Feasibility of the imatinib stop study in the Japanese clinical setting: delightedly overcome CML expert stop TKI trial (DOMEST Trial).

BACKGROUND: Treatment-free remission (TFR), the ability to maintain a molecular response (MR), occurs in approximately 50% of patients with chronic myelogenous leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). METHODS: A multicenter phase 2 trial (Delightedly Overcome CML Expert Stop TKI Trial: DOMEST Trial) was conducted to test the safety and efficacy of discontinuing imatinib. Patients with CML with a sustained MR of 4.0 or MR4.0-equivalent for at least 2 years and confirmed MR4.0 at the beginning of the study were enrolled. In the TFR phase, the international scale (IS) was regularly monitored by IS-PCR testing. Molecular recurrence was defined as the loss of MR4.0. Recurrent patients were immediately treated with dasatinib or other TKIs including imatinib. RESULTS: Of 110 enrolled patients, 99 were evaluable. The median time from diagnosis to discontinuation of imatinib was 103 months, and the median duration of imatinib therapy was 100 months. Molecular recurrence-free survival rates were 69.6%, 68.6% and 64.3% at 6, 12, and 24 months, respectively. After discontinuation of imatinib therapy, 26 patients showed molecular recurrence, and 25 re-achieved deep MR after dasatinib treatment. Molecular response MR4.0 was achieved in 23 patients within 6 months and 25 patients within 12 months. Multivariate analysis revealed that a longer time from diagnosis to discontinuation of imatinib therapy (p = 0.0002) and long duration of imatinib therapy (p = 0.0029) predicted a favorable prognosis. CONCLUSIONS: This DOMEST Trial showed the feasibility of TKI discontinuation in a Japanese clinical setting.

High Incidence of Afebrile Bloodstream Infection Detected by Surveillance Blood Culture in Patients on Corticosteroid Therapy after Allogeneic Hematopoietic Stem Cell Transplantation.

Bloodstream infections (BSI) are still important complications after allogeneic hematopoietic stem cell transplantation (allo-SCT). Patients who are receiving corticosteroid therapy can develop BSI without fever. The utility of surveillance blood cultures in these situations is controversial. We retrospectively analyzed 74 patients who received a corticosteroid consisting of ≥.5 mg/kg prednisolone or equivalent after allo-SCT. In principle, we performed surveillance blood culture weekly for these patients. Sixteen patients (21.6%) developed definite BSI. In a multivariate analysis, a myeloablative conditioning regimen, high-risk disease status at allo-SCT, and the presence of a central venous catheter at the initiation of corticosteroid therapy were identified as independent significant risk factors for the development of definite BSI. At the first definite BSI episode, 7 patients (46.7%) were afebrile and diagnosed by surveillance blood culture. However, 6 of these 7 afebrile patients showed various signs that could be attributed to infection at the time of positive blood culture. In conclusion, patients receiving corticosteroid therapy after allo-SCT frequently develop afebrile BSI. Although surveillance blood culture might be beneficial in these situations, it also seems important to not miss the signs of BSI, even when patients are afebrile.

Meta-analysis and meta-regression analysis to compare the outcomes of chemotherapy for T- and B-lineage acute lymphoblastic leukemia (ALL): the use of dexamethasone, L-asparaginase, and/or methotrexate may improve the outcome of T-lineage ALL.

The effects of intensive regimens and the roles of drugs used might differ between T- and B-lineage acute lymphoblastic leukemia (ALL). We performed a literature search for clinical studies published from January 1998 to March 2013. Studies were eligible for inclusion in the analyses if they included more than 80 patients with adult ALL who were treated with a uniform regimen and compared T- and B-lineage ALL. Studies that included only adolescent or elderly patients were excluded. We identified 11 clinical studies, which included a total of 381 and 1366 patients with T- and B-lineage ALL, respectively, and performed meta-analyses using the selected studies. Nine studies included patients with Philadelphia chromosome-positive (Ph+) ALL. A meta-analysis using the random-effect model demonstrated superior survival in patients with T-lineage ALL compared to those with B-lineage ALL (hazard ratio 1.78, 95 % confidence interval 1.50-2.11), though the inclusion of patients with Ph+ ALL in B-lineage ALL must have influenced this result strongly. We performed meta-regression analyses, adjusted according to whether or not patients with Ph+ ALL were included in each study. Use of dexamethasone (Dex), higher dose of methotrexate (MTX), and higher dose of L-asparaginase (L-asp) were associated with a significant trend toward a better outcome in T-lineage ALL. A meta-regression analysis including Dex and the dose of L-asp or MTX together as covariates showed that these factors were independently significant. In conclusion, the use of Dex and high-dose L-asp or MTX may improve the outcome of T-lineage ALL. This hypothesis should be tested in a prospective study including only patients with Ph-negative ALL.

Significance of a positive Clostridium difficile toxin test after hematopoietic stem cell transplantation.

Patients with hematological malignancies show a high prevalence of asymptomatic colonization with Clostridium difficile (CD colonization). Therefore, it is difficult to distinguish CD colonization with diarrhea induced by a conditioning regimen from true Clostridium difficile infection (CDI) in hematopoietic stem cell transplantation (HSCT) recipients. We retrospectively analyzed 308 consecutive patients who underwent a CD toxin A/B enzyme immunoassay test for diarrhea within 100 d after HSCT from November 2007 to May 2014. Thirty patients (9.7%) had positive CD toxin results, and 11 of these had positive results in subsequent tests after an initial negative result. Allogeneic HSCT, total body irradiation, stem cell source, acute leukemia, and the duration of neutropenia were significantly correlated with positive CD toxin results. In a logistic regression model, allogeneic HSCT was identified as a significant risk factor (odds ratio 18.6, p < 0.01). In an analysis limited to within 30 d after the conditioning regimen, the duration of neutropenia was the sole risk factor (odds ratio 10.4, p < 0.01). There were no distinctive clinical features for CDI, including the onset or duration of diarrhea. In conclusion, although CDI may be overdiagnosed in HSCT recipients, it is difficult to clinically distinguish between CDI and CD colonization.

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.

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.

Association between serum high-molecular-weight adiponectin level and the severity of chronic graft-versus-host disease in allogeneic stem cell transplantation recipients.

Recently, a growing body of evidence has suggested that adiponectin, which is secreted by adipose tissues, plays a critical role in obesity-related and autoimmune diseases. We compared the concentrations of adiponectin among 26 normal subjects and 34 allogeneic stem cell transplantation recipients. The concentrations of adiponectin were significantly higher in recipients with chronic graft-versus-host disease (cGVHD) than those in subjects without cGVHD (21.7 ± 11.0 vs 9.1 ± 6.1 µg/mL in females, P < .001; and 10.1 ± 6.8 vs 4.3 ± 2.9 µg/mL in males, P = .003). Multivariate analysis revealed that a higher concentration of adiponectin was associated with female sex (ß-coefficient 8.2, P < .0001) and the severity of cGVHD (ß-coefficient 6.6, 12.7, and 15.6, P < .01, each for mild, moderate, and severe cGVHD, respectively). In addition, adiponectin levels increased as cGVHD progressed, decreased as cGVHD improved, and did not change with stable cGVHD. In conclusion, adiponectin was associated with the severity of cGVHD and might play a role in the pathophysiology of cGVHD.

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.

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.

Renal Medullary Angiitis Associated with Cutaneous Leukocytoclastic Vasculitis: A Case Report.

Renal medullary angiitis is characterized by interstitial hemorrhaging in the medulla with neutrophil infiltration. An 81-year-old man presented with a fever, kidney dysfunction, and purpura of the legs, which was diagnosed as leukocytoclastic vasculitis. Proteinase 3 antineutrophil cytoplasmic antibodies were weakly positive. A kidney biopsy showed severe tubulointerstitial hemorrhaging with neutrophilic infiltration in the perivascular areas surrounding the vasa recta in the medulla without crescent formation in the glomeruli. An immunofluorescence analysis was negative, and electron microscopy revealed no immune-dense deposits, ruling out immunoglobulin A vasculitis. Intravenous methylprednisolone for three days and plasma exchange followed by oral prednisolone improved his general condition.

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.

Clinical course of patients with aplastic anemia or myelodysplastic syndrome associated with persistent neutropenia.

Patients with aplastic anemia (AA) or myelodysplastic syndrome (MDS) often have persistent severe neutropenia and are susceptible to infectious complications. We retrospectively reviewed the clinical course of patients with AA or MDS who had neutropenia (neutrophil count < 500/µl) for more than 25 days. A total of 46 patients, 11 with AA and 35 with MDS, were included. Twenty-three patients had infectious events (IE), and the cumulative incidence of IE was 30% at 6 months and 51% at 1 year. The cumulative incidence of IE was 67% at 1 year in 30 patients who experienced very severe neutropenia of less than 200/µl. Overall survival in all patients was 76% at 6 months and 65% at 1 year. In a multivariate analysis, male sex, underlying diseases, and a neutrophil count of less than 200/µl as a time-dependent covariate significantly affected IE. In analyses that excluded patients with AA, male sex was the only factor. In conclusion, severe neutropenia was significantly associated with IE in patients with AA or MDS, and IE might be lethal. When we only considered patients with MDS, the neutrophil count alone could not be used to predict the prognosis.

Retrospective evaluation of the area over the neutrophil curve index to predict early infection in hematopoietic stem cell transplantation recipients.

We investigated the impact of neutropenia on the development of early bloodstream and pulmonary infections in hematopoietic stem cell transplantation (HSCT) recipients, and evaluated the utility of an index (D-index) that reflects both the intensity and duration of neutropenia. Fifty-eight patients (23 autologous, 35 allogeneic HSCT recipients) were enrolled in this retrospective study. The D-index was defined as the area over the neutrophil curve during neutropenia. We also evaluated the utility of the cumulative D-index from the start of neutropenia until the development of infection (c-D-index), which may enable real-time assessment of the risk for infection. The patients showed 12 and 7 episodes of bloodstream and pulmonary infection, respectively. The D-index, days of neutropenia (<500/microL) and days of profound neutropenia (<100/microL) had at least a nearly significant impact on the development of both bloodstream and pulmonary infections. On the other hand, the c-D-index, cumulative days of neutropenia, and cumulative days of profound neutropenia significantly affected pulmonary infection, but not bloodstream infection. The c-D-index had a high negative predictive value of 97.4% for pulmonary infection with a cutoff of 5500, but the area under the receiver operating characteristic curve was similar to that of the cumulative days of neutropenia and profound neutropenia. Our results showed that although the c-D-index may be useful for identifying patients who are at low risk for early pulmonary infection after HSCT, its performance was similar to that of the simple duration of neutropenia.

Prediction of infectious events by high-sensitivity C-reactive protein level before undergoing chemotherapy for acute myeloid leukaemia.

We retrospectively evaluated the serum high-sensitivity C-reactive protein (CRP) level before chemotherapy for the prediction of infectious events during neutropenia in patients with acute myeloid leukaemia. Thirty-eight patients who underwent first induction chemotherapy and 37 patients who underwent first consolidation chemotherapy were analyzed separately. A receiver-operating characteristic (ROC) curve revealed that the serum CRP level just before the first consolidation chemotherapy, but not just before the induction chemotherapy, had a significant predictive value for febrile neutropenia (FN) at a cut-off value of 0.19 mg/dl and documented infection (DI) at a cut-off value of 0.26 mg/dl. The high-sensitivity CRP measurement enabled the detection of slight increases in the serum CRP level, which might reflect a minute inflammation by occult infection, and discriminated high-risk patients for infectious events.

Fludarabine, cyclophosphamide, anti-thymocyteglobulin, and low-dose total body irradiation conditioning enables 1-HLA-locus-mismatched hematopoietic stem cell transplantation for very severe aplastic anemia without affecting ovarian function.

Allogeneic hematopoietic stem cell transplantation for severe aplastic anemia from an alternative donor is associated with higher risks of graft rejection and severe graft-versus-host disease. We developed a conditioning regimen consisting of rabbit anti-thymocyte globulin, fludarabine, cyclophosphamide, and low-dose total body irradiation. Two adult female patients with transfusion-dependent very severe aplastic anemia underwent 1-locus mismatched transplantation using this regimen. Both patients achieved stable engraftment and the clinical course thereafter was uneventful with persistently normal ovarian function. This novel conditioning regimen may be suitable for alternative donor transplantation for severe aplastic anemia, especially in young female patients.

Impact of estimated glomerular filtration rate based on plasma cystatin C and serum creatinine levels before allogeneic hematopoietic cell transplantation.

BACKGROUND: No standard method for measuring renal function has been established in allogeneic hematopoietic cell transplantation (allo-HCT). METHODS: We retrospectively analyzed 80 patients with hematological diseases who underwent allo-HCT at our center. We assessed renal function using creatinine clearance (Ccr), estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcre), eGFR based on cystatin C (eGFRcys), and the average of eGFRcre and eGFRcys (eGFRave). We then evaluated the impact of pre-transplant renal function on the exacerbation of renal function and non-relapse mortality after transplantation. RESULTS: There was a significant correlation between Ccr and eGFRcre, eGFRcys, and eGFRave. eGFRave best predicted the exacerbation of renal function according to the area under the receiver-operating characteristic curve. The cumulative incidence of renal function exacerbation at 1 year was higher in the lower eGFRave group (<90 ml/min/1.73 m2) than in the higher eGFRave group (≥90 ml/min/1.73 m2; 0.85 vs. 0.39, p < 0.001), which was confirmed by a multivariate analysis (HR 2.75, p = 0.001). A lower eGFRave value was a marginally significant factor for non-relapse mortality (HR 3.29, p = 0.076). CONCLUSION: Among the four parameters, eGFRave best predicted the exacerbation of renal function in allo-HCT. Further, the marginal association between low eGFRave and high non-relapse mortality warrants further study in a prospective study in allo-HCT.

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.

[Appearance of central nervous system lupus during corticosteroid therapy and warfarinization in a patient with pure red cell aplasia and antiphospholipid syndrome].

A 48-year-old woman presented to our hospital with epigastralgia and erythema on the left dorsalis pedis. Her medical history included deep venous thrombosis three months prior to admission to our hospital. Upon admission it was determined that she had severe anemia (hemoglobin level 4.6 g/dl). Bone marrow analysis indicated a markedly decreased number of erythroid progenitor cells. A skin biopsy specimen of the erythema revealed microthrombus. Anticardiolipin-beta2GPI antibody and lupus anticoagulant were positive. The patient was diagnosed with pure red cell aplasia (PRCA) and antiphospholipid syndrome (APS). After steroid pulse therapy and warfarinization, her anemia and purpura improved. Three months later she developed depression with positive anti-ribosomal P protein antibody that was indicative of central nervous system lupus. Although her psychometric condition did not respond to steroid pulse therapy, improvement was seen after she received three courses of cyclophosphamide pulse therapy. We report a rare case of CNS lupus that developed during corticosteroid therapy and warfarinization in a patient with PRCA and APS.

Impact of D-index and L-index on pulmonary infection in induction chemotherapy for acute lymphoblastic leukemia and lymphoblastic lymphoma.

OBJECTIVES: The D-index and the L-index, calculated as the area over the neutrophil and lymphocyte curves, respectively, reflect both the intensity and duration of cytopenia. We, retrospectively, investigated the impact of these indexes on pulmonary infection (PI) in induction chemotherapy for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). METHODS: We included 92 patients (ALL 83, LBL 9) from two institutions. We calculated the D-index and cumulative D-index until the development of PI (c-D-index), which enables real-time risk assessment for infection. We also calculated the L-index (35), defined as the area over the lymphocyte curve during lymphopenia (<700/µl) until day 35 and the cumulative-L-index until the development of PI (c-L-index). RESULTS: Eight patients developed PI on day 20 (median). Two patients were strongly suspected to have bacterial pneumonia, and the others were suspected to have pulmonary fungal infection. The D-index and the L-index (35) in patients with PI were higher than those in patients without PI (7230 ± 4734 vs. 4519 ± 3416, P = 0.041 and 15 458 ± 5243 vs. 8920 ± 5901, P = 0.018), while the c-D-index and the c-L-index were not significantly different. Although the c-L-index did not have predictive value for PI, c-D-index, when treated as a dichotomous variable with a cutoff value of 5589 as determined by a receiver operating characteristic curve analysis, showed a significant difference between two groups (P = 0.045). This association became clearer when we focused on suspected pulmonary fungal infection. DISCUSSION AND CONCLUSION: In induction chemotherapy for ALL/LBL, c-D-index with a cutoff value of 5589 might have predictive value for the development of PI.