Search

A 74-year-old woman with a history of pure red cell aplasia and hypogammaglobulinemia developed pneumonia. A urine antigen test and sputum subculture on buffered charcoal yeast extract (BCYE)α agar were positive for Legionella pneumophila. Serological testing identified L. pneumophila serogroup 2. An aerobic blood culture also became positive on day 5; its subculture on BCYEα agar revealed the same pathogen, but that on blood agar revealed Helicobacter cinaedi. We thus diagnosed her with bacteremia caused by both pathogens. Hence, in cases of H. cinaedi bacteremia along with pneumonia, the screening of other pathogens including L. pneumophila is needed.

Peripheral T-cell lymphomas (PTCLs) are a rare and heterogenous group of hematological malignancies involving T or NK cells. PTCLs are generally associated with an aggressive course and poor prognosis. Pralatrexate (PDX) is the first FDA-approved agent for the treatment of refractory/recurrent PTCL. It has single-agent activity against PTCLs; however, oral mucositis represents dose-limiting toxicity in clinical practice. We report on the case of a patient administered with modified THP-COP therapy (pirarubicin [tetrahydropyranyl adriamycin], cyclophosphamide, and prednisone), who had bone or bone marrow as the primary lesion, which was treated successfully with PDX for an extended period of 1 year, with prophylactic use of leucovorin for oral mucositis. The maintenance dose of PDX was 30 mg/m2 IV, over 3 consecutive weeks dosing with a 1-week rest period due to bone marrow suppression. The patient also received leucovorin 5 mg PO 3 times daily from days 2 to 6 after each PDX administration. Disease activity was well controlled, stable, and no oral mucositis was observed over the course of treatment.

Systemic Epstein–Barr virus (EBV)-positive T-cell lymphoproliferative disorders (T-LPD) of childhood is an extremely rare disease characterized by an aggressive clinical course and very poor prognosis. We report an adolescent male with systemic EBV-positive T-LPD of childhood after primary EBV infection, resulting in a fatal clinical course within 9 days, along with autopsy findings. A 19-year-old male without an immunocompromised status presented with an acute onset of high fever, and was hospitalized for persistent fever, vomiting and diarrhea on the 5th day from onset. Laboratory data showed severe thrombocytopenia, increased ferritin level, liver dysfunction, disseminated intravascular coagulation, and anti-EBV-IgM positivity. Peripheral blood smears identified a number of atypical lymphocytes. Bone marrow aspiration revealed many atypical various-sized lymphocytes with apparent nucleoli and hemophagocytosis. Atypical lymphocytes displayed a CD8+ T-cell phenotype with monoclonal rearrangement of T-cell receptors. EBV-encoded RNA was also observed in lymphoid cells by in situ hybridization. The patient received dexamethasone and cyclosporine with no improvement, and died of tumor lysis by leukocytosis on the 9th day from onset.

The purpose of this study was to survey the changes that occur in bolus texture from intake to swallowing during the mastication process for four types of food materials and to identify how texture is related to the number of chews. We recruited 15 young Japanese participants for this study. The subjects were asked to spit the food bolus just before swallowing when eating four different foods: cracker, boiled rice, hard gelatine gel, and soft gelatine gel. Three physical properties (hardness, adhesiveness, and cohesiveness) were measured in the bolus after being chewed for 25, 50, 75, 100, and 125% of the normal number of chews. Occlusal force and pressure as well as stimulated whole saliva volume were also measured. Extensive variation in the number of chews existed between subjects, but minimal intra-subject variation was observed. Hardness was observed to decrease, whereas cohesiveness and adhesiveness increased in a chew-dependent manner for the cracker, soft gelatine gel, and hard gelatine gel, but not boiled rice. Bolus texture appears to be largely related to the number of chews. Hardness also tended to be influenced by occlusion. The adhesiveness and hardness of the boiled rice were also greatly influenced by saliva volume and occlusal force, respectively. Hardness is an important rheological factor in food bolus texture and likely plays a significant role in determining the appropriate number of chews. Adhesiveness and cohesiveness appear to be secondary factors in this process. Practical applications We propose a model of oral processing for application in determining the appropriate number of chews for an individual. Hardness appears to be an important rheological factor in food bolus texture, with adhesiveness and cohesiveness being secondary aspects. When food is hard or difficult to swallow, chewing behavior will likely be more influenced by the perception of bolus texture.

The impact of anti-HLA antibodies, except for donor-specific anti-HLA-A, -B, -DRB1 antibodies, on engraftment was retrospectively evaluated in 175 single cord blood transplantations (CBT). Patients and donors had been typed at HLA-A, -B, and -DRB1 antigens, and anti-HLA antibodies had been screened before transplantation to avoid the use of cord blood (CB) units with corresponding antigens. The median age was 59 (range, 17 to 74) years. Overall, 61% were male, 89% had high-risk disease status, 77% received myeloablative conditioning regimens, and over 80% were heavily transfused patients. Sixty-nine of the 175 (39.4%) were positive for anti-HLA antibodies. Thirty-nine patients had antibodies only against HLA-A, -B, or -DRB1, 13 had antibodies only against HLA-C, -DP, -DQ, or -DRB3/4/5, and 17 had antibodies both against HLA-C, -DP, -DQ, or -DRB3/4/5 and against HLA-A, -B, or -DRB1. Because CB units had not been typed at HLA-C, -DP, -DQ, or -DRB3/4/5, it was possible that antibodies against them were unrecognized donor-specific antibodies. Patients with antibodies only against HLA-A, -B, or -DRB1 showed comparable neutrophil engraftment rates to those without antibodies (89.7% versus 83%, P = .65), whereas patients having antibodies against C, DP, DQ, or -DRB3/4/5 showed lower engraftment rate (66.7%, P = .12), which became statistically significant in a subgroup of HLA-mismatched donor-recipient pairs (50%, P = .01). Our results demonstrated that the presence of donor nonspecific anti-HLA-A, -B, -DRB1 antibodies had no significant influence on engraftment, whereas anti-HLA-C, -DP, -DQ, or -DRB3/4/5 antibodies adversely affect engraftment, possibly because of unrecognized donor-specific anti-HLA antibodies against them, especially in HLA-mismatched CBT.

The purpose of this study was to survey the changes that occur in bolus texture from intake to swallowing during the mastication process for four types of food materials and to identify how texture is related to the number of chews. We recruited 15 young Japanese participants for this study. The subjects were asked to spit the food bolus just before swallowing when eating four different foods: cracker, boiled rice, hard gelatine gel, and soft gelatine gel. Three physical properties (hardness, adhesiveness, and cohesiveness) were measured in the bolus after being chewed for 25, 50, 75, 100, and 125% of the normal number of chews. Occlusal force and pressure as well as stimulated whole saliva volume were also measured. Extensive variation in the number of chews existed between subjects, but minimal intra-subject variation was observed. Hardness was observed to decrease, whereas cohesiveness and adhesiveness increased in a chew-dependent manner for the cracker, soft gelatine gel, and hard gelatine gel, but not boiled rice. Bolus texture appears to be largely related to the number of chews. Hardness also tended to be influenced by occlusion. The adhesiveness and hardness of the boiled rice were also greatly influenced by saliva volume and occlusal force, respectively. Hardness is an important rheological factor in food bolus texture and likely plays a significant role in determining the appropriate number of chews. Adhesiveness and cohesiveness appear to be secondary factors in this process.We propose a model of oral processing for application in determining the appropriate number of chews for an individual. Hardness appears to be an important rheological factor in food bolus texture, with adhesiveness and cohesiveness being secondary aspects. When food is hard or difficult to swallow, chewing behavior will likely be more influenced by the perception of bolus texture.

BACKGROUND: The prognosis of chronic myeloid leukemia (CML) in advanced stages (accelerated phase, AP or blast crisis, BC) is still extremely poor even with tyrosine kinase inhibitors (TKIs) and allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for them. METHOD: Using our database, we retrospectively collected CML patients transplanted at Toranomon Hospital between June 2004 and March 2014, after the introduction of TKIs in Japan. RESULT: Twenty-nine consecutive patients were extracted. The median age was 52 years (range; 16-70). The disease status at diagnosis was chronic phase (CP, n=11), accelerated phase (AP, n=5) and blast crisis (BC, n=13). All the patients were treated with TKIs before transplantation, including imatinib (n=15), nilotinib (n=1), dasatinib (n=6), imatinib/dasatinib (n=4), nilotinib/dasatinib (n=1) and imatinib/nilotinib/dasatinib (n=2). All the 11 patients in CP at diagnosis progressed into AP/BC in their course and only 3 patients achieved second CP (MinorCyR, n=1; PCyR, n=1; MMR, n=1) at transplantation. On the other hand, 11 of 18 patients in AP/BC at diagnosis achieved CP (MinorCyR, n=1; PCyR, n=4; CCyR, n=3; MMR, n=3) at transplantation and the remaining 7 patients did not achieve CHR (Fig. 1). The median HCT-CI and EBMT score at transplantation was 2 (range, 0-5) and 5 (range, 0-7), respectively. Additional cytogenetic abnormalities developed until transplantation in 8 of 11 patients (73%) in CP at diagnosis and in 11 of 18 (61%) in AP/BC at diagnosis. Point mutations in ABL gene were detected in 9 of 20 patients (45%) in their course. Four of 7 patients (57%) in CP at diagnosis had ABL mutations, including T315I (n=1), E255K (n=2) and L359C (n=1). Five of 13 (38%) in AP/BC at diagnosis had ABL mutations, including T315I (n=4) and V299L (n=1). Overall, 14 of 29 (48%) patients underwent transplantation in CP stage (MinorCyR, n=2; PCyR, n=5; CCyR, n=3; MMR, n=4). The donors were related PBSC (n=6), unrelated BM (n=4) or unrelated CB (n=19). The conditioning regimens were myeloablative in 20 patients and reduced-intensity in 9. Twenty-seven patients achieved neutrophil engraftment at a median day of 19 (range, 10-34). The cumulative incidence of neutrophil engraftment was 93.1% at day 42 (patients engrafted, n=27; dead before day 19, n=2). At 3 years, the cumulative incidence of relapse and non-relapse mortality was 32.3% and 14.0%, respectively. In 15 patients who did not achieve CP before transplantation, 11 patients (73.3%) achieved CR after transplantation. With a median follow-up of survivors of 1144 days (range, 127-3705), overall survival (OS) and event free survival (EFS) at 3 years was 63.2% and 56.3%, respectively. In univariate analysis, age ( Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

A 65-year-old man was diagnosed with leukocytosis in a routine medical examination. Further laboratory examinations showed increased LDH and sIL-2R levels in the serum. There was no evidence of infiltrative lesions or organomegaly. Bone marrow aspiration revealed many atypical small-sized lymphocytes without apparent nucleoli. Flow cytometric analysis of atypical lymphocytes was positive for T-cell markers, and chromosome analysis showed a normal karyotype. He was diagnosed with the small cell variant of T-PLL. Approximately 34 months later, having received no treatment, his cervical lymph nodes increased in size and number, and his white blood cell count, LDH and sIL-2R levels also rapidly increased. He was then admitted to our hospital. Bone marrow aspiration and cervical lymph node biopsy revealed complex chromosome abnormalities including inv(14)(q11;q32). Computed tomography showed swollen lymph nodes all over his body and hepatosplenomegaly. On the fourth hospital day, spontaneous splenic rupture occurred. Transcatheter arterial embolization was unsuccessful and the patient died. We report this case with rare autopsy findings.

Early central nervous system (CNS) complications have been associated with significant morbidity and mortality after allogeneic stem cell transplantation (Allo-SCT). However, the incidence, etiology and clinical characteristics of early CNS complications have not been well understood. Moreover, the impact of stem cell sources on early CNS complications remains to be determined. To address these issues, we retrospectively reviewed the medical record of 723 consecutive patients who underwent first Allo-SCT at Toranomon Hospital between 2006 and 2013. Early CNS complications were defined as distinct CNS manifestations such as convulsion, change of mental state, defect of short-term memory, or focal motor or sensory symptoms, occurring within 100 days post-transplant. The etiology of CNS complications was determined by clinical, radiologic, or microbiological finding or a combination of these factors. Patients who developed transient consciousness disturbances in septic state or circulatory collapse, had a history of brain surgery, or showed change of mental status at the terminal stage of multiple organ failures, were excluded from CNS complications. CNS relapses of underlying diseases were also excluded from this analysis. Their median age was 56 years (range, 16-82). Underlying diseases were AML in 360, MDS/MPD in 76, CML in 21, ALL in 82, ATL in 30, HL in 11, NHL in 109, AA in 23 and others in 11. Four hundred ninety-nine (69%) were not in remission at the time of transplant. Three hundred ninety-five patients (54.6%) were conditioned with myeloablative regimens, whereas 328 patients received reduced-intensity regimens. Donor sources consisted of related peripheral blood /bone marrow (BM) (n=101), unrelated BM (166) or cord blood (456). One hundred thirty-seven developed CNS complications on median of 25 (3-89) days post-transplant. Cumulative incidence of CNS complications at 100 days was 19%. The etiology included human herpesvirus 6 (HHV-6) encephalitis/myelitis (n=52), Non HHV-6 viral infections (4), bacterial infections (10), cerebrovascular diseases (18), thrombotic microangiopathy (TMA) / posterior reversible encephalopathy syndrome (PRES) (10), others (3) and unknown causes (40). With median observation period of survivors of 791 (27-2919) days, overall survival at 2 years was 26% in patients who developed CNS complication and was significantly worse than in those who did not develop it (46%, p Early CNS complications are serious concerns leading to inferior survival rate after Allo-SCT. Cord blood recipients are at higher risk for developing CNS complications, particularly of HHV-6 associated. Mechanisms behind them and optimal treatment approaches need to be clarified further to improve outcome. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Relapse after allogeneic stem cell transplantation (Allo-SCT) remains a serious concern and its prognosis is poor. Although 2nd Allo-SCT is the only curative strategy for relapsed patients after Allo-SCT, it is not easy to proceed to 2nd Allo-SCT because of the next donor availability, tumor cell control, and infectious and organ complications. Cord blood (CB) is rapidly available in Japan, but its clinical efficacy is not clearly clarified yet. We retrospectively analyzed the outcome of 85 consecutive 2nd CB recipients with relapsed myeloid malignancies following allogeneic transplantation at Toranomon hospital between January 2005 and March 2014. Their median age was 52 years (range, 19-71). Donors at 1st Allo-SCT were related peripheral blood /bone marrow (BM) (n=24), unrelated BM (27) or CB (34), respectively. Underlying diseases were AML in 79, CML in 4, MDS in 1 and MPD in 1. The median duration of remission after 1st Allo-SCT was 197 (29-2586) days, and the median time from relapse to 2nd CBT and from 1st Allo-SCT to 2nd CBT were 85 (13-1667) days and 370 (56-2680) days, respectively. Twenty-three (27%) received re-induction chemotherapy after relapse after 1st Allo-SCT, whereas 42 (71%) received less intensive chemotherapy (low dose Ara-C and/or hydroxyurea (n=37), gemtuzumab ozogamicin (9), 5-azacitidine (2), and DLI (8)), and 20 (24%) did not receive any treatment. All except 5 patients (94%) were not in remission and 15 (18%) had active infections at the start of conditioning regimen of 2nd CBT. Performance status (PS) at 2nd CBT were 0 in 8 patients, 1 in 30, 2 in 29 and 3 in 7. Thirty-eight patients (45%) were conditioned with myeloablative regimens, whereas 47 patients received reduced-intensity. Calcineurin inhibitor (CI) plus mycophenolate mofetil were used in 36 cases (42%) as GVHD prophylaxis, while CI alone in 49 (58%). All patients received single CB unit with 2.84 (1.85-5.87) x 107/kg median number of total nucleated cell. Sixty-three patients achieved neutrophil recovery on median of 18 (11-39) days post-transplant with a cumulative incidence of 74.1%, and, among 22 who failed to achieve neutrophil recovery, 15 died before engraftment, 4 had early disease progression and 3 were rejected. Fifty-five patient (68%) developed infectious complications due to bacteria (n=42), virus (3), fungus (2) and unknown pathogens (8) within 30 days after 2nd CBT at median of 5 days post-transplant (range, -7 - 21). Median observation period of survivors was 734 (101-3023) days post-transplant. Cumulative incidences of NRM at 100 days and 2 years were 43.5% and 53.6%, respectively. Causes of NRM were Infections (n=19), idiopathic pneumonia syndrome (7), MOF+infections (4), VOD (2), GVHD (2), graft failure (1), and others (11). Higher age, myeloablative-conditioning at 1st Allo-SCT and active infection at 2nd CBT were negatively affected NRM in multivariate analysis. Twenty-seven patients relapsed at a median of 209 (16-2597) days. Cumulative incidences of relapse at 100 days and 2 years were 11.2% and 32.4%, respectively. Overall survival (OS) and progression free survival (PFS) at 2 years were 14.4% and 10.5%, respectively (Figure). Reduced-intensity conditioning at 1st Allo-SCT, younger age ( Although CBT has provided more opportunities of 2nd transplant for relapsed patients, high NRM was noted in this study, resulted in unsatisfactory survival. Multiple factors associated with poor outcome were identified, mostly related to patients' poor background conditions that are not easy to be ameliorated. There were, however, certain population of patients (age Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

MUD 169 0.65 (0.57-0.72) 0.54 (0.45-0.62) 8/10 Loci 31 0.47 (0.29-0.64) 0.40 (0.23-0.57) 0.04 DFS 9/10 Loci 105 0.65 (0.55-0.74) 0.50 (0.40-0.60) Single DQB 18 0.78 (0.51-0.91) 0.72 (0 45-0.87) 0.29 Single C 26 0.56 (0.35-0.73) 0.37 (0.18-0.56) 0.14 Single DQB1 87 0.64 (0.53-0.73) 0.47 (0.36-0.58) 0.42 MUD 169 0.09 (0.04-0.14) 0.13 (0.08-0.19) 8/10 Loci 31 0.07 (0.01-0.19) 0.13 (0.40-0.28) 0.36 aGvHD (Gr 2-4) 9/10 Loci 105 0.14 (0.08-0.22) 0.21 (0.14-0.30)

Introduction In reduced intensity cord blood transplantation (CBT) post transplant immune disorders, including early immune reactions (PIR) and acute GVHD, are potential complications following CBT in adult patients. Such reactions might increase the risk of organ dysfunction, leading to high rates of transplantation-related mortality, particularly in patients who do not respond to primary therapy, which usually consists of steroids. There is no consensus on the optimal salvage treatment of steroid-refractory acute GVHD. Patients and Methods We retrospectively reviewed 388 patients who underwent single-unit reduced intensity cord blood transplantation consecutively from June 2008 to October 2012 at Toranomon Hospital. Patients who were in poor performance status (ECOG PS >3), had active bacterial or fungal infections at the time of conditioning were excluded. The most frequently used conditioning regimens were fludarabine, alkylating agent (melphalan or busulfan) with total body irradination (TBI), tacrolimus plus mycophenolate mofetil for GVHD prophylaxis. Patients in whom acute GVHD developed received methylpredonisolone 1-2 mg/kg per day. If no partial or complete resolution of symptoms occurred, they were considered steroid-refractory and proceeded to salvage treatment with infliximab or ATG. The dose of infliximab was 5 mg/kg/day once weekly for at least 1 course. ATG was given at 1mg/kg/day once weekly for at least 1 course. An observational study compared response and survival rates in all consecutive patients receiving 1 of these 2 treatments. Results 52 patients among this group developed steroid refractory acute GVHD. Infliximab group (n=31) had a higher proportion of patients with grade III-IV GVHD (69% VS 59%, p=0.18). ATG group (n=21) had a higher proportion of patients with stage 3-4 liver GVHD (28% VS 5%, p Both overall response (PR+CR) were significantly higher in the infliximab group compared with the ATG group (54.8% VS 33.3%, p=0.015 ). In multivariate analysis, time from first-line therapy (days Median follow-up of surviving patients from the date of initiation of salvage treatment was 21.6 months (range, 5.5-57.9 months).Overall, median survival was 2 months after salvage treatment (95% CI, 1-3), with 25% of patients surviving at 12 months (95%CI, 11-20). Patients who achieved a CR have better survival rates. GVHD was the main cause of death (50%). When comparing survival according to salvage treatment, better OS with infliximab (33.9% VS 22.8, p=0.08) in univariate analysis was not confirmed in multivariate analysis. In multivariate analysis, grade IV GVHD at steroid refractory GVHD onset (HR,7.1; 95% CI, 1.29-38.7; P=0.021), and gut involvement with bleeding (HR, 7.65; 95% CI, 1.35-43.2; P=0.024) were significantly associated with worse survival. Conclusion We conclude that infliximab has more activity than ATG in the treatment of severe steroid-refractory GVHD, and earlier initiation of salvage therapy may give better response. But outcomes remain poor. New methods to prevent and treat GVHD are needed. Disclosures: No relevant conflicts of interest to declare.

Introduction Although cord blood transplantation (CBT) using reduced-intensity regimens has emerged as an effective therapy for elderly or patients with comorbidities, high relapse rate and non-relapse mortality (NRM) still remain to be resolved. Tointensify antitumor effects without increasing NRM, we have conducted a pilot study of a novel reduced-toxicity myeloablative conditioning for CBT in our institute. Methods The conditioning consisted of intravenous busulfan 12.8 mg/kg, fludarabine 180 mg/m2 and melphalan 80 mg/m2 followed by single CBT. Fifty-one patients with myeloid malignancies not in remission were included in this study between June 2007 and November 2012. All patients provided written informed consent, andmedical records were retrospectively reviewed. Results Their median age was 59 years (range, 19-70), with a median HCT-CI score of 3 (0-6). Underlying diseases were AML in 44, MDS (RAEB-2) in 3, and CML (AP/BC) in 4. All patients were not in remission including primary induction failure (n=19), relapse 1 (14), relapse>2 (7), and untreated (11). Tacrolimus (TAC) plus mycophenolate mofetil were used in 38 cases as GVHD prophylaxis, while TAC alone in 13. All patients received single cord blood unit with 2-mismatches (MM) to the recipient (n=47) and 1-MM (4). The median number of total nucleated cell and CD34+ cells infused at cryopreservation was 2.61 (range, 1.67-5.09) x 107/kg and 0.94 (range, 0.28-2.97) x 105/kg, respectively. Median observation period of survivors was 18.3 (range, 9-75.5) months. Overall survival (OS) and disease free survival (DFS) at 2 years were 62.4% and 55.1%, respectively (Figure 1). Eleven patients relapsed at a median of 5.2 months (range; 0.5-26.7). Cumulative incidences of relapse at 100 days and 2 years were 7.8% and 20.1%, respectively. Cumulative incidences of NRM at 100 days and 2 years were 11.8% and 21.7%, respectively. Causes of NRM were Infection (n=8), GVHD (2) and idiopathic pneumonia syndrome (1). Forty-six out of 51 achieved neutrophil engraftment at median of 19.5 days (range, 13-38) post-transplant, with a cumulative incidence of 90.2%. All patients who achieved engraftment showed complete remission with complete donor chimerism in bone marrow analysis performed at around 30 days post-transplant. Among 5 who failed to achieve neutrophil recovery, 3 experienced early disease progression and 2 died before engraftment, while no patients developed graft rejection. Cumulative incidence of grade II-IV and III-IV acute GVHD were 52.9% and 13.7%, respectively. Of the 42 patients who achieved engraftment and survived longer than 100 days post-transplant, 13 developed limited type of chronic GVHD, and 5 developed extensive type. Conclusion This study demonstrated that the novel conditioning regimen using full-dose busulfan and melphalan for CBT provides reliable engraftment without graft rejection and high OS and DFS rates without increasing NRM, even for relatively higher age population with myeloid malignancies not in remission. The promising results using the regimen deserve further evaluation in a multicenter prospective study. Disclosures: No relevant conflicts of interest to declare.