A Multidisciplinary Approach to Hip Fractures: Evaluating Outcomes on Mortality and Secondary Hip Fractures.

Fracture liaison services (FLS) have been introduced in Japan and several other countries to reduce medical complications and secondary fractures. We aimed to evaluate the effects of the implementation of an FLS approach on patient outcomes during hospitalization at our hospital and over a 2-year follow-up post-injury. This retrospective cohort study included patients ≥ 60 years admitted to our hospital for hip fragility fractures between October 1, 2016, and July 31, 2020. Patient groups were defined as those treated before (control group, n=238) and after (FLS group, n=196) establishment of the FLS protocol at our institution. The two groups were compared in terms of time to surgery, length of hospital stay, and the incidence of complications after admission, including secondary hip fracture and mortality rates. The follow-up period was 24 months. FLS focuses on early surgery within 48 h of injury and assessing osteoporosis treatment before injury to guide post-discharge anti-osteoporosis medication. FLS reduced the length of hospital stay (p<0.001) and the prevalence of complications after admission (p<0.001), particularly cardiovascular disease, and it increased adherence to anti-osteoporosis medication. These FLS effects resulted in lower secondary hip fracture and mortality rates at 12 and 24 months post-injury. FLS for fragility hip fractures can improve patient outcomes during hospitalization and over a 2-year follow-up period.

Severe adverse events by tyrosine kinase inhibitors decrease survival rates in patients with newly diagnosed chronic-phase chronic myeloid leukemia.

OBJECTIVE: This multicenter cooperative study aimed to analyze the adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs) used as initial treatment for chronic-phase chronic myeloid leukemia (CML-CP) and their impact on outcome. METHODS: We retrospectively evaluated 450 patients with CML-CP who received TKIs between 2004 and 2014. RESULTS: The 5-year overall survival (OS) and event-free survival (EFS) rates were 95.1% and 89.0%, respectively. Patients with comorbidities (46.4%) and aged ≥60 years (50.4%) at diagnosis had significantly inferior OS to those without comorbidities and aged <60. Patients achieved higher rates of major molecular response (MMR) at 6 and 12 months after initial treatment with dasatinib or nilotinib compared to imatinib, but final MMR rates were almost the same. Sixty-six percent of patients required treatment modifications from first-line TKI therapy; the main reasons were AEs (48.4%) and failure (18%). Grade III-IV AEs in first-line TKI therapy were significantly correlated to inferior OS/EFS compared to grade 0-II AEs. CONCLUSION: Although long-term outcomes were similar in CML-CP patients treated with each TKI regardless of first-line TKI selection, severe AEs in first-line TKI therapy decreased their survival rates. Early change in TKIs is recommended, when faced with severe AEs of specific TKIs.

Immunological Analysis and Generation of Dendritic Cells From Lavage Fluid Obtained by Cell-Free and Concentrated Ascites Reinfusion Therapy.

Cell-free and concentrated ascites reinfusion therapy (CART) is an effective treatment for patients with refractory ascites. Cellular components such as cancer cells and blood cells are removed and discarded. The aim of this study was to investigate the alteration of immune cells in lavage fluid and the generation of dendritic cells (DCs) from lavage fluid obtained by CART. Flow cytometry analysis showed a trend toward immunosuppression and impairment in innate immunity in lavage fluid. Immature DCs with downregulation of CD14 and increased antigen-uptake were generated by culturing monocytes obtained from lavage fluid with GM-CSF and IL4. Following the culture with proinflammatory mediators, mature DCs with upregulation of CD83 and potent ability of T cell activation were induced. There were no significant phenotypical or functional differences between these DCs and DCs derived from peripheral blood, indicating lavage fluid might be employed for an alternative cellular source for the generation of DCs.

A Multicenter Retrospective Study of Mogamulizumab Efficacy in Adult T-Cell Leukemia/Lymphoma.

BACKGROUND: Mogamulizumab, a defucosylated humanized monoclonal antibody targeting C-C chemokine receptor 4, recently became available for the treatment of adult T-cell leukemia/lymphoma (ATL). We conducted a multicenter retrospective study of the efficacy of mogamulizumab in ATL treatment in patients on Hokkaido Island, Japan. MATERIALS AND METHODS: A total of 125 patients with ATL treated from January 2010 to December 2014 in 20 hospitals affiliated with the Hokkaido Hematology Study Group were enrolled in the present retrospective study. RESULTS: Of the 125 ATL patients, 62 (46.6%) presented with the acute type, 51 (38.3%) with the lymphoma type, and 12 (9.0%) with the chronic type; the latter group included 7 unfavorable chronic cases. The median age at diagnosis was 68 years (range, 35-86 years). The median survival for those with acute, lymphoma, and unfavorable chronic types was 302, 279, and 921 days, respectively. Advanced age, high lactate dehydrogenase level, poor performance status (3-4), and the existence of B symptoms were unfavorable prognostic factors for overall survival (OS). Survival rate calculated from the day of diagnosis was significantly higher in patients treated with mogamulizumab. The OS of individuals receiving hematopoietic stem cell transplantation (HSCT) was superior to that of the non-HSCT group. The median interval between the last mogamulizumab dose and allogeneic HSCT was 38 days (range, 21-53 days). Of the 22 HSCT recipients who were not treated with mogamulizumab, overall acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD occurred in 12 (54.5%) and 3 (13.6%) patients, respectively. However, overall aGVHD and grade III-IV aGVHD developed in 8 (88.9%) and 3 (33.3%) of the 9 HSCT recipients treated with mogamulizumab, respectively. CONCLUSION: Mogamulizumab improves OS in patients with ATL, although its use in HSCT patients might trigger severe GVHD. Determining the optimal pre-HSCT mogamulizumab treatment regimen is thus a priority.

Long-term survey of survival time, histological transformation, and secondary malignancies in Japanese patients with advanced-stage follicular lymphoma in the rituximab era: Hokkaido Hematology Study Group.

Following the introduction of rituximab, the long-term overall survival (OS) rate of advanced-stage follicular lymphoma (FL) cases was expected to improve after the introduction of rituximab: however, there is a lack of large-scale survey data in Asia due to the relatively low incidence of FL. We conducted a retrospective survey to assess the treatment outcomes in patients with newly diagnosed advanced-stage FL in 29 institutions in Hokkaido from January 2001 to December 2010. The total number of patients was 443 (men 47.6%, women 52.4%), with a median age of 55 years (range 20-80 years). Of the cases examined, 42.2% had stage III and 57.8% had stage IV disease. Furthermore, 62.5, 19.7, 9.2, 5.2, and 3.4% had performance statuses of 0, 1, 2, 3, and 4, respectively. The 5-year OS was 91.2%, and no survival plateau was observed. Seventeen patients experienced secondary malignancies (six hematological diseases and 11 solid cancers; 5-year probability, 4.2%). Eighteen patients experienced transformation (5-year probability, 4.5%). The overall survival at 5 years after therapy for transformation was 50%. Before the introduction of rituximab, the 5- to 10-year OS of advanced-stage FL patients in Japan was reported to be about 30-60%. Although these data are limited, improvement in OS has been observed in Japan during the rituximab era.

Risk factor analysis of non-Hodgkin lymphoma-associated haemophagocytic syndromes: a multicentre study.

Haemophagocytic syndrome is often associated with malignant lymphoma; however, few studies have examined lymphoma-associated haemophagocytic syndrome (LAHS). A total of 1239 patients with non-Hodgkin lymphoma were analysed at 12 institutions in Hokkaido prefecture between January 2007 and December 2011 to assess the incidence, prognosis and risk factors of LAHS. The cumulative incidence rate of LAHS was 2·8% (35/1239). Overall survival (OS) in patients with LAHS was significantly inferior to those without LAHS (3-year OS: 35·6 vs. 59·0% respectively, P < 0·0001). The cumulative incidence of LAHS was higher in patients with T/Natural Killer (NK)-cell lymphoma than in those with B-cell lymphoma (8·2 vs. 1·8% respectively, P < 0·0001). The characteristics of patients with and without early death (within the first 120 d after developing LAHS) were subsequently compared to evaluate the prognostic factor of LAHS. The results obtained showed that the rate of early death after developing LAHS was higher in patients with T/NK-cell lymphoma than in those with B-cell lymphoma (62·5 vs. 10·5%, P = 0·0033). In conclusion, the complication and mortality rates of LAHS were higher in patients with T/NK-cell lymphoma after they developed LAHS than in those with B-cell lymphoma.

Electromyographic study of neck muscle activity according to head position in rugby tackles.

[Purpose] This study examined differences in neck muscle activity in two different head positions during tackles with the aim of contributing to the prevention of sports injuries. [Subjects] The subjects were 28 male high-school rugby players. [Methods] Two tackle positions were considered: a head-up position and a head-down position. Muscle activities of the sternocleidomastoid muscles and the upper, middle, and lower parts of the trapezius muscles were measured. [Results] Muscle activities of the sternocleidomastoid muscles and the right upper trapezius muscle were significantly increased in the head-up position, and the activity of the lower trapezius was significantly increased in the head-down position. [Conclusion] Tackling with the head-up position increases neck muscle activity and stability of the head and the neck.

A retrospective clinical analysis of Japanese patients with peripheral T-cell lymphoma not otherwise specified: Hokkaido Hematology Study Group.

Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) comprises a group of heterogeneous lymphomas that do not fit any other identified PTCL-subgroup and show poor prognosis. To clarify clinical aspects of Japanese PTCL-NOS patients, the Hokkaido Hematology Study Group conducted a multicenter retrospective analysis. The median age of the 107 patients (male 65.4 %) was 67 years. The majority (82.4 %) had stage III/IV disease. Following the international prognostic index, 65.7 % were categorized as high intermediate or high risk. Primary chemotherapy was selected in 96 (90 %) patients, 86 of whom received anthracycline regimens. Sixteen patients received high-dose chemotherapy with autologous stem cell transplantation. Forty-eight (52 %) of the 92 evaluable patients achieved complete remission (CR) or CR/unconfirmed after the primary treatment, in which 22 (46 %) relapsed. The estimated 5-year overall survival (OS) of all patients was 35 %. Three independent risk factors (RFs) associated with OS, bulky disease (hazard ratio HR = 5.324; p = 0.019), age >60 years (HR = 3.015; p = 0.025), and platelet count less than 10 × 10(4)/µL (HR = 3.999; p = 0.036), were identified in a multivariate analysis. Using these three RFs, the OS curves were significantly stratified into three risk groups (low risk, 0 RFs, 3-year-OS 72 %; intermediate risk, one RF, 30 %; high risk, two or three RFs, 0 %; p = 0.0005). These findings may provide valuable information for the management of Japanese PTCL-NOS patients.

Epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies.

Invasive fungal infection (IFI) causes morbidity and mortality among patients with hematological malignancies who receive cytotoxic chemotherapy or hematopoietic stem cell transplantation (HSCT). We evaluated the incidence and treatment outcomes of proven and probable IFI in 22 institutions between 2006 and 2008 following the recent European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) consensus criteria. We analyzed 2,821 patients with hematological malignancies, including 597 who had undergone HSCT; these included patients with acute leukemia (n = 697), myelodysplastic syndrome (n = 284), lymphoma (n = 1465), or multiple myeloma (n = 375). IFIs were diagnosed in 38 (1.3%) patients (18 proven and 20 probable), including 20 patients who underwent HSCT and 18 who received chemotherapy alone; these included patients with aspergillosis (n = 23), candidiasis (n = 6), mucormycosis (n = 6), trichosporonosis (n = 2), and geotrichosis (n = 1). The incidence of IFI was 5.4 % in allogeneic HSCT patients, 0.4 % in autologous HSCT patients, and 0.8 % in patients receiving chemotherapy alone. Eighteen patients with aspergillosis were diagnosed with probable pulmonary IFI as determined by computed tomography scan and positive galactomannan assay. Overall, antifungal targeted therapies resulted in successful outcomes in 60.0 % of patients. IFI-attributable mortality rate was higher in HSCT patients than in those receiving chemotherapy alone, but the difference was not statistically significant.

Outcome of medium-dose VP-16/CY/TBI superior to CY/TBI as a conditioning regimen for allogeneic stem cell transplantation in adult patients with acute lymphoblastic leukemia.

The choice of conditioning regimen before allogeneic stem cell transplantation (SCT) in patients with acute lymphoblastic leukemia (ALL) is important. We retrospectively compared outcomes of medium-dose VP-16/cyclophosphamide/total body irradiation (VP/CY/TBI) regimen and CY/TBI. Five hundred and twenty-nine patients (VP/CY/TBI: n = 35, CY/TBI: n = 494) who met all of the following criteria were compared: first time for SCT, aged 15-59 years; first or second complete remission at SCT; bone marrow or peripheral blood as stem cell source; and HLA phenotypically matched donor. Median age of the patients was 34 years, and patients who received VP/CY/TBI were younger (28 vs. 34 years, P = 0.02). Cumulative incidences of relapse and non-relapse mortality (NRM) were higher for patients who received CY/TBI (P = 0.01 for relapse, P < 0.01 for NRM). After a median follow-up period of 36.9 months, 5-year overall survival (OS) rates were 82.2% in the VP/CY/TBI group and 55.2% in the CY/TBI group. OS, and disease-free survival (DFS) in the VP/CY/TBI group were shown to be significantly better by multivariate analysis [hazard ratio: 0.21 (95% confidence interval: 0.06-0.49) for DFS, hazard ratio: 0.25 (95% confidence interval: 0.08-0.59) for OS]. VP/CY/TBI was associated with a lower relapse rate and no increase in NRM, resulting in better survival than that in CY/TBI for adult ALL patients.

A case of idiopathic systemic capillary leak syndrome with high serum levels of G-CSF on exacerbation.

Systemic capillary leak syndrome (SCLS) is a life-threatening disorder which presents with periodic episodes of hypovolemic shock, due to plasma leakage to the extra-vascular space reflected by accompanying hypoalbuminemia, hemoconcentration and edema often with associated monoclonal gammopathy. We describe a 28-year-old woman with SCLS who required aggressive fluid resuscitation and was successfully treated with corticosteroid, terbutaline, and theophylline. At exacerbation, the levels of serum granulocyte colony-stimulating factor (G-CSF) were increased. Thus, G-CSF might play an important role and can be a useful biomarker for the severity of attacks in SCLS.

Clinical significance of minimal residual disease in adult acute lymphoblastic leukemia.

Monitoring minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) is a useful way for assessing treatment response and relapse. We studied the value of MRD and showed a correlation with relapse for 34 adult patients with ALL. MRD was evaluated by real-time quantitative polymerase chain reaction (RQ-PCR) with probes derived from fusion chimeric genes (BCR/ABL) (n = 12) or PCR-based detection of clonal immunoglobulin and T cell receptor gene rearrangements (n = 16), or both (n = 6). We analyzed 27 of the 34 patients who could be examined for MRD on day 100 after induction therapy. The overall survival (OS) rate (45.0%) and relapse-free survival (RFS) rate (40.0%) at 2 years in complete remission (CR) patients with MRD level ≥ 10⁻³ (n = 12) were significantly lower than those in CR patients with MRD level <10(-3) (n = 15) (OS rate 79.0%, RFS rate 79.4%) (log-rank test, P = 0.017 and 0.0007). We also applied multicolor flow cytometry for comparison with MRD results analyzed by PCR methods. The comparison of results obtained in 27 follow-up samples showed consistency in 17 samples (63.0%) (P = 0.057). MRD analysis on day 100 is important for treatment decision in adult ALL.

Incidence and risk of postherpetic neuralgia after varicella zoster virus infection in hematopoietic cell transplantation recipients: Hokkaido Hematology Study Group.

To assess the incidence of and risk factors associated with postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT) varicella zoster virus (VZV) infection, we conducted a retrospective chart review of 418 consecutive patients who underwent HCT between April 2005 and March 2007. The male/female ratio was 221/197, median age at HCT was 47 years (range: 0-69 years), and autologous/allogeneic/syngeneic HCT ratio was 154/263/1. Seventy-eight patients developed VZV infection after HCT. Sixty-two patients had localized zoster, 11 patients had disseminated zoster (rash like chicken pox), and 4 patients had visceral zoster. All cases were treated with acyclovir (ACV) or valacyclovir (VACV), and there was no VZV infection-related death. Twenty-seven (35%) of the 78 patients with VZV infection suffered PHN after resolution of VZV infection. Multivariate analysis showed that advanced age is the only risk factor in autologous HCT (P = .0075; odds ratio [OR] = 1.14; 95% confidence interval [CI], 0.97-1.33). On the other hand, advanced age (P = .0097; OR = 1.06; 95% CI, 1.01-1.12), male gender (P = .0055; OR = 12.7; 95% CI, 1.61-100.1), and graft-versus-host disease (GVHD) prophylaxis with a tacrolimus-based regimen (P = .0092; OR = 9.56; 95% CI, 1.44-63.3) were associated with increased risk of PHN in allogeneic HCT. This study for the first time clarified the risk of PHN in HCT recipients.

[Evans syndrome associated with idiopathic mixed-type autoimmune hemolytic anemia].

A 60-year-old man was admitted to our hospital with severe anemia and blood findings showed hemolytic anemia. Further serological examination revealed both warm-reactive autoantibody and cold agglutinin against erythrocytes. The cold agglutinin showed a low titer, 1 : 32 at 4 degrees C, and had a high thermal amplitude of 30 degrees C or higher, resulting in sufficient activity for hemolysis. Since no underlying disorders could be detected, the diagnosis was idiopathic mixed-type autoimmune hemolytic anemia. Although thrombocytopenia (Evans syndrome) subsequently appeared, corticosteroid was extremely effective for both anemia and thrombocytopenia. In this report we describe a rare case of Evans syndrome associated with mixed-type autoimmune hemolytic anemia, which had a dramatic response to corticosteroid therapy.

Effects of the mean daily doses of imatinib during the first year on survival of patients with chronic myeloid leukemia in Japan: a study of the Hokkaido Hematology Study Group.

In this study, we retrospectively analyzed 213 Japanese patients with chronic myeloid leukemia (CML) treated with imatinib mesylate. In 150 evaluable patients, mean daily doses were 400 mg or more in 42 patients, 300-400 mg in 42 patients, 200-300 mg in 44 patients and <200 mg in 22 patients. Complete hematologic response was observed in all the 84 patients treated with mean daily doses of 300 mg or more and complete cytogenetic response was achieved in 94.8% of those patients. In comparison with the effects of 300 mg or more, mean daily doses of 200-300 mg led to less complete cytogenetic response (78.6% vs. 94.8%, P < 0.01), shorter complete cytogenetic remission duration (81.3% vs. 95.6% at 24 months, P = 0.01), and lower overall survival (90.0% vs. 98.8% at 36 months, P = 0.03). This study suggests that the mean daily doses of 300 mg (roughly equivalent to 100,000 mg/yr) or more may improve overall survival and that mean daily doses of imatinib during the first year may be one of the prognostic factors for CML in Japan.

Low-dose thalidomide plus low-dose dexamethasone therapy in patients with refractory multiple myeloma.

We report the results of a non-randomized phase II study of low-dose thalidomide plus low-dose dexamethasone therapy in 66 patients with refractory multiple myeloma. The overall response rate (near complete, partial and minimal response) was 63.6%, and progression-free and overall survival periods were 6.2 and 25.4 months. In adverse events, the incidence of peripheral neuropathy and deep vein thrombosis was lower than the data reported in USA and Europe. On the other hand, leukopenia was observed in 41% of patients, including 11% of those with Grade 3. Leukopenia was closely related to pretreatment pancytopenia, especially thrombocytopenia. The incidence of adverse events related to dexamethasone was low. In conclusion, low-dose thalidomide plus low-dose dexamethasone therapy was as effective as high-dose thalidomide plus high-dose dexamethasone therapy in patients with refractory multiple myeloma. Leukopenia is one of the most serious adverse events in Japanese patients, especially in patients with pretreatment pancytopenia.

Effect of granulocyte colony-stimulating factor on IL-12 p40 production during chemotherapy for B-cell lineage non-Hodgkin's lymphoma patients.

Interleukin (IL)-12 is a 70-kDa cytokine comprised of two disulfide-linked proteins (p35 and p40) and is essential for the initiation of effective immune response. Granulocyte-colony stimulating factor (G-CSF) affects the balance in the production of anti-inflammatory cytokines. We investigated the serum IL-12 p40 and IL-12 Mix (p40 and p70) production in 28 patients with B-cell lineage non-Hodgkin's lymphoma (NHL) treated with chemotherapy (e.g., CHOP regimen) with or without G-CSF administration and eight healthy volunteers. We found that serum levels of IL-12 p40 (191.2 +/- 150.0 pg/mL) and IL-12 Mix (277.4 +/- 274.5 pg/mL) in the patients before chemotherapy were higher than those in the healthy volunteers (IL-12 p40: 76.4 +/- 25.3 pg/mL, IL-12 Mix: 48.5 +/- 33.4 pg/mL) (P = 0.04 and 0.02, respectively). Next, we examined the serum IL-12 p40 and IL-12 Mix levels in nine patients receiving chemotherapy with administration of G-CSF (CG group, n = 9) and without G-CSF (C group, n = 9). Serum IL-12 p40 and IL-12 Mix levels were decreased on 10 d after chemotherapy in both groups, and those in CG groups were significantly lower than those in C group. These results indicated that administration of G-CSF decreased serum IL-12 p40 and IL-12 Mix levels. Overall survival (OS) at 24 months was not significantly different in the two groups (58.3% in group C vs. 80.0% in group CG, P = 0.67). However, the survival rate of patients at clinical stages III and IV in CG group (n = 6, 66.0%) was significantly better than that of patients in C group (n = 4, 25.0%) (P = 0.02). Long-term administration of G-CSF appears to influence the survival rate by reducing immunosuppressive IL-12 p40 production.

[Clinical features of a new category, myelodysplastic/myeloproliferative diseases, defined by WHO classification].

The WHO classification published in 2001 defined a new category of hematological disease, myelodysplastic/myeloproliferative diseases (MDS/MPD), that have both myelodysplasia and myeloproliferation at the time of initial presentation. This category consists of four subclasses, chronic myelomonocytic leukemia (CMML), atypical CML(aCML), juvenile chronic myelogenous leukemia and MDS/MPD-unclassifiable (MDS/MPD-u). In order to clarify the clinical features of these diseases, we analyzed clinical data of tentatively diagnosed MDS/MPD cases in the past ten years accumulated from affiliated hospitals. By reviewing the data of each case according to the criteria, we diagnosed 31 cases of MDS/MPD, including 22 cases of CMML, 5 cases of aCML and 4 cases of MDS/MPD-u. Male predominance and high age were common among these three subclasses. The prognosis of CMML was poor compared to other subclasses because of the high incidence of blast crisis. It is noteworthy that blast crisis in CMML exclusively occurred within one year after diagnosis. Young age, a high percentage of blasts in the peripheral blood, splenomegaly, lymphadenopathy and clonal cytogenetic abnormality were associated with blast crisis. It is suggested that there are two subgroups in CMML which differ in disease progression. Thus, these indicators may be useful in deciding the therapeutic strategy including hematopoietic cell transplantation for the high risk subgroup. There were four MDS/MPD cases with a history of preceding hematological diseases, such as aplastic anemia, MDS or malignant lymphoma. Among these, three cases with a long-term history of treatment with metenolone acetate developed CMML. It is suggested that the long-term effect of androgen plays a role in the pathophysiology of CMML.

Minimal residual disease (MRD) monitoring using rearrangement of T-cell receptor and immunoglobulin H gene in the treatment of adult acute lymphoblastic leukemia patients.

We evaluate whether molecular monitoring of minimal residual disease (MRD) using TCR delta (TCRD), TCR gamma (TCRG), and immunoglobulin H (IgH) gene rearrangements in the bone marrow (BM) is correlated with clinical events in ALL patients. The 14 patients enrolled in this study included 6 males and 8 females with a median age of 53 years (range, 25-79 years), and the median duration of follow-up was 417 days (range, 57-617 days). The median WBC count was 11.3 x 10(9)/L at diagnosis. All patients had L2 type ALL. Eleven patients had a monoclonal pattern of IgH (7), TCRD (3) and TCRG (1), and 3 patients had two clonal patterns. Eleven of the 14 patients achieved the first complete remission (CR) after the first induction chemotherapy. We analyzed 9 of 11 CR patients who could be examined immediately after induction chemotherapy (including re-induction therapy). Event-free survival (EFS, 0%) and disease-free survival (DFS, 0%) at 1 year in CR patients with MRD level >or=10(-3) (n = 3) were significantly lower than those in CR patients with MRD level <10(-3) (n = 6) (log-rank test, P = 0.013, 0.013). A lower MRD in BM value after induction chemotherapy was associated significantly with longer survival in the log-rank test. Our data provide evidence that molecular MRD status of BM is a strong predictor of outcome in adult ALL.