Promyelocytic crisis (PMC) of chronic myelogenous leukemia (CML) is relatively rare. We report a patient who progressed to PMC with a T315I mutation during the initial treatment with dasatinib for CML. He obtained hematological remission after combination therapy with all-trans retinoic acid and chemotherapy for PMC, and PML-RARA was not detected by FISH analysis. Arsenic trioxide (ATO) and imatinib therapy induced a second complete cytogenetic response, and PML-RARA mRNA detected by real-time quantitative RT-PCR dropped below the detection limit. Finally, allogeneic stem cell transplantation was performed. This case suggests that combination therapy with imatinib and ATO achieves favorable outcomes for PMC.

DOI： 10.11406/rinketsu.55.692

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The Sokal and Hasford scores were developed in the chemotherapy and interferon era and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, a new European Treatment and Outcome Study (EUTOS) scoring system was developed. We performed a multicenter retrospective study to validate the effectiveness of each of the three scoring systems. The study cohort included 145 patients diagnosed with CML in chronic phase who were treated with imatinib. In the EUTOS low- and high-risk groups, the cumulative incidence of complete cytogenetic response (CCyR) at 18 months was 86.9% and 87.5% (P = 0.797) and the 5-year overall survival rate was 92.6% and 93.3% (P = 0.871), respectively. The cumulative incidence of CCyR at 12 months, 5-year event-free survival and 5-year progression-free survival were not predicted using the EUTOS scoring system. However, there were significant differences in both the Sokal score and Hasford score risk groups. In our retrospective validation study, the EUTOS score did not predict the prognosis of patients with CML in chronic phase treated with imatinib. © 2013 The Authors.

DOI： 10.1111/cas.12321

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Language：English   Publisher：SPRINGER JAPAN KK  

POEMS syndrome is a monoclonal plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are an effective therapy, but optimal treatment options are still under debate. Bortezomib is an important agent for the treatment of patients with multiple myeloma and has recently been reported as efficacious in the treatment of patients with POEMS syndrome. We present a case of POEMS syndrome in a 33-year-old woman, who was successfully treated with BorDex (bortezomib and dexamethasone) combined with radiotherapy, and followed by ASCT. She was diagnosed with POEMS syndrome with a localized plasmacytoma of bone 5 months after her initial symptoms of heart failure. Her Eastern Cooperative Oncology Group (ECOG) performance status was 4. She was first administered BorDex therapy, which was subsequently combined with radiotherapy. Her general condition including heart failure dramatically improved after four cycles of BorDex therapy and radiation, resulting in partial response. After chemoradiotherapy, HDT and ASCT were performed. After treatment, she was able to walk unassisted and her plasma endothelial growth factor (VEGF) level decreased. She did not experience neurotoxicity induced by bortezomib. Bortezomib was well tolerated and we suggest that BorDex

DOI： 10.1007/s12185-013-1456-z

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A 23-year-old woman developed acute severe hepatitis and jaundice on day 183 after bone marrow transplantation from HLA-B antigen mismatched-related donor. The administration of prednisolone and cessation of the prescribed drugs resolved the liver injury. Drug lymphocyte stimulation test was positive for acyclovir, and liver biopsy indicated the characteristics of drug-induced liver injury (DILI) rather than graft-versus-host disease. Physicians should keep DILI in mind when considering differential diagnosis for liver complications after allogeneic cell transplantation.

DOI： 10.1007/s12185-013-1434-5

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Sinusoidal obstruction syndrome (SOS) is one of the severe complications of hematopoietic stem cell transplantation (HSCT). Systemic management including respiratory and circulatory support is necessary. In addition, abdominal paracentesis is often needed for pain relief and to reduce the pressure of tense ascites. Concentrated ascites reinfusion therapy (CART) involves the filtration, concentration, and reinfusion of drained ascites, which contributes to reuse of autologous proteins. CART has been reported as supportive therapy for patients with liver cirrhosis and cancer. We retrospectively reviewed the efficacy and safety of CART in three patients (two with acute myelogenous leukemia and one with chronic myeloid leukemia) who developed SOS after allo-HSCT. They all had symptomatic, tense, and diuretic-refractory ascites with right costal pain and marked weight gain. Two patients showed immediate improvement after CART. However, one patient experienced four CARTs with slow recovery. All patients are now alive and are being monitored as outpatients over 2 years with remission. No severe adverse event was observed related to CART, and 25.2-98.0 (median 30.2) grams of albumin was collected and reinfused. CART after paracentesis reduces protein loss in ascites by reinfusion of autologous protein instead of exogenous albumin preparations. Although transient fever is reported as a frequent adverse event, no events like severe bleeding or infection were observed. While its safety has not been fully established in patients with hematological disease after HSCT, CART may be a considerable supportive therapy for SOS with tense ascites. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation.

DOI： 10.1111/aor.12080

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Long-term observation has identified a pattern of continuing relapse in limited stage diffuse large B-cell lymphoma (DLBCL) treated by three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus involved-field irradiation. We retrospectively analysed 190 untreated patients with limited stage DLBCL treated by R-CHOP alone. All the patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Cases with a dose reduction of more than 20% were excluded from the study. Additional local irradiation was allowed in patients with partial response (PR). Five patients received additional local irradiation after PR at the end of the R-CHOP therapy. The median observation period was 52 months. Median age at diagnosis was 63 years. The responses to therapy were 180 complete responses, eight PR, and two progression of disease (PD). The 5-year progression-free survival and 5-year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD. The progression sites were the primary sites in 15 patients, outside the primary sites in 10, and undetermined in four patients. These results suggest that the 'standard' strategy of three cycles of R-CHOP followed by involved-field radiotherapy for limited stage DLBCL could be effectively replaced by six cycles of R-CHOP alone. © 2013 Blackwell Publishing Ltd.

DOI： 10.1111/bjh.12281

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

DOI： 10.3109/10428194.2012.720374

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We conducted a retrospective study to evaluate outcomes and prognostic factors of newly diagnosed patients with t(8;21) acute myeloid leukemia (AML). There were 70 patients (43 men and 27 women) with a median age of 48 years old (range, 17∼76 years old). Sixty-five patients achieved complete remission (CR) after induction chemotherapy. Fifty-seven patients received consolidation chemotherapy based on the policy of not performing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the time of first CR. Twenty-seven of the 57 patients relapsed (relapse rate, 47%). The median time from the achievement of the first CR to relapse was 307 days (96∼1,256 days). A white blood cell count of more than 25,400/μl at diagnosis was associated with a higher relapse rate than a white blood cell count of less than or equal to 25,400/μl (75% vs. 43%, P=0.04). Nineteen of the 25 relapsed patients who received re-induction therapy experienced a second CR (second CR rate, 76%). Twenty-six patients (5 with first CR, 12 with second CR, and 9 without remission) received allo-HSCT. The five-year overall survival and disease-free survival rates were 61% and 45%, respectively. Patients with t(8;21) AML had a high CR rate, but about half of them relapsed. However, this report could not show prognostic factors for the identification of patients who should receive allo-HSCT at the time of their first CR.

DOI： 10.11406/rinketsu.53.698

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Language：English   Publisher：INFORMA HEALTHCARE  

A multicenter retrospective analysis of the influence of pretransplant serum ferritin (SF) was performed in 261 adult recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), including 159 patients with acute myeloid leukemia (AML), 66 with acute lymphoid leukemia (ALL) and 36 with myelodysplastic syndrome (MDS). Patients were divided into subgroups according to the pretransplant SF level [< 1000 ng/mL (low) vs. 3 1000 ng/mL (high)] and disease status at transplant. A high SF level was significantly associated with high disease risk (p = 0.041), but pretransplant SF and disease risk were independent significant prognostic factors for overall survival (OS), disease-free survival (DFS) and non-relapse mortality rate (NRM) on multivariate analysis. The high-SF group showed a worse outcome than the low-SF group among both standard-risk patients (OS: 54% vs. 64%, p = 0.043; DFS: 46% vs. 57%, p = 0.031) and high-risk patients (OS: 16% vs. 35%, p = 0.001; DFS: 15% vs. 34%, p = 0.001). In conclusion, a high SF at transplant adversely influences the outcome of allo-HSCT regardless of disease risk in patients with acute leukemia and MDS.

DOI： 10.3109/10428194.2011.619607

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Imatinib is a drug for patients with chronic myeloid leukemia in its chronic phase. Poor drug adherence decreases response to therapy, because the therapeutic effect is related to the imatinib dose. Although the association between adherence and response to therapy has been assessed by various methods, the precise evaluation of adherence is difficult. We investigated the relationship between adherence and response to imatinib by an anonymous survey. Questionnaires were sent to 58 outpatients who had been treated with imatinib for more than one year. The return rate of the questionnaires was 82%. A lack of complete adherence was observed in 26% of all patients, but this lack of adherence was less than 90% in only 4 patients. When adherence was good, there was no relationship between adherence and response to imatinib in most patients, such as that reported in previous papers. We suggest that a better understanding of imatinib therapy by patients may contribute to the improvement of adherence.

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Language：English   Publisher：ELSEVIER SCIENCE INC  

To evaluate whether rescue with cord blood transplantation (CBT) could improve the poor survival after graft failure (GF), we surveyed the data of 80 adult patients (median age, 51 years) who received CBT within 3 months of GF (primary 64, secondary 16), with fludarabine-based reduced-intensity regimens with or without melphalan, busulfan, cyclophosphamide, and/or 2-4 Gy total-body irradiation (TBI). A median number of 2.4 x 10(7)/kg total nucleated cells (TNC) were infused, and among the 61 evaluable patients who survived for more than 28 days, 45 (74%) engrafted. The median follow-up of surviving patients was 325 days, and the 1-year overall survival rate was 33% despite poor performance status (2-4, 60%), carryover organ toxicities (grade 3/4, 14%), and infections (82%) prior to CBT. Day 100 transplantation-related mortality was 45%, with 60% related to infectious complications. Multivariate analysis showed that the infusion of TNC >= 2.5 x 10(7)/kg and an alkylating agent-containing regimen were associated with a higher probability of engraftment, and that high risk-status at the preceding transplantation and grade 3/4 organ toxicities before CBT were associated with an increased risk of mortality. In conclusion, in an older population of patients, our data support the feasibility of CBT with a reduced-intensity conditioning regimen for GE Biol Blood Marrow Transplant 17: 341-851 (2011) (C) 2011 American Society for Blood and Marrow Transplantation

DOI： 10.1016/j.bbmt.2010.09.005

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We retrospectively studied the association between iron overload and bloodstream infections (BSI) in the 100-day period following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia or myelodysplastic syndromes. Serum ferritin was measured before transplantation to evaluate iron overload. Of 114 adult patients who underwent transplantation between 2000 and 2008, 36 (32%) developed BSI. Of the 44 isolates, 63% were Gram-positive bacteria, 32% were Gram-negative bacteria, and 4% were fungi. The median time to the onset of the first BSI was day 28 (range day 0-95) after transplantation. Univariate analysis revealed a significantly higher incidence of BSI in the high (a parts per thousand yen1,000 ng/ml, n = 57) than in the low (< 1,000 ng/ml, n = 57) ferritin group (42.1 versus 21.1%, respectively, P = 0.017). Peripheral blood stem cell transplantation (PBSCT) (n = 23) showed a greater protective effect against BSI compared with bone marrow (n = 71) and cord blood (n = 20) transplantation. Pretransplantation serum ferritin (HR = 2.844, 95% CI: 1.180-6.859, P = 0.020) and PBSCT (HR = 0.135, 95% CI: 0.025-0.717, P = 0.019) were significant factors on multivariate analysis. In conclusion, pretransplantation serum ferritin significantly predicts BSI within the 100-day period after allo-HSCT.

DOI： 10.1007/s12185-011-0784-0

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A 50-year-old male was admitted to our hospital with pancytopenia. Peripheral blood examination showed pancytopenia (WBC 450/μl, Hb 7.3 g/dl, Plt 3,000/μl) and elevated FDP. Bone marrow examination demonstrated 38% blasts, 20% promyelocytes and Faggot cells. Cytogenetic analysis demonstrated the following: 46, XY, t(15;17)(q22;q12)[9]/46, XY, del(6)(q?), t(9;22)(q34;q11.2)[1]/46, XY[10]. PML/RARA and minor BCR/ABL were also detected by quantitative reverse transcription polymerase chain reaction of bone marrow cells (52,000 copies/μgRNA and 650 copies/μgRNA, respectively). The patient was diagnosed with acute promyelocytic leukemia. He was treated with all-trans retinoic acid monotherapy and achieved complete hematological remission 51 days after the initial treatment. Post-induction bone marrow examination demonstrated 46, XY[20] and PML/RARA 240 copies/μgRNA, whereas minor BCR/ABL was not detected. The patient's initial cytogenetic analysis suggested the presence of two distinct clones with t(15;17) and t(9;22), which to our knowledge have not previously been reported.

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We retrospectively surveyed patients who received a second transplantation for graft failure (GF) after allogeneic hematopoietic stem cell transplantation (SCT) in hospitals participating in the Kanto Study Group for Cell Therapy. A second SCT was performed in 21 of 45 patients with primary GF and in 13 of 15 with secondary GF. The median time between the first and second SCT was 49 days (range, 18-1204 days). The diagnosis included 28 patients with hematologic malignancies and 6 with aplastic anemia. Non-myeloablative or reduced-intensity conditioning was performed in 30 patients. Cord blood was frequently used as the source of stem cells followed by related donor peripheral blood, and unrelated bone marrow. Engraftment was achieved in 23 patients (68%). Conditioning regimen including total body or total lymphoid irradiation, was significantly associated with a higher engraftment rate. Overall survival at 5 years in all patients who underwent second SCT was 34%. Prognostic factors for better survival after second SCT were a time to second SCT longer than 90 days, the performance status at second SCT with 0 or 1, and the administration of tacrolimus for GVHD prophylaxis. The major cause of death after second SCT was infection. Although the outcome of a second SCT for graft failure remains poor, these findings suggest that the selection of patients as well as transplant methods, such as conditioning and GVHD prophylaxis, may contribute to survival.

DOI： 10.11406/rinketsu.51.390

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Language：English   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

We retrospectively investigated 31 myelodysplastic syndrome (MDS) patients receiving myeloablative hematopoietic stem cell transplantation (HCT) and focused on prognostic factors affecting the long-term outcome. Patients were classified according to the French-American-British classification and the HCT-comorbidity index was determined. Cytosine arabinoside or thiotepa combined with cyclophosphamide and total body irradiation was used as myeloablative conditioning in eight and 23 patients respectively. After a follow-up period of 0.8-14.2 years from transplantation (median: 6.4 years), 23 patients were alive in complete remission, and the 5-year overall survival (OS) and disease-free survival (DFS) rates were 79% and 72% respectively. The cumulative nonrelapse mortality (NRM) rate was 22% at 5 years. According to multivariate analysis, >= 20% blasts in the bone marrow and an HCT-comorbidity score >= 3 were significantly associated with poor OS and DFS. Patients with a high HCT-comorbidity score and male patients receiving transplantation from female donors were significantly more likely to have a higher NRM according to the univariate, but not the multivariate analysis. These data suggest that comorbidity and the tumor burden at the time of transplantation may be useful variables for predicting the outcome in MDS patients receiving myeloablative HCT.

DOI： 10.1111/j.1751-553X.2009.01175.x

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Language：English   Publisher：SPRINGER TOKYO  

DOI： 10.1007/s12185-009-0469-0

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Language：Japanese   Publisher：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

A 60-year-old man was found to have anemia and leukocytosis from a health examination, and diagnosed with primary myelofibrosis (PMF). He was treated with low-dose melphalan but required frequent transfusions of red blood cells, and his splenomegaly enlarged. He received reduced-intensity stem cell transplantation (RIST) from an HLA-identical unrelated donor. The recovery of hematopoiesis was delayed due to the small number of transplanted cells (0.4×108/kg). Splenomegaly and myelofibrosis gradually improved, and transfusion was not necessary 6 months later. He died of pneumonia about 1 year after transplantation. However, this case suggests that RIST is an effective treatment for PMF with giant splenomegaly.

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Language：Japanese   Publisher：Japanese Journal of Cancer and Chemotherapy Publishers Inc.  

A 60-year-old man was found to have anemia and leukocytosis from a health examination, and diagnosed with primary myelofibrosis (PMF). He was treated with low-dose melphalan but required frequent transfusions of red blood cells, and his splenomegaly enlarged. He received reduced-intensity stem cell transplantation (RIST) from an HLA-identical unrelated donor. The recovery of hematopoiesis was delayed due to the small number of transplanted cells (0.4×108/kg). Splenomegaly and myelofibrosis gradually improved, and transfusion was not necessary 6 months later. He died of pneumonia about 1 year after transplantation. However, this case suggests that RIST is an effective treatment for PMF with giant splenomegaly.

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Language：English   Publisher：SPRINGER TOKYO  

We observed the mature granulocytes/monocytes derived from leukemic cells in patients with acute myeloid leukemia who present mixed lineage leukemia gene (MLL). Morphologic observation and fluorescence in situ hybridization analysis (FISH) for chromosome 11q23 abnormality were studied, and a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was done to identify the fusion partners with MLL. The bone marrow cells with FISH signals of MLL showed the cell differentiation of the myeloid and/or monocytic lineages in 4 of 6 AML patients. MLL partner genes were AF6, AF9, ELL, and ENL, respectively. There was no correlation between the fusion partner and the appearance of mature cells derived from MLL clones. RT-PCR showed the fusion between MLL exon 9 or 10 and the partner genes in mature granulocytes/monocytes. These findings suggest that subgroup of leukemia cells with MLL rearrangement has the differentiation potential of leukemic cells and mature granulocytes/monocytes derived from MLL clones may be biologically different from normal mature cells.

DOI： 10.1007/s12185-009-0441-z

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Language：English   Publisher：WILEY-LISS  

The combination of cyclophosphamide and granulocyte-colony stimulating factor (G-CSF) has widely been used to mobilize hematopoietic stem cells (HSCs) for autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Recently, however, alternative approaches such as G-CSF alone or etoposide followed by G-CSF have been investigated. We, therefore, retrospectively analyzed the effects of these mobilization methods on collection yield and disease outcome in ASCT for MM. We reviewed 146 MM patients from whom we intended to collect stem cells. For mobilization, 67, 58, and 21 patients received cyclophosphamide and G-CSF, etoposide and G-CSF, and G-CSF alone (including nonmyelosuppressive chemotherapy followed by G-CSF), respectively. Among them, 136 achieved the target number of HSCs (at least 2 x 10(6)/kg). Lower creatinine and higher albumin levels at diagnosis were significantly associated with successful yield. A lower number of infused HSCs, use of the etoposide for mobilization and high ISS were associated with delayed hematopoietic recovery. The mobilization methods did not significantly affect either the successful collection of more than 2 x 10(6) CD34-positive cells/kg or PFS after ASCT. G-CSF alone was sufficient for stem cell mobilization for a single ASCT. The optimal approach to collect HSCs in MM remains to be elucidated. Am. J. Hematol. 84:809-814, 2009. (C) 2009 Wiley-Liss, Inc.

DOI： 10.1002/ajh.21552

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A 57-year-old woman was diagnosed with acute myeloid leukemia (AML, M5a) with MLL rearrangement in August 2006. Cord blood transplantation (CBT) conditioned with a reduced-intensity regimen was carried out during second complete remission in March 2007. Marrow study on day 28 confirmed complete chimera and disappearance of minimal residual disease by RT-PCR. She complained of left chest pain around day 120. CT scan on day 127 showed left pleural effusion, tumors of the upper mediastinum and spleen, and pericardial effusion. She suddenly died of cardiogenic shock on day 129. Postmortem examination revealed systemic granulocytic sarcomas and infiltration of leukemic cells into the right atrium and epicardium without recurrence of leukemia in blood and marrow.

DOI： 10.11406/rinketsu.50.574

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DOI： 10.1002/ajh.21289

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Language：Japanese   Publisher：The Japanese Society of Hematology  

We report five patients with acute leukemia who underwent allogeneic hematopoietic stem cell transplantation (HSCT) following surgical resection of pulmonary aspergillosis. The patients were three men and two women with a median age of 40 (range, 32 approximately 60). The diagnosis, based on CT imaging, Aspergillus antigen, culture, and histopathology of resected lung specimens, included two proven and three possible pulmonary aspergillosis. Median duration from surgery to HSCT was 2.5 months (range, 1.0 approximately 20). Pre-transplant restrictive-type lung dysfunction was observed in four patients. Antifungal prophylaxis after HSCT was attempted with voriconazole in three patients, amphotericin-B in one patient, and micafungin in one patient. No patients experienced a relapse of pulmonary aspergillosis, although three patients died after HSCT. The causes of death included leukemia relapse in two and hemophagocytic syndrome in one. These results suggest that pre-transplant surgical resection with post-transplant prophylactic antifungal agents seems to be an effective strategy to prevent the relapse of pulmonary aspergillosis in patients with residual disease in the lung before allogeneic HSCT.

DOI： 10.11406/rinketsu.50.430

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We reported 5 patients who developed air-leak syndrome (ALS) including pneumothorax, pneumomediastinum and subcutaneous emphysema after allogeneic stem cell transplantation (SCT). The underlying diseases were AML (n=2), ALL (n=1), MDS (n=1), and CML (n=1). All patients received allogeneic SCT from related donors including 2 donors with HLA mismatch. Total body irradiation was performed as a conditioning regimen in all patients. Late-onset noninfectious pulmonary complications (LONIPC) were detected in all patients before the development of ALS. The interval from diagnosis of LONIPC to onset of ALS was 10-360 days (median, 20 days). Four of 5 patients were treated with corticosteroid for chronic graft-versus-host disease and/or LONIPC. To date, three patients have died of respiratory failure. The others are currently alive and one of these surviving patients is receiving home oxygen treatment. Physicians should be aware of this rare complication following LONIPC, because treatment of ALS is difficult in some patients.

DOI： 10.11406/rinketsu.50.39

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We describe a 44-year-old man with acute myelogenous leukemia who developed thyrotoxicosis after unrelated cord blood transplantation. He complained of fever, general fatigue, tremor and tachycardia on day 63. On examination of thyroid function, free triiodothyronine (23.67 pg/ml) and free thyroxine (5.71 ng/dl) were increased, and thyroid-stimulating hormone (<0.03 microU/ml) was decreased. Antithyroid receptor antibody, antithyroid peroxidase antibody and antithyroglobulin antibody were all negative. The patient was diagnosed as having thyrotoxicosis. His symptoms improved and thyroid function returned to the normal levels within 2 weeks. Thyrotoxicosis is a rare complication, but we should be aware that it may cause idiopathic fever after stem cell transplantation.

DOI： 10.11406/rinketsu.49.1631

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We retrospectively investigated the hematopoietic cell transplantation-specific comorbidity index(HCT-CI)to predict non relapse mortality. Of 127 patients who underwent transplantation between January 2000 and December 2003 with conditioning consisting of total body irradiation, cyclophosphamide and thiotepa, HCT-CI scores were obtained for 83 patients. Median age was 42 years. The sources of stem cells included HLA-identical bone marrow or peripheral blood from sibling(30), HLA-matched bone marrow from unrelated donors(45), and HLA-mismatched bone marrow or peripheral blood from family donors(8). Hematological disease was divided into two groups, standard risk(47)and high risk(36). Standard risk indicates acute leukemia in first or second remission and chronic myelocytic leukemia in first chronic phase, while high risk indicates all other diagnoses. There were 45 patients with moderate or severe pulmonary comorbidities. 55 patients with HCT-CI scores of 2 or less had higher 2-year overall survival than 28 patients with HCT-CI scores of 3 or more(65% vs. 36%, p=0.0009). Although the non relapse mortality rate was not different, HCT-CI scores were a more useful indicator to predict survival in high risk patients than in standard risk patients. Prospective evaluation is warranted to clarify the usefulness of HCT-CI.

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