Myelodysplastic syndrome with myelofibrosis in which azacitidine therapy was effective and cord blood transplantation was carried out.

Myelodysplastic syndrome with myelofibrosis (MDS-F) is a disease with a poor prognosis, and patients with this condition are at an increased risk of engraftment failures after allogeneic hematopoietic stem cell transplantation (SCT). Azacitidine (AZA) is effective in high-risk MDS patients. However, the effects of AZA on MDS-F have not been elucidated. AZA was administered to a 62-year-old male with MDS-F for 7 days at a dose of 75 mg/m2. Hematological improvements were observed after only 1 course of treatment. No suitable donor was found through the Japan Marrow Donor Program; therefore, the patient underwent umbilical cord blood transplant (UCBT). Neutrophil engraftment was observed on day 21 after the transplant procedure. He developed acute graft versus host disease (GVHD) of the skin (stage 3/grade II), but it could be controlled using prednisolone. Chronic GVHD was not observed and he was discharged in good general condition on day 68. While treatment prior to allogeneic SCT of MDS-F has not been established, in the present case, the hematological improvement brought about by AZA likely contributed to the patient's positive response to UCBT.

Epstein-Barr Virus-associated Lymphoproliferative Disorder with Encephalitis Following Anti-thymocyte Globulin for Aplastic Anemia Resolved with Rituximab Therapy: A Case Report and Literature Review.

Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) sometimes occur following Anti-thymocyte globulin (ATG) administration for allogenic stem cell transplantation but are rare in aplastic anemia (AA) patients. A 55-year-old woman with AA following ATG developed refractory fever and was diagnosed with EBV-LPD. She was successfully treated with weekly rituximab monotherapy; however, she developed EBV encephalitis. She was admitted to the intensive care unit and finally recovered from unconsciousness. EBV-LPD should be considered after ATG for AA when symptoms appear. Because EBV-LPD following ATG for AA can rapidly progress, weekly monitoring of EBV-DNA and early intervention may be necessary.

Comparison of levofloxacin and garenoxacin for antibacterial prophylaxis during neutropenia.

Levofloxacin (LVFX) is widely used for antibacterial prophylaxis during neutropenia. Garenoxacin (GRNX), which has been investigated in Japan, has stronger antibacterial activity than LVFX against gram-positive bacteria; however, no studies have compared the effectiveness of LVFX and GRNX. We retrospectively analyzed 42 patients with acute leukemia and 32 patients who underwent hematopoietic cell transplantation. Thirty-one patients before September 2009 received GRNX, and subsequent 43 patients received LVFX. We compared the cumulative incidences of positive blood and stool cultures. There was no significant difference in the incidence of bacteremia between the GRNX and LVFX groups. However, while gram-negative bacteria were detected in 80% of the patients with bacteremia in the GRNX group, they were detected in only 33% of the patients with bacteremia in the LVFX group. Patients in the GRNX group more frequently experienced positive stool cultures than those in the LVFX group, and this was confirmed by a multivariate analysis. Gram-negative bacteria accounted for 100 and 67% of the stool culture results in the GRNX and LVFX groups, respectively. While both fluoroquinolones may be appropriate antibacterial prophylactic agents for neutropenia patients with hematological malignancies, vigilance for gram-negative bacterial infections should be exercised when GRNX is used as prophylaxis.

Clinical significance of granule-containing myeloma cells in patients with newly diagnosed multiple myeloma.

The clinical features and prognostic significance of myeloma cells containing granules remain unclear. The purpose of this retrospective study was to investigate the clinical significance of granule-containing myeloma cells in patients with newly diagnosed multiple myeloma (NDMM). We retrospectively analyzed the records of 122 patients diagnosed with NDMM between January 2007 and December 2013. Granule-containing myeloma cells were defined as myeloma cells that exhibited three or more granules in their cytoplasm by May-Giemsa staining. The patients were classified into two groups, the granule-containing myeloma (GM) and nongranule-containing myeloma (non-GM) groups, depending on the proportion of myeloma cells that contained granules (cut-off value: 10%). There were 25 (20.5%) patients in the GM group. Patients in the GM group displayed significantly higher CD56 and CD49e expression than those in the non-GM group (t-test, P = 0.027 and 0.042). None of the patient characteristics differed significantly between the two groups. There was no significant difference in the chemotherapy profiles of the two groups, and the overall response rates of the two groups were similar. During the median follow-up period of 33.9 months, the overall survival (OS) in the GM group was similar to that in the non-GM group; 4-year OS of the GM and non-GM groups were 78.5% and 51.9%, respectively (P = 0.126). We concluded that cases of NDMM involving granule-containing myeloma cells are not infrequent. Moreover, CD56 and CD49e expression was significantly higher in the presence of myeloma cell populations, and the presence of granules did not affect survival.

[Human herpesvirus 8-negative primary effusion lymphoma-like lymphoma with t(8;14)(q24;q32)].

Primary effusion lymphoma (PEL) is a large B-cell lymphoma proliferating only in the body cavity effusion. It often occurs in advanced AIDS patients and is associated with human herpesvirus 8 (HHV-8). On the other hand, HHV-8 negative effusion lymphoma, which is different from PEL in many ways, has also been reported and is referred to as HHV8-unrelated PEL-like lymphoma. This lymphoma is very rare and its clinical characteristics have not yet been fully clarified. We therefore report an HIV seronegative elderly patient with HHV8-unrelated PEL-like lymphoma. An 89-year-old woman was admitted to our hospital due to general fatigue and dyspnea. The patient presented with left pleural effusion in the absence of lymphadenopathy and tumor masses. The pathological examination of the pleural effusion showed proliferation of atypical large lymphoid cells, which were positive for CD19, CD20, CD10, CD38, CD7, BCL2 and BCL6 but negative for CD5, CD30, MUM1, surface immunoglobulin, HHV-8 and EBV. Cytogenetic analysis showed a complex karyotype including t(8;14)(q24;q32). The pleural effusion decreased in response to monotherapy with oral low-dose etoposide, but recurrence was detected 7 months later. Rituximab was transiently effective for the recurrent pleural effusion, but the patient died of lymphoma exacerbation 13 months after the diagnosis.

Pharmacokinetics for once-daily modified release formulation of tacrolimus hydrate in unrelated hematopoietic stem cell transplantation.

A once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed in response to the problem of nonadherence. However, there have been no data available about the efficacy of Tac QD conversion from intravenous Tac (Tac i.v.) in allogeneic hematopoietic stem cell transplantation (allo-SCT). We analyzed the pharmacokinetics (PK) of Tac QD in allo-SCT recipients. A total of 10 patients with hematological malignancies who received allo-SCT from unrelated donors were enrolled. Patients received Tac i.v. at 0.03 mg/kg a day before transplantation. Administration of Tac i.v. was converted to Tac QD at a 1:4 ratio when the patients had recovered from regimen-related gastrointestinal toxicity and could tolerate oral medication. After conversion, six out of 10 patients (60 %) showed a sustained decrease in Tac exposure and required dose adjustment. The conversion from Tac i.v. to Tac QD should be performed under close medical supervision. Area under the curve (AUC) and the trough of Tac QD showed a correlation, and the trough should be maintained above 7.5 ng/ml to provide an adequate AUC. Although four patients received bone marrow from an HLA DRB1 1 antigen-mismatched unrelated donor, no patients developed grade III-IV acute graft-versus-host disease (GVHD). The modification of Tac QD to maintain a whole-blood trough concentration above 7.5 ng/ml may be as effective as Tac BID.

Impact of high-/middle-molecular-weight adiponectin on the synthesis and regulation of extracellular matrix in dermal fibroblasts.

Adiponectin has been shown to play a critical role in immunity. Recently, we reported that the adiponectin levels after allogeneic stem cell transplantation were higher in recipients with chronic graft-versus-host disease (cGVHD). However, the effects of adiponectin on extracellular matrix (ECM) and regulatory factors in dermal fibroblasts remain unclear. We compared the messenger RNA (mRNA) levels of collagen type1 (COL1A), fibronectin 1 (FN1), matrix metalloproteinase (MMP)1, MMP3, tissue inhibitor of metalloproteinase (TIMP)1, TIMP3, transforming growth factor-ß (TGF-ß), and TGF-ß receptor 2 (TGF-ßR2) in human normal dermal fibroblasts cultured with and without adiponectin, and we assessed the degree of synthesis of ECMs by immunofluorescent microscopy. Furthermore, we also assessed these mRNA levels after blocking of TGF-ßR2. Adiponectin induced higher mRNA levels of FN1, MMP1, MMP3, TIMP1, TIMP3, and TGF-ßR2 in a dose-dependent manner, but did not significantly affect COL1A or TGF-ß. In addition, adiponectin was shown to upregulate FN1, MMPs, and TIMPs after blocking of TGF-ßR2. Immunofluorescent microscopy revealed that adiponectin promoted a greater synthesis of ECMs than in the control in vitro. The finding that adiponectin upregulated ECM-associated factors might mean that high levels of adiponectin could modulate dermal fibrosis was observed in recipients with cGVHD. Further basic investigation is warranted to elucidate whether the adiponectin-pathway could be a target for the treatment of sclerotic cGVHD.

D-index dose not predict the development of pulmonary infection in acute myeloid leukemia patients undergoing consolidation chemotherapy with high-dose cytarabine.

The D-index is calculated as the area over the neutrophil curve during neutropenia. We investigated the impact of the D-index on pulmonary infection in 33 acute myeloid leukemia patients undergoing consolidation chemotherapy with high-dose cytarabine. There was no difference in the D-index between chemotherapies with and without pulmonary infection. The cumulative D-index (c-D-index) until the development of infection exceeded 4000 in four of five patients with pulmonary infection. Although there was no difference in the total D-index throughout the overall consolidation chemotherapy, the total D-index from induction to consolidation and the D-index at induction chemotherapy were higher in patients with pulmonary infection during consolidation than in those without it (P = 0.014 and 0.019, respectively). Our results showed that the cumulative effect of neutropenia might determine the risk of pulmonary infection in consolidation chemotherapy. We are planning a clinical trial of c-D-index-guided preemptive antifungal therapy.

Prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation.

OBJECTIVES: To evaluate the prophylactic role of long-term ultra-low-dose acyclovir for varicella zoster virus (VZV) disease after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We evaluated 141 patients who were planned to receive acyclovir at 200mg/day until the end of immunosuppressive therapy and for at least 1 year after HSCT in our center between June 2007 and June 2012. RESULTS: The cumulative incidence of VZV disease after HSCT was 4.5% at 1 year and 18.3% at 2 years. Protocol violation was the only independent significant factor that increased the incidence of VZV disease (hazard ratio (HR) 7.50, 95% confidence interval (CI) 3.60-15.63). Excluding patients with protocol violation, the discontinuation of acyclovir was the only significant factor for the development of VZV disease (HR 5.90, 95% CI 1.56-22.37). Six patients experienced breakthrough VZV disease, but four of these six had not taken acyclovir for several weeks before breakthrough VZV disease. On the other hand, the cumulative incidence of VZV disease after the cessation of acyclovir was 28.4% at 1 year and 38.0% at 2 years. The proportion of disseminated VZV disease was only 7% and no patient died directly of VZV disease. CONCLUSIONS: This study shows that long-term ultra-low-dose acyclovir appears to be effective for preventing VZV disease, especially disseminated VZV disease, after allogeneic HSCT. We recommend continuing acyclovir until the end of immunosuppressive therapy and for at least 1 year after HSCT, but additional strategies such as the administration of varicella vaccine may be needed to eradicate VZV disease.

Protection of ovarian function by two distinct methods of ovarian shielding for young female patients who receive total body irradiation.

To prevent ovarian dysfunction due to total body irradiation, we started ovarian shielding at our center (Saitama Medical Center, Jichi Medical University (SMC-JMU)) with a long source axis distance, which is different from the original method used at the University of Tokyo Hospital (UTH). We retrospectively analyzed the outcome of eight patients with a median age of 20.5 years from SMC-JMU and compared the results with the published data for eight patients with a median age of 22 years from UTH. The recovery of ovarian function was observed in five and six patients, respectively. The cumulative incidence of ovarian recovery, while treating relapse and death without ovarian recovery as competing risks, was 68.8 % at 2 years after transplantation in the total population, and there was no statistically significant difference between the two institutions (p = 0.85). Age and the history of previous chemotherapy did not affect the incidence of ovarian recovery. Two patients from each center had a relapse of leukemia. Overall, among the 11 patients who have survived without relapse, only one has not achieved ovarian recovery. In conclusion, ovarian shielding with both methods strongly protected ovarian function. However, we should continue to monitor the relapse rate among patients who undergo this procedure.

The safety and efficacy of acute graft-versus-host disease prophylaxis with a higher target blood concentration of cyclosporine around 500 ng/mL.

Cyclosporine (CsA) is the most widely used immunosuppressive agent for the prevention of acute graft-versus-host disease (GVHD). In a previous report, the incidence of acute GVHD was decreased by increasing the target blood concentration of CsA during a continuous infusion from 300 to 500 ng/mL without excessive toxicities. To confirm these results, we retrospectively analyzed 69 patients who received a continuous infusion of CsA at a higher target CsA level between 450 and 550 ng/mL (CsA500 group) and compared the clinical outcome with 29 patients who received CsA with a lower target concentration between 250 and 350 ng/mL (CsA300 group). The target concentration was determined based on the status of background diseases. Multivariate analysis revealed that the incidence of grade III-IV acute GVHD was significantly lower in the CsA500 group, although the incidence of grade II-IV acute GVHD was not different. Toxicities were equivalently observed between the two groups. Concomitant administration of voriconazole or itraconazole and higher hematocrit were identified as independent significant factors for higher concentration/dose ratio of CsA. The average dose of CsA to maintain CsA level around 500 ng/mL was higher compared with the previous study (3.4 mg/kg vs. 2.7 mg/kg at three wk), probably due to the difference in measuring method of CsA concentration. We conclude that continuous infusion of CsA with a target level between 450 and 550 ng/mL is a feasible and effective GVHD prophylaxis, but caution should be paid for the difference in measuring method.

Evaluation of the validity of preemptive therapy against cytomegalovirus disease based on antigenemia assay with a cutoff of 20 positive cells per two slides.

BACKGROUND: Preemptive therapy with ganciclovir (GCV) based on the results of a cytomegalovirus (CMV) antigenemia assay is a standard strategy for preventing CMV disease after allogeneic hematopoietic cell transplantation (HCT). However, the appropriate threshold of antigenemia-positive cells for deciding when to start GCV remains unclear. PATIENTS: This retrospective study included 80 recipients who received HCT from an alternative donor between 2007 and 2011. In 2009, we switched the threshold from 3 (3A group, n=24) to 20 (20A group, n=56) antigenemia-positive cells per two slides for preemptive therapy after HCT from an alternative donor. RESULTS: Early CMV disease within 100 days after HCT was observed in one patient in the 20A group. Antiviral agents including GCV, val-GCV, and foscarnet were given in 17 (71%) and 36 (64%) patients in the 3A and 20A groups, respectively (p=0.23). In 13 (23%) patients in the 20A group, the initiation of preemptive therapy was avoided because of the change in the cutoff value for CMV antigenemia. However, the total dose of GCV was not different between the two groups. The use of steroid was significantly associated with CMV antigenemia of at least 20 positive cells among patients with low-level antigenemia at the first detection. CONCLUSION: The increased threshold up to 20 positive cells for starting preemptive therapy was not associated with a significant increase in CMV disease, but the total dose of GCV was not reduced and there was one early CMV disease in the 20A group. We should explore how to identify patients who are at high risk for increased antigenemia among patients with low-level antigenemia, but at least, preemptive therapy should not be withheld in patients who are already receiving systemic steroid.

Comparison of the efficacy of peripheral blood stem cell mobilization using G-CSF alone from healthy donors and patients with hematologic malignancies.

Peripheral blood stem cell (PBSC) collection using granulocyte colony-stimulating factor (G-CSF) alone is superior to the combination of chemotherapy and G-CSF in terms of low morbidity, short duration of mobilization and low cost. We retrospectively compared the results of PBSC collection using G-CSF alone in 11 patients with malignant lymphoma (ML), 23 patients with plasma cell neoplasms (PCN) and 48 healthy donors. The geometric mean number of CD34(+) cells/kg obtained on the first day of collection was 0.99 × 10(6)/kg in ML patients, 2.26 × 10(6)/kg in PCN patients, and 3.36 × 10(6)/kg in healthy donors. The probability of collecting at least 1 × 10(6)/kg CD34(+) cells/kg during a single course of apheresis was 90.9% in ML patients, 95.7% in PCN patients, and 100% in healthy donors. In a multiple regression analysis of the CD34(+) cell yields on the first day of apheresis, we identified disease, the baseline white blood cell count (WBC), platelet count, and lactate dehydrogenase as independent significant variables. Particularly, disease was strongly associated with the CD34(+) cell yield, probably due to the difference in the number of previous chemotherapy cycles. In conclusion, the minimal dose of CD34(+) cells for autologous transplantation was collected in almost all patients with hematological malignancies. However, patients who have received repeated cycles of chemotherapy, such as patients with ML, and those who have low WBC counts and/or platelet counts may be at higher risk for poor mobilization.

Allotype analysis to distinguish the origin of varicella-zoster virus immunoglobulin G after allogeneic stem cell transplantation.

Varicella-zoster virus (VZV) reactivation is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Although previous studies have revealed that cellular immunity is important for suppressing reactivation, the role of humoral immunity against VZV has been poorly evaluated. We analyzed inherited polymorphisms in the immunoglobulin G (IgG) heavy chain constant regions of 50 HSCT recipient-donor pairs to distinguish donor-derived and recipient-derived antibodies. Twelve pairs were informative regarding the origin of IgG, since either the donors (n = 3) or recipients (n = 9) were homozygous null for the IgG1m(f) allotype. In these 9 homozygous-null recipients, allotype-specific IgG against VZV were measured by enzyme-linked immunosorbent assay and compared with measles-IgG. All 9 homozygous-null recipients were monitored for more than 1 year after HSCT, with (n = 4, localized zoster) or without (n = 5) clinical VZV disease. In 3 patients with VZV disease, donor-derived IgG against VZV was elevated between 500 to 700 days after HSCT after the episode of VZV disease. In 1 patient who suffered from VZV disease just before HSCT, donor-derived VZV IgG was elevated within 3 months after HSCT. On the other hand, 2 patients who received reduced-intensity conditioning (RIC) transplantation from an IgG1m(f) null donor maintained recipient-derived IgG against VZV for more than 1 year, whereas it was decreased within 3 months in 1 recipient who received conventional conditioning. In conclusion, the production of anti-VZV IgG by recipient plasma cells persists long after RIC. In patients without symptomatic VZV reactivation, donor-derived anti-VZV IgG did not reach titers comparable to those measured in healthy virus carriers.

Long-term persistence of limited HTLV-I Tax-specific cytotoxic T cell clones in a patient with adult T cell leukemia/lymphoma after allogeneic stem cell transplantation.

PURPOSE: Adult T cell leukemia/lymphoma (ATL) is a highly aggressive malignancy of T cells caused by human T cell lymphotropic virus type 1 (HTLV-1). Recent clinical studies have suggested that allogeneic stem cell transplantation (HSCT) improves the clinical course of ATL by harnessing a graft-versus-ATL effect, and that donor-derived HTLV-1 Tax-specific CD8(+) cytotoxic T cells (CTLs) contribute to the graft-versus-ATL effect after HSCT. However, little is known about the immunological characteristics of Tax-specific CTLs in ATL patients who underwent HSCT. METHODS: We serially analyzed frequencies, differentiation, functions and clonal dynamics of Tax-specific CTLs in paired samples of peripheral blood (PB) and bone marrow (BM) from an ATL patient after HSCT at the single-cell level. We used flowcytometric and single-cell T cell receptor (TCR) repertoire analysis methods without culture steps. RESULTS: Donor-derived Tax-specific CTLs effectively suppressed HTLV-1 replication in both PB and BM at least during chronic graft-versus-host disease after HSCT. Furthermore, Tax-specific CTLs had comparable properties between BM and PB, except for preferential accumulation in BM rather than PB. Tax-specific CTLs persistently existed as less-differentiated CD45RA(-)CCR7(-) effector memory CTLs based on predominant phenotypes of CD27(+), CD28(+/-) and CD57(+/-). Our approach using single-cell TCR repertoire analysis method showed highly restricted oligoclonal responses of Tax-specific CTLs, and TCR BV7- or BV30- expressing two predominant CTL clones persistently existed and maintained strong cytotoxic activities against HTLV-1 in both PB and BM over three years after HSCT. CONCLUSIONS: These findings about Tax-specific CTLs provide insights into future directions for studies on immunotherapy against ATL.

Fulminant hepatic failure caused by adenovirus infection mimicking peliosis hepatitis on abdominal computed tomography images after allogeneic hematopoietic stem cell transplantation.

Disseminated adenovirus disease after allogeneic hematopoietic stem cell transplantation (HSCT) is lethal in most cases, especially when it develops as fulminant hepatic failure. We encountered a patient who developed fulminant hepatic failure caused by adenovirus infection. She did not show manifestations of graft-versus-host disease and the results of serum tests for viral infection were all negative. Abdominal computed tomography (CT) findings were consistent with peliosis hepatitis. She died of fulminant hepatic failure, however, and pathological examinations of the liver specimen obtained after her death revealed adenovirus infection. In this report, we review the clinical characteristics and imaging findings of fulminant hepatic failure caused by adenovirus infection.

Rapid progression and unusual premortal diagnosis of mucormycosis in patients with hematologic malignancies: analysis of eight patients.

Mucormycosis is a rare but emerging group of life-threatening opportunistic mycoses. We described experience of eight patients who developed mucormycosis. These patients had developed hematologic malignancies, and none achieved complete remission. Six of the eight patients presented with neutropenia, five received corticosteroid, and four had concomitant hyperglycemia. The most frequent physical finding was fever, and five patients complained of facial pain, headache, or chest pain. Four patients presented with concomitant bacterial infection, pulmonary aspergillosis, or intestinal candidiasis. Premortal diagnosis of mucormycosis was made in only one patient. Postmortem biopsy or autopsy was the diagnostic tool for the other patients. Although patients who were treated with amphotericin B survived longer than those treated with micafungin or voriconazole, all patients died due to the progression of mucormycosis. Estimated median survival was 23 days. Premortal diagnosis was rarely achieved as biopsy of infected tissues was the only diagnostic tool, and four patients who revealed dual infection were diagnosed with aspergillosis or bacterial infections. In patients with a high risk of mucormycosis presenting with pain and uncontrollable fever, mucormycosis should be included in the differential diagnosis. High dosages of liposomal amphotericin B should be given and surgical debridement should be performed promptly in cases highly suggestive of mucormycosis.

[High-dose methotrexate followed by whole-brain irradiation for primary central nervous system lymphoma patients--a retrospective study in a single institute].

This study analyzed retrospectively the clinical efficacy of combined therapy consisting of high-dose methotrexate (MTX), administered at a dose of 4 g/m2 every 2 weeks (maximum of 4 courses), followed by whole-brain irradiation for newly diagnosed primary central nervous system lymphoma (PCNSL) patients. Fifteen patients (median age: 59 years old; range: 26-79) were diagnosed by histological examinations or imaging techniques in our hospital. Of 15 patients, 12 (6: complete response; 6: partial response) achieved objective response, and the response rate was 80% (95% CI, 51.9-95.7%). The median follow-up time was 20 (range: 3-81) months, and the 3-year survival rate was 76%. The overall survival time was 71 months (95% CI, 23. 7-118.3 months), and the progression free survival was 15 months (95% CI, 0-43.8 months). The major toxicity (grade>or=3) of high-dose MTX included cytopenia (20%), acute respiratory distress syndrome (6.7%), and liver damage (6.7%). No patient evidenced complicated leukoencephalopathy in the follow-up time. The combined therapy of high-dose MTX followed by whole-brain irradiation showed a substantial antitumor efficacy in PCNSL patients. Prospective studies are required to determine the suitable treatment schedule for MTX and irradiation.

Gemtuzumab ozogamicin (GO) in relapsed/refractory patients with acute myeloid leukemia.

OBJECTIVE: Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 antibody, linked to calicheamicin, which has been approved in Japan recently. We conducted to evaluate the efficacy and toxicity of GO in our patients with relapsed or refractory AML retrospectively. PATIENTS AND METHODS: Data were collected between March 1, 2000, and March 1, 2006, on 10 patients with relapsed or refractory AML(excluding FAB: M3). Scheduled treatment was two doses of GO monotherapy, 14-28 days apart. RESULTS: Of the 10 assessable patients, two patients achieved CR. CR duration of one patient lasted for 52 months with post-remission treatment. Grade 4 neutropenia occurred in 9 patients, and the incidence of grade 3 or 4 thrombocytopenia was 100%, with no severe bleeding events. Two patients developed infusion-related adverse events that included grade 3 allergic reaction with shock status. Liver damage (grade 3 or 4) were observed in 40% of patients after GO treatment. No patient developed hepatic veno-occlusive disease including 2 patients who underwent HSCT. CONCLUSION: GO is a valuable new treatment option for relapsed or refractory AML patients, however, the benefit from single agent appears insufficient. On going clinical trials including combination with other antileukemic agents might better define the role of GO.