Development and validation of a scoring system to predict vasovagal reaction upon whole-blood donation.

BACKGROUND AND OBJECTIVES: Risk factors for vasovagal reaction (VVR) have been extensively studied. With knowledge of the relative importance of these risk factors for VVR, collection staff could take care of blood donors from the same standpoint, leading to improved donor safety. We therefore developed a scoring system to predict VVR, which incorporates registration information. MATERIALS AND METHODS: Pre-syncopal and syncopal symptoms, as well as on- and off-site reactions, are included in this analysis as VVR. We defined the donor status as follows: first-time donors, repeat donors with no history of reaction and repeat donors with a history of reaction. We prepared two datasets: whole-blood donations at a blood donation site in Tokyo between January 2019 and December 2019 were included in training data (n = 361,114), and whole-blood donations between January 2020 and August 2020 were included in testing data (n = 216,211). RESULTS: The most important variable was the donor status, followed by age, estimated blood volume and height. We integrated them into a scoring system. Training and testing datasets were combined (n = 577,325), and VVR rates in groups with scores of 0, 1, 2, 3, 4 and 5 or more were 0.09% (95% CI: 0.081%-0.10%), 0.33% (95% CI: 0.31%-0.36%), 0.87% (95% CI: 0.78%-0.96%), 1.17% (95% CI: 1.05%-1.30%), 2.15% (95% CI: 1.98%-2.32%) and 3.11% (95% CI: 2.90%-3.34%), respectively. CONCLUSION: The scoring system enables staff to significantly predict VVR and may help them to identify donors at increased risk of experiencing syncope, thereby mitigating the negative impact of VVR on donor safety and return by paying close attention to high-risk donors.

Transfusion-associated circulatory overload and high blood pressure: A multicentre retrospective study in Japan.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is an adverse reaction associated with a high risk of mortality. The actual incidence of TACO and hypertension associated with transfusion in Japan is unknown. METHODS: A multicentre retrospective observational study was conducted across 23 institutions during the 1-year period of 2016. Patients were included if they developed TACO or their blood pressure (either systolic or diastolic) increased by at least 30 mmHg during the transfusion. TACO was confirmed by the primary physicians and transfusion medicine teams and recorded in the data on passive surveillance, and additional data were extracted from electronic medical records. RESULTS: In our patient cohort of 31 384 patients who underwent transfusion, the incidence of TACO and hypertension was 0·03% and 0·2%, respectively. However, 43% of the participating institutions didn't report any cases. When comparing risk factors between the TACO and hypertension groups, there were significant differences in comorbidities, such as abnormal findings on chest x-ray. Significant differences between the two groups were observed post-transfusion pulse rate, body temperature and oxygen saturation (P < 0·01). In the group of patients with hypertension, the level of BNP increased significantly after transfusion in 45% (5/11) of the patients. We identified 4 patients in the hypertension group who met the new ISBT's TACO criteria. CONCLUSION: Our study suggests that more attention should be given to TACO in Japan, particularly in terms of improving surveillance systems. For the early diagnosis of TACO, it is crucial to carefully monitor vital signs including blood pressure.

Splenomegaly Negatively Impacts Neutrophil Engraftment in Cord Blood Transplantation.

Delayed neutrophil engraftment (NE) has been reported in cord blood transplantation (CBT) compared with other stem cell transplantation methods. The numbers of total nucleated cells (TNCs), CD34+ cells (generally ≥ 1 × 105/kg), and granulocyte/macrophage colony-forming units (CFU-GM) significantly impact NE. Splenomegaly exerts negative effects on NE, but the appropriate cell dose for the patients with splenomegaly has not yet been determined, especially in CBT. We retrospectively investigated the effect of splenomegaly and number of CD34+ cells infused on NE through the analysis of outcomes of 502 consecutive patients who underwent single CBT for the first time at Toranomon Hospital between 2011 and 2018. Spleen index, Lmax × Hvert (SI Lmax × Hvert), was defined as maximal length at any transverse section, (Lmax) × vertical height (Hvert), and splenomegaly was defined as SI Lmax × Hvert ≥ 115 cm2. Our results show that splenomegaly (hazard ratio [HR], .60; P < .01) and low dose of infused CD34+ cells (HR, .58; P < .01) had significant negative impact on NE, whereas neither CFU-GM dose nor TNC dose had any impact on NE in multivariate analysis. Other factors with a significant negative impact on NE in multivariate analysis were myeloid disease (HR, .62; P < .01), nonremission status at CBT (HR, .71; P < .01), low Eastern Cooperative Oncology Group Performance Status (HR, .68; P < .01), and graft-versus-host disease prophylaxis (other than tacrolimus alone) (HR, .76; P < .01). Without splenomegaly, even patients infused with < .8 × 105/kg CD34+ cells achieved up to 94.3% NE, with the median value observed at 21 days post-CBT. This study shows that splenomegaly has a significant negative impact on NE after CBT. Cord blood units with < .8 × 105/kg CD34+ cells may still be a suitable choice for patients without splenomegaly.

Prognostic Impact of Cytogenetic Evolution on the Outcome of Allogeneic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia in Nonremission: A Single-Institute Analysis of 212 Recipients.

Recent progress in genetic analysis technology has helped researchers understand the pathogenesis of acute myeloid leukemia (AML). Considering this progress, AML karyotype is still one of the most significant prognostic factors that provides risk-adapted treatment approaches. Karyotype changes during treatment have been observed at times, but their prognostic impact is sparse, especially on allogeneic stem cell transplantation (allo-SCT). Here, we retrospectively investigated the effect of chromosomal changes between diagnosis and pretransplantation on the prognosis of allo-SCT by analyzing the outcomes of 212 consecutive patients who underwent allo-SCT for the first time at Toranomon Hospital, Tokyo, Japan, between 2008 and 2018. Cytogenetic abnormalities at diagnosis and pretransplantation were categorized based on the 2017 European Leukemia Net risk stratification. Genetic abnormalities such as FLT3-ITD and NPM1 were not considered in this study due to lack of genetic information in most patients. We defined cytogenetic evolution as chromosomal changes classified from lower category to higher category. Seventeen patients (8%) had cytogenetic evolution between diagnosis and pretransplantation, and they showed a significantly worse relapse rate than those who were categorized in the intermediate group based on the karyotype at diagnosis (3-year confidence interval [CI] of relapse, 57.4% versus 24.9%; P < .01). In multivariate analysis, cytogenetic evolution before allo-SCT had a significant impact on the CI of relapse (hazard ratio [HR], 3.89; CI, 1.75 to 8.67; P < .01), as well as the high score of the hematopoietic cell transplantation-specific comorbidity index (HR, 0.54; CI, 0.31 to 0.94; P = .03), but had no significant impact on overall survival or nonrelapse mortality. These results indicate that cytogenetic evolution has a significant impact after allo-SCT and should be considered during AML treatment.

Released washed platelet concentrates are effective and safe in patients with a history of transfusion reactions.

BACKGROUND: Plasma removal by washing is an effective approach to prevent transfusion reactions by platelet concentrates (PCs). Recently, washed PCs were released by the Japanese Red Cross Society (JRCS). MATERIALS AND METHODS: This retrospective multicenter study evaluated the efficacy and safety of released washed PCs (RWPCs) between September 2016 and January 2017 in Japan. The RWPCs were prepared by washing leukoreduced apheresis PCs with the platelet additive solution, BRS-A, using automated cell processors. RESULTS: Clinical data were obtained from 91 patients and 1210 RWPC transfusions at 50 institutions. The median number of RWPC transfusions per patient was 8 (range, 1-91). RWPCs were used in 94.5% of the patients with a history of recurrent or severe transfusion reactions for preventing such reactions. Responses of RWPCs were evaluated as complete response (91.6%), partial response (8.2%), no-change (0.2%), and progression (0%) and overall response was equal across subgroups divided by patients' profiles. The median corrected count increment (CCI) at 1 and 24 h post-transfusion were 13.5 (range, 1.9-35.4) × 109/L and 3.5 (range, -13 to 53.6) × 109/L, respectively, and median CCI at 24 h was 5.5 (range, -13 to 53.6) × 109/L in patients without risk factors associated with platelet transfusion refractoriness. Transfusion reactions to RWPCs were observed in only nine transfusions (0.7%), all of which were mild allergic reactions. CONCLUSION: This study demonstrated that RWPCs were effective and safe in patients with a history of transfusion reactions. Further prospective studies on efficacy together with cost-benefit analysis in RWPCs are needed.

Successful Treatment of Pulmonary Mucormycosis Caused by Cunninghamella bertholletiae with High-Dose Liposomal Amphotericin B (10 mg/kg/day) Followed by a Lobectomy in Cord Blood Transplant Recipients.

Infection caused by Cunninghamella bertholletiae carries one of the highest mortality rates among mucormycosis, and there are no reported cases that survived from the infection in allogeneic hematopoietic stem cell transplantation recipients occurring before neutrophil engraftment. Here, we present two cases of pulmonary mucormycosis caused by C. bertholletiae occurring before neutrophil engraftment after cord blood transplantation. Both were successfully treated with high-dose liposomal amphotericin B (10 mg/kg/day) combined with micafungin, which was then followed by neutrophil recovery, reduction in immunosuppressive agents, and a subsequent lobectomy. The intensive antifungal therapy immediately administered upon suspicion of mucormycosis greatly suppressed the infection in its early stage and was well tolerated despite its prolonged administration and simultaneous use of nephrotoxic agents after transplantation. Although the synergic effect of micafungin remains unclear, these cases highlight the importance of prompt administration of high-dose lipid polyene when suspecting mucormycosis in highly immunocompromised patients, which enables subsequent diagnostic and therapeutic interventions, resulting in a favorable outcome.

A Novel Reduced-Toxicity Myeloablative Conditioning Regimen Using Full-Dose Busulfan, Fludarabine, and Melphalan for Single Cord Blood Transplantation Provides Durable Engraftment and Remission in Nonremission Myeloid Malignancies.

A pilot study of a novel, reduced-toxicity, myeloablative conditioning regimen using intravenous busulfan 12.8 mg/kg, fludarabine 180 mg/m(2), and melphalan 80 mg/m(2) for single cord blood transplantation (CBT) was conducted at our institution. Fifty-one patients with myeloid malignancies not in remission were included in this study. Their median age was 59 years (range, 19 to 70 years), with a median hematopoietic cell transplantation-specific comorbidity index score of 3. With a median observation period of 39.6 months (range, 24.3 to 90.8 months) among the survivors, overall survival and progression-free survival at 2 years were both 54.9%. Forty-six of 51 achieved neutrophil engraftment at a median of 19.5 days (range, 13 to 38 days) after transplantation, with a cumulative incidence of 90.2%. No patient developed graft rejection in this study. All patients who achieved engraftment showed hematological complete remission with complete donor chimerism. Eleven patients relapsed at a median of 4.9 months (range, .5 to 26.7 months). Cumulative incidences of nonrelapse mortality (NRM) at 100 days and 2 years were 11.8% and 25.5%, respectively. In conclusion, the present results show that the novel conditioning regimen for single CBT provided durable engraftment and remission with acceptable NRM leading to excellent survival, even for a relatively older population with myeloid malignancies not in remission.

Transfusion medicine in practice.

The safety and stability of the supply of blood products must be ensured for appropriate blood transfusion therapy. Various security measures need to be taken and a balanced blood donation system should be maintained by the Japanese Red Cross Society. Based on such a system, each institute needs to establish a proper management protocol and to assure adequate use of blood products, as well as creating measures to deal with adverse events associated with blood transfusion. The system for preventing transfusion errors is particularly essential. For appropriate use of blood products, the "Guideline for the Use of Blood Products" should be followed, and unnecessary use should be avoided. These are prerequisites for error-free treatment of patients. In this educational lecture, major points in performing blood transfusion in clinical practice, such as proper indications for the use of blood products associated with patient conditions or trigger levels, and important points as well as contraindications when using blood products, such as the speed of administration, will be discussed.

Anti-HLA antibodies other than against HLA-A, -B, -DRB1 adversely affect engraftment and nonrelapse mortality in HLA-mismatched single cord blood transplantation: possible implications of unrecognized donor-specific antibodies.

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.

Questionnaire-based survey on chemotherapy-induced anemia.

A questionnaire-based survey on chemotherapy-induced anemia (CIA) in cancer patients was conducted between September and November 2010. The number of patients treated with chemotherapy, rate of blood transfusion, volume of blood transfused, severity of anemia, and factors affecting blood transfusion were analyzed according to the type of cancer, in an attempt to clarify the current status of CIA in Japan. During the survey period, among the eight types of cancer analyzed (breast, lung, stomach, colorectal, liver, gynecologic cancer, urologic cancer, and malignant lymphoma), chemotherapy was given to 5.4-13.6 % (mean 9.2 %) of patients, among whom 1.6-24.0 % (mean 7.5 %) required blood transfusion. The number of units of red blood cells transfused was 3.9-7.3 units (mean 5.9 units) per patient. According to a nationwide patient survey conducted by the Ministry of Health, Labour and Welfare, it is estimated that approximately 146,000 units of red blood cells, which account for 2.2 % of the annual total supply of red blood cell products, are transfused to cancer patients with CIA yearly. In addition, it is estimated that annually approximately 172,000 cancer patients with CIA, accounting for 40 % of patients receiving chemotherapy, have hemoglobin (Hb) levels below 10 g/dL. Possible factors affecting blood transfusion include a history of chemotherapy and radiotherapy, as well as the use of platinum agents. In patients who received red blood cell transfusions, the average Hb level prior to chemotherapy was 9.5 g/dL, and the average lowest Hb level after starting chemotherapy was 6.9 g/dL. By contrast, in patients who did not receive transfusion, these values were 11.6 and 10.4 g/dL, respectively. Furthermore, in all cancer types, almost no red blood cell transfusion was performed in patients with an Hb level of 8.0 g/dL or higher, but also many patients with an Hb level of 6.9 g/dL or lower did not receive red blood cell transfusions. There was no significant difference in the ratio of adverse events following blood transfusion in this survey compared with that in the nationwide survey. The present results demonstrate the strict restriction of red blood cell transfusion to cancer patients with CIA. Therefore, there is a need to consider the use of alternative therapies to allogeneic blood transfusion, such as erythropoiesis-stimulating agents, to increase Hb levels, and consequently improve the quality of life in cancer patients with CIA.

[The current state of transfusion medicine in Japan].

In Japan, transfusion medicine, which is supported by the voluntary blood donation system, is facing a risk of blood shortage. This is due to reduced donations by the younger generation as well as the falling birth rate and the aging of the population, with a consequent increase in the elderly population that depends on blood transfusions for conditions such as cancer and hematological and cardiovascular diseases. Therefore, to guarantee stable provision of blood products, in addition to implementing measures to promote blood donation, healthcare professionals must, as a policy, strictly follow the rules for appropriate use of blood products as defined in the "Criteria for the Use of Blood Products". Additionally, measures such as the use of autologous blood to reduce allogeneic blood usage and the implementation of adequate internal control systems to reduce blood wastage should be considered. Further, although this is not presently covered by the Japanese Health Insurance System, cryoprecipitate or fibrinogen products, which are used as alternative therapies in cases of hypofibrinogenemia due to massive bleeding, are effective not only for reducing the blood transfusion volume, but also for alleviating bleeding in patients. Additionally, the use of erythropoietin to treat chemotherapy-induced anemia is an effective measure to improve patients' quality of life, and its prompt approval by the Health Insurance System is desired.

Lymphocyte Crossmatch Testing or Donor HLA-DP and -DQ Allele Typing Effectiveness in Single Cord Blood Transplantation for Patients With Anti-HLA Antibodies Other Than Against HLA-A, -B, -C, and -DRB1.

Anti-human leukocyte antigen (HLA) antibodies other than those against HLA-A, -B, -C, and DRB1 are a risk factor for engraftment delay and failure, especially in cord blood transplantation (CBT). The primary objective of this study was to assess the impact of the presence of anti-HLA antibodies on CBT and to evaluate the utility of lymphocyte crossmatch testing or additional HLA-DP and -DQ typing of CB units in improving transplant outcomes. We retrospectively assessed the engraftment rates and transplant outcomes of 772 patients who underwent their first CBT at our hospital between 2012 and 2021. Donors were routinely typed for HLA-A, -B, -C, and-DRB1 alleles, and the anti-HLA antibodies of recipients were screened before donor selection in all cases. Among patients who had antibodies against other than HLA-A, -B, -C, and DRB1 (n = 58), lymphocyte crossmatch testing (n = 32) or additional HLA-DP/-DQ alleles typing of CB (n = 15) was performed to avoid the use of units with corresponding alleles. The median patient age was 57 years (16 to 77). Overall, 75.7% had a high-risk disease status at transplantation, 83.5% received myeloablative conditioning regimens, and >80% were heavily transfused. Two hundred twenty-nine of the 772 recipients (29.6%) were positive for anti-HLA antibodies. There were no statistical differences in the number of infused CD34-positive cells between the anti-HLA antibody-positive and the anti-HLA antibody-negative patients. Of the 229 patients with anti-HLA antibodies, 168 (73.3%) had antibodies against HLA-A, -B, -C, and-DRB1 (Group A), whereas 58 (25.3%) had antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5 with or without antibodies against HLA-A, -B, -C, and -DRB1 (Group B). No patients in both Groups A and B exhibited donor-specific anti-HLA antibodies against HLA-A, -B, -C, and -DRB1. The neutrophil engraftment rate was lower in patients with anti-HLA antibodies than in those without antibodies (89.9% versus 94.1%), whereas nonrelapse mortality (NRM) before engraftment was higher in antibody-positive patients (9.6% versus 4.9%). In patients who received 2 or more HLA allele-mismatched CB in the host-versus-graft (HVG) direction (n = 685), the neutrophil engraftment rate was lower in the anti-HLA antibody-positive recipients than in the antibody-negative recipients with significant differences (88.8% versus 93.8%) (P = .049). Similarly, transplant outcomes were worse in the antibody-positive patients with respect to 2-year overall survival (OS) (43.1% versus 52.3%) and NRM (44.0% versus 30.7%) than in the antibody-negative patients. In contrast, the results of Group B were comparable to those of the antibody-negative patients, while those of Group A were statistically worse than the antibody-negative patients in terms of all engraftment rate (88.6%), OS (34.2%), and NRM (49.0%). The presence of anti-HLA antibodies negatively impacts engraftment, NRM, and OS in CBT. However, HLA-DP/-DQ allele typing of CB units or lymphocyte crossmatch testing could be a useful strategy to overcome poor engraftment rates and transplant outcomes, especially in patients with anti-HLA antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5.

A case report of a truncated ABL1 mutation in 2 cases with Philadelphia chromosome-positive B cell precursor acute lymphoblastic leukemia.

Acquired point mutations in the ABL1 gene are widely recognized as a cause of Philadelphia chromosome-positive B cell precursor acute lymphoblastic leukemia (Ph+ B-ALL) that is resistant to tyrosine kinase inhibitors, whereas there are few reports about other types of the ABL1 mutation. Here, we report 2 cases of Ph+ B-ALL gaining a partial deletion type mutation of the ABL1 gene (Δ184-274 mutation), which resulted in truncation of the ABL1 molecule and loss of kinase activity. In both cases, the disease was refractory to multiple agents in the recurrent phase after allogeneic hematopoietic cell transplantation. This is a case report of a truncated ABL1 mutation in 2 patients with Ph+ B-ALL.

Long-term lymphocyte subset number reconstitution is unique but comparable between umbilical cord blood and unrelated bone marrow transplantation.

The number of umbilical cord blood transplantation (U-CBT) procedures has been growing annually, but little research has been done on long-term immune recovery after U-CBT. Infection risk is high in U-CBT recipients, and this can be partially attributed to immature immunocompetent cells in umbilical cord blood. In this study, we analyzed lymphocyte subset (LST) number to determine the long-term recovery timeline. We included 36 U-CBT and 10 unrelated bone marrow transplantation (U-BMT) recipients who survived more than 2 years after transplantation, and followed them for up to 10 years post-transplant. Recovery kinetics in the early phase post-transplant was different for each LST. Recovery of CD19+ B cells was faster after U-CBT than after U-BMT in the first 5 years after transplantation. Although CD4+ T cells increased in the first several months after U-CBT, long-term cell count recovery was impaired in approximately 20% of patients. Thus, although the LST recovery pattern after U-CBT was unique, LST number recovery was statistically comparable between U-CBT and U-BMT past 5 years post-transplantation.

Successful sustained engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with severe aplastic anemia.

We retrospectively analyzed 12 consecutive adult severe aplastic anemia patients who received unrelated umbilical cord blood transplantation after a reduced-intensity conditioning regimen (RI-UCBT). The conditioning regimen consisted of 125 mg/m² fludarabine, 80 mg/m² melphalan, and 4 Gy of total body irradiation. The median infused total nucleated cell number and CD34(+) cell number were 2.50 × 107/kg and 0.76 × 105/kg, respectively. Eleven of the 12 patients achieved primary neutrophil and platelet engraftment. All patients who achieved engraftment had complete hematologic recovery with complete donor chimerism, except for one patient who developed late graft failure 3 years after RI-UCBT. Two of the 12 patients died of idiopathic pneumonia syndrome, and the remaining 10 patients are alive, having survived for a median of 36 months. Our encouraging results indicate that RI-UCBT may become a viable therapeutic option for adult severe aplastic anemia patients who lack suitable human leukocyte antigen-matched donors and fail immunosuppressive therapy.

The clinical impact of the ratio of C-reactive protein to albumin (CAR) in patients with acute- and lymphoma-type adult T-cell leukemia-lymphoma (ATL).

Recently, the ratio of C-reactive protein to albumin (CAR) is used as an inflammatory marker that has been demonstrated to be a simple and reliable prognostic factor in solid tumors and hematological malignancy. However, no studies of the CAR have been performed in patients with adult T-cell leukemia-lymphoma (ATL). We retrospectively analyzed the clinical features and outcomes in 68 newly diagnosed acute- and lymphoma-type ATL [(acute-(n=42) or lymphoma-type (n=26)] patients in Miyazaki Prefecture from 2013 to 2017. Furthermore, we investigated correlations between pretreatment CAR levels and clinical features. The median age was 67 years (range, 44 - 87). Patients were initially treated by either palliative therapy (n=14) or chemotherapy [n=54; CHOP therapy (n=37)/ VCAP-AMP-VECP therapy (n=17)], and showed median survival durations of 0.5 months and 7.4 months, respectively. The factors affecting OS by multivariate analysis were age, BUN, and CAR. Importantly, we revealed that the high CAR group (optimal cut-off point; 0.553) was a significant indicator of worse OS by multivariate analysis (p< 0.001, HR; 5.46). The median survival of patients with a CAR< 0.553 was 8.37 months, while patients with a CAR>0.553 had a median survival of 3.94 months. The different clinical features between high CAR and low CAR groups were hypoproteinemia and the implementation of chemotherapy. Furthermore, in the chemotherapy group, but not the palliative therapy group, CAR was a significant prognostic marker. Our study indicated that CAR may be a new simple and significant independent prognostic marker in acute- and lymphoma-type ATL patients.

Clinical and microbiological characteristics of bacterial meningitis in umbilical cord blood transplantation recipients.

Bacterial meningitis is a rare but severe infectious complication after hematopoietic stem cell transplantation. However, its clinical features were previously not clear. We reviewed the cases of 7 patients diagnosed with bacterial meningitis with a positive cerebrospinal fluid culture among 1147 patients who underwent cord blood transplantation (CBT) at our institution between September 2007 and September 2020. The diagnosis was made on day + 5- + 45, and 5 patients developed bacterial meningitis before neutrophil engraftment. The causative organisms were all Gram-positive cocci: Enterococcus faecium and Enterococcus gallinarum (2 patients each), and Staphylococcus haemolyticus, Streptococcus mitis/oralis, and Rothia mucilaginosa (1 patient each). Six patients developed bacterial meningitis secondary to prior or concomitant bacteremia caused by the same bacterium. Five patients had received anti-MRSA agents at onset: vancomycin in 3, teicoplanin in 1, and daptomycin in 1. After diagnosis of bacterial meningitis, linezolid was eventually used for 6 patients. Two patients with E. gallinarum were alive at day + 1380 and + 157 after CBT, respectively, whereas 5 patients died 17-53 (median 43) days after the onset of bacterial meningitis. Breakthrough meningitis in CBT can occur even during the use of anti-MRSA drugs, and intensive antibiotic treatment is necessary.