,
Taiju Utsugisawa,
Kazuo Motoyoshi,
Tomoyuki Masuda
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ABSTRACT: We have examined 72 patients with B-cell non-Hodgkin lymphoma (B-NHL) in order to search for consensus sequences of the immunoglobulin heavy chain (IgH) gene, and developed consensus fluorogenically labeled probes for use in an allele-specific oligonucleotide (ASO) real-time quantitative polymerase chain reaction (RQ-PCR) assay of minimal residual disease (MRD). We detected a clonal IgH variable region (VH) sequence in 51 (70.8%) of the 72 B-NHLs, the most frequent VH gene usages being VH3 and VH4 (45/51, 88.2%). It was possible to design three consensus fluorogenic probes for the VH3 gene and one for the VH4 gene avoiding these hypermutations. Our sequencing results suggested that consensus fluorogenic probes would be best based on the 5'-side of the framework region 3 (FR3) because the frequency of somatic hypermutations was significantly lower in the regions on which the probes were based than in the remaining parts of FR3 (P < 0.05). Nineteen (54.3%) of 35 B-NHLs with the VH3 gene and 5 (50%) of 10 with the VH4 gene had sequences identical to at least one of these probes. We found that probes containing one base substitution were still applicable for a MRD study, whereas those containing two or more were not. Therefore, our four probes were applicable for 37 (82.2%) of the 45 patients with VH3 or VH4. This limited number of probes makes a large-scale study of MRD in B-NHL more feasible.
Cancer Science 10/2003; 94(10):877-85. · 3.33 Impact Factor
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ABSTRACT: We describe an elderly patient with acute promyelocytic leukemia (APL), whose leukemic cells expressed CD56 antigen at relapse but not at diagnosis. Chromosome analysis revealed that blasts with t(8;15;17)(q24.1;q22;q11.2) increased from 4 of 20 cells (20%) at first relapse to 10 of 14 cells (71.4%) at second relapse. In addition, the positivity for CD56 expression on blasts judged by flow cytometric analysis using CD45 blast gating was also increased from 14.2% at first relapse to 75% at second relapse. Although conventional chemotherapy was performed for the initial disease and the first relapse, relapse developed again. Therefore, three courses of intensive postremission chemotherapy including concurrent administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) with cytarabine were performed after achievement of complete remission (CR) by the treatment with all-trans-retinoic acid (ATRA). Although PML-RARalpha mRNA was not detectable by reverse transcription polymerase chain reaction (RT-PCR), a third relapse occurred. This case demonstrated clonal evolution from a CD56(-) to a CD56(+) blast population and provided further support for the suggestion that CD56 expression might be an unfavorable prognostic factor in t(15;17) APL.
American Journal of Hematology 02/2002; 69(1):59-63. · 4.67 Impact Factor
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ABSTRACT: BACKGROUND
Even now, no definitely effective therapy is inducted to high risk myelodysplastic syndromes (MDS) and their leukemic stage (MDS-AML) except bone marrow transplantation.METHODS
Ten patients with high risk MDS and 6 with MDS-AML were treated with daily low doses of cytarabine (10 mg/m2/12h, infused over 2h) etoposide (50 mg/m2/day, infused over 2h).RESULTSFourteen of these patients were finally evaluated among whom 6 with high risk MDS and 3 with MDS-AML (64.3%) had complete remission, and 2 with high risk MDS (14.3%) achieved partial remission after this chemotherapy for 9 to 21 days. Three of 11 responders were resistant to the prior chemotherapies with single and low dose cytotoxic agents including cytarabine, etoposide, or aclarubicin. Although all of the patients who could be assessed developed severe marrow hypoplasia after chemotherapy, the nonhematologic side effects were mild enough to be tolerated.CONCLUSIONS
This combination chemotherapy must be effective and useful in high risk MDS and MDS-AML not only without prior chemotherapy but in cases which have been resistant to single and low dose oncostatic agent. Cancer 1996;78:422-6.
Cancer 12/1998; 78(3):422 - 426. · 4.77 Impact Factor
