Home transfusions are implemented using diverse approaches in Japan.

BACKGROUND AND OBJECTIVES: Japan's ageing society has increased the need for home healthcare, including home transfusions. We hence aimed to elucidate the purpose and utilization of home transfusions in Japan, which has not been clarified to date. MATERIALS AND METHODS: Clinics throughout Japan that provide home care and have experience in performing blood transfusions were surveyed. The study period was February to December 2019, and information of patients receiving home red blood cell transfusions, including patient background, pre-transfusion laboratory data and the purpose of the transfusions, was collected. RESULTS: Haematological malignancies and solid tumours accounted for 70% of the patients' underlying diseases, with the former being significantly more common in urban areas. Regarding the purpose of the home transfusions, haematologists focused on symptom improvement, whereas gastroenterology surgeons focused on life support. Furthermore, maintenance of life was more likely to be the aim in the group of patients with the lowest level of activities of daily living. The main items that were significantly associated with a low haemoglobin level before transfusion included age ≥90 years and a gastroenterologist being the physician in charge. CONCLUSION: Home transfusions were found to be performed in a restrictive and diverse manner in Japan. Life support is the second most common purpose of home transfusion in Japan, and optimizing effective home transfusion remains a challenge.

Management system of home transfusion in Japan: A nationwide survey in 2019.

BACKGROUND AND OBJECTIVES: In Japan, there are various opinions on the pros and cons of home transfusion because of safety concerns. We hence aimed to elucidate the safety and availability of home transfusion in Japan, which has not been clarified to date. MATERIALS AND METHODS: Clinics throughout Japan that provide home care and have experience in performing blood transfusions were surveyed. The analysis period was February to December 2019. Basic information about the clinics, their collaboration system with core hospitals, storage method of red blood cells (RBCs) and the system for the management of patient information regarding transfusion reactions were investigated. RESULTS: Detailed information was obtained regarding the implementation of home transfusions by 51 clinics. The proportion of home care clinics performing home transfusions was 17.6%, and they were more frequently performed in urban regions. Approximately half of the clinics collaborated with a core hospital for emergency responses to transfusion reactions. At 84% of the clinics, RBC units were stored in refrigerators that were not exclusively allocated to blood storage. Nurses and family members were involved as patient attendants in 83% and 77% of the home transfusions, respectively. No serious transfusion reactions were reported among the 150 patients in 2019, nor the 623 patients up to 2018. CONCLUSION: From data on its availability and safety, home transfusions are considered to be in the developing phase in Japan. Increased cooperation between hospitals and clinics is crucial towards improving the home transfusion system in Japan in the future.

False-positive blood culture results in patients with hematologic malignancies.

Blood cultures are the most valuable tool when bacteremia is clinically suspected. Technical advances have led to the development of automated blood culture systems to detect bacterial infections. Usually positive signals in automated blood culture systems result from the proliferation of microorganisms. Cases are classified as false-positive when the automated blood culture system produces a positive signal but no microorganisms are detected on Gram-stained smears and no microorganism growth is observed in blood subcultures. False-positive blood culture results are very rare in patients with hematologic malignancies. Recently, we encountered four patients who had false-positive blood culture results. Two of the patients were diagnosed with acute leukemia, involving hyperleukocytosis and an excess of blasts. The other two patients were diagnosed with acute leukemia and diffuse large B cell lymphoma with leukocytopenia. Although hypercapnia or acidosis, apart from hyperleukocytosis, might also cause false-positive results, our cases clearly did not have these conditions. We should be aware of the possibility that false-positive blood culture results can occur in patients with leukocytopenia, as well as hyperleukocytosis. To understand the mechanisms responsible for the observed false-positive results, additional studies are needed after the accumulation of similar cases.

Geriatric screening tools predict survival outcomes in older patients with diffuse large B cell lymphoma.

The proportion of elderly patients with diffuse large B cell lymphoma (DLBCL) appears to be increasing, with outcomes varying widely because of the patients' heterogeneity. Geriatric assessment is used to predict prognosis in elderly patients with DLBCL, but the utility of two simple screening tools for patients with DLBCL, the Flemish version of the Triage Risk Screening Tool (fTRST) and G8, has remained to be elucidated. We retrospectively assessed patients using fTRST and G8, and evaluated the impacts of the scores on survival outcomes in older patients with newly diagnosed DLBCL. A total of 59 patients aged 65 years or older and who were diagnosed with DLBCL were included. The median age was 77 years (range, 65-91 years), and the initial treatments were R-CHOP (63%) and R-THPCOP (31%). The estimated 2-year overall survival (OS) rate was significantly lower in patients with abnormal fTRST scores (≥ 2; N = 17) than in those with normal fTRST scores (< 2; N = 42): (50.5% (95% CI, 22.7-73.0%) vs. 82.2% (95% CI, 63.8-91.8%), P = 0.007). The estimated 2-year OS rate was significantly lower also in patients with abnormal G8 scores (≤ 14; N = 38) than in those with normal G8 scores (> 14; N = 21): (66.1% (95% CI, 46.7-79.5%) vs. 86.8% (95% CI, 55.7-96.7%), P = 0.03, respectively). These associations were independently significant after adjusting for other significant factors by multivariate analysis. These results suggest that the easy-to-use geriatric screening tools, fTRST and G8, have strong prognostic value for OS in older patients with DLBCL.

Diagnostic performance of procalcitonin, presepsin, and C-reactive protein in patients with hematological malignancies.

INTRODUCTION: Infections represent a major complication of hematological malignancies. C-reactive protein (CRP) and procalcitonin (PCT) have been used as diagnostic biomarkers of infections, but do not produce definitive findings. Recently, a new biomarker, presepsin, has been used as a diagnostic tool for detecting infections in the fields of emergency and neonatal medicine. However, the usefulness of presepsin for identifying infections in patients with hematological malignancies, including those who develop febrile neutropenia, remains unclear. METHODS: In this study, we retrospectively analyzed the utility of PCT, presepsin, and CRP as biomarkers of infections during 49 febrile episodes that occurred in 28 patients with hematological malignancies. RESULTS: The levels of PCT, but not those of CRP or presepsin, were significantly higher in the infection group than in the uninfected group (P<.03), indicating that PCT might be a more sensitive biomarker of infections. No differences in presepsin levels were detected between the patients with and without neutropenia, or between the infected and uninfected patients with neutropenia, indicating that presepsin might have less diagnostic value in patients with neutropenia. CONCLUSIONS: We conclude that PCT might provide additional information and could be used in combination with other biomarkers to detect infections in patients with hematological malignancies.

A phase II study of bendamustine plus rituximab in Japanese patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma previously treated with rituximab: BRB study.

To evaluate the efficacy and safety of a combined regimen of bendamustine (B) and rituximab (R) in Japanese patients with relapsed/refractory (r/r) indolent B-cell non-Hodgkin lymphomas (B-NHLs) and mantle cell lymphoma (MCL). Patients aged 20-79 years with pathologically confirmed B-NHLs or MCL, which were r/r after 1-2 R-containing regimens, were included in this study. The BR regimen consisted of B (90 mg/m(2)) for two consecutive days and R (375 mg/m(2)) on day 1, 2, or 3. The course was repeated every 4 weeks for up to four cycles. Fifty-three patients were enrolled in this study and analyzed. The diagnosis included follicular lymphoma (FL) (77 %), mucosa-associated lymphoid tissue lymphoma (13 %) and others (10 %). Forty-seven (90 %) patients completed four cycles of treatment as per schedule. Best overall response rate (ORR) and complete response rate (CRR) was 94 and 71 %, respectively (for FL, ORR 95 % and CRR 80 %). The treatment was well tolerated and the primary toxicity was myelosuppression; the incidence of grade 3/4 leukopenia and neutropenia were 42 and 40 %, respectively. There were no grade 5 toxicities. The BR regimen is safe in Japanese patients with r/r indolent B-NHLs and MCL, and is effective for those with r/r indolent B-NHLs. For the evaluation of late toxicity, especially infection, longer follow-up of this cohort is needed.

Erythroid crisis caused by parvovirus B19 transmitted via red blood cell transfusion.

A 41-year-old man with hairy cell leukemia developed erythroid crisis after the transfusion of red cell concentrate. He was diagnosed with Parvovirus B19 infection based upon the presence of B19-specific IgM antibody and viral DNA in the sera. The repository sample from the corresponding red cell concentrate was negative for B19 antigen by red cell hemo-agglutination method, but was found to contain B19 virus DNA. Furthermore, a genomic PCR direct sequencing showed that B19 in both patient's sera and repository sample were identical. This is the first report directly demonstrating the transmission of B19 through B19 antigen-negative red cell concentrate transfusion. Further accumulation of the cases is warranted to estimate its incidence and to reconsider the screening methods of blood products.

Guidelines for safety management of granulocyte transfusion in Japan.

Granulocyte transfusion (GTX) has recently been revived by the ability to stimulate granulocyte donors with granulocyte colony-stimulating factor (G-CSF), resulting in a greatly increased number of cells that can be collected. However, there is a paucity of guidelines for assessing the appropriateness and safety management of GTX. The objective of this study was to establish guidelines for the safety management of GTX appropriate for the clinical situation in Japan. The Japan Society of Transfusion Medicine and Cell Therapy, Granulocyte Transfusion Task Force issued the first version of guidelines for GTX considering the safety management of both granulocyte donors and patients who receive GTX therapy. The current guidelines cover issues concerning: (1) the appropriateness of medical institutions, (2) management of granulocyte donors, (3) quality assurance of granulocyte concentrates, (4) administration of granulocyte concentrates, (5) evaluation of the effectiveness of GTX therapy, and (6) complications of GTX therapy. The simple 'bag separation method' without apheresis may be recommended for granulocyte collection in pediatric patients. The first version of guidelines for GTX therapy has been established, which may be appropriate for the clinical situation in Japan. Care should be taken to perform the safety management of both granulocyte donors and patients who receive GTX therapy.

Long-term clinical outcomes for patients with lower limb ischemia implanted with G-CSF-mobilized autologous peripheral blood mononuclear cells.

BACKGROUND: Many studies have described the clinical effects of treating critical limb ischemia with granulocyte colony-stimulating factor-mobilized autologous peripheral blood mononuclear cells (M-PBMNC); however, there are no long-term data available on survival, limb salvage, or prognostic factors. METHODS: To investigate the long-term clinical outcomes of M-PBMNC implantation, we reviewed data for 162 consecutive patients with limb ischemia who were treated with M-PBMNC implantation at 6 hospitals between 2001 and 2006. A subset of 123 patients with homogenous clinical profiles was selected for prognostic factor analysis. RESULTS: Of the 162 patients, 50 died during the follow-up period. The median follow-up time for surviving patients was 26.4 months. The 2-year survival rate was 65% for the 140 patients with arteriosclerosis obliterans (ASO), and 100% for the 11, 4 and 7 patients with thromboangiitis obliterans (TAO), diabetic gangrene (DG) and connective tissue disease (CTD), respectively. The 1-year amputation-free rates for ASO, TAO, DG and CTD were 70%, 79%, 75% and 83%, respectively. Common serious adverse events included heart failure (15 cases), myocardial infarction (15 cases), serious infection (13 cases), stroke (10 cases), and malignant tumor (9 cases). Significant negative prognostic factors associated with overall survival were ischemic heart disease and collection of a small number of CD34-positive cells. Factors associated with time-to-amputation and amputation-free survival were a combination of Fontaine classification and lower limb gangrene, and history of dialysis. CONCLUSIONS: Collection of a small number of CD34-positive cells and ischemic heart disease were associated with a reduction in overall survival.

[Sideroblastic anemia after prolonged linezolid therapy].

Linezolid is an effective and well-tolerated antibiotic for the treatment of infections caused by Gram-positive pathogens. Some reports have shown that linezolid treatment for more than 2 weeks has been associated with reversible bone marrow suppression, especially thrombocytopenia and anemia. We encountered a case of sideroblastic anemia following prolonged linezolid therapy in a laryngeal cancer patient. He received linezolid therapy for multiple abscesses due to MRSA. Before treatment, the Hb level was 12.5 g/dl and then slowly decreased to 5.9 g/dl for 2 months during treatment. Ringed sideroblasts were detected in the bone marrow. Linezolid was discontinued and the Hb level was slowly increased. This case was considered to reflect a rare complication of linezolid therapy.

[Examination and treatment for dilutional thrombocytopenia].

Massive transfusion is defined as transfusion of more than total blood volume within 24 hours. There are several adverse effects associated with massive transfusion, and dilutional thrombocytopenia is known as one of the major adverse effects. Dilutional thrombocytopenia is caused by platelet loss out of the body and platelet dilution with replaced red cells and crystalloids. Volume of blood loss or replaced volume is a good indicator of dilutional thrombocytopenia, and previous reports suggest that severe thrombocytopenia doesn't occur before replaced volume surpasses over one hundred and fifty percent of total blood volume. Recently, an automated blood cell counter has spread and platelet count is available in a short time, even at night. To treat the patient with dilutional thrombocytopenia, platelet count is very helpful to decide when to start platelet transfusion. When platelet count decreases as low as 50,000/mm3, platelet transfusion should be considered. Nowadays, dilutional thrombocytopenia is less frequent complications of massive transfusion than before, because platelet transfusion tends to be performed before platelet count fall to the critical point. Thus, exceeded platelet transfusion might become another problem after massive transfusion.

Long-term follow-up of allogeneic bone marrow transplantation after reduced-intensity conditioning in patients with chronic myelogenous leukemia in the chronic phase.

Although allogeneic transplantation is a curative therapy for chronic myelogenous leukemia (CML), treatment-related mortality is still a major cause of death after transplantation, especially in older patients. We investigated the safety and efficacy of reduced-intensity conditioning consisting of low-dose (600 cGy) total body irradiation and cytosine arabinoside (1 g/m2) together with a continuous infusion of granulocyte colony-stimulating factor and cyclophosphamide (120 mg/kg) in patients with CML in the chronic phase. Fractionated splenic irradiation (5 Gy) was also administered as part of the conditioning treatment. Eight patients older than 40 years underwent allogeneic bone marrow transplantation from an HLA-matched sibling following this conditioning. Regimen-related toxicities (equal to or greater than grade III) were not observed. Rapid restoration of 100% donor chimerism was confirmed by fluorescence in situ hybridization methods in 5 sex-mismatched transplant recipients. One patient died from severe acute graft-versus-host disease and another from Pneumocystis carinii pneumonia early in the course of transplantation. A sustained engraftment was achieved in 5 long-term survivors; in 1 case, the graft was rejected but the Philadelphia chromosome and BCR/ABL-negative autologous hemopoiesis were restored. After a minimum follow-up period of 60 months, 6 patients, including the patient with restored autologous hemopoiesis, were still alive and in remission with 100% donor chimerism. Six years after the transplantation, 1 patient experienced a cytogenetic relapse, which was successfully treated with donor lymphocyte infusions. In summary, this reduced-intensity conditioning resulted in a cure with markedly reduced regimen-related toxicities in this relatively older cohort of patients with CML.

Expression of lineage markers by CD34+ hematopoietic stem cells of adult mice.

OBJECTIVE: By using a murine transplantation model, we studied the relationship between CD34 expression and expression of CD4 and Mac-1 by hematopoietic stem cells of normal adult mice. MATERIALS AND METHODS: Cells from Ly-5.1 C57BL/6 mice were used as test cells and lethally irradiated Ly-5.2 mice were used as recipient mice. Peripheral blood was obtained 6 months posttransplantation to analyze engraftment of donor-derived cells. RESULTS: First, we determined that CD34- long-term reconstituting cells are CD4-, while some CD34+ stem cells express CD4. We then studied Mac-1 expression. Mac-1(-) and Mac-1(low) populations of both CD34- and CD34+ cells were capable of long-term reconstitution. Mac-1(high) population of CD34+ cells but not of CD34- cells also engrafted. CONCLUSIONS: These results strongly indicate that depletion of Mac-1(+) and CD4(+) cells in stem cell purification may inadvertently discard significant populations of CD34+ stem cells. Since positive selection based on CD34 expression is the current practice for purification of human stem cells, our studies may possess implications in the purification of human hematopoietic stem cells.