Appropriate referral timing to specialized palliative care service: survey of bereaved families of cancer patients who died in palliative care units.

Few studies have investigated appropriate referral timing of specialized palliative care (SPC) from the perspective of cancer patients' and families' experiences. We aimed to clarify appropriate SPC referral timing for patients with advanced cancer and their families. We used data from a nationwide bereaved family survey in Japan. We sent a questionnaire to 999 bereaved families of cancer patients who died in 164 palliative care units (PCUs) and analyzed the first SPC referral timing and how patients evaluated it. We defined SPC as outpatient or inpatient palliative care service comprising certified palliative care physicians, advanced-practice nurses, and multidisciplinary practitioners. Finally, 51.6% (n = 515) of all responses were analyzed. The SPC referral timing was evaluated as appropriate (26.1%), late or too late (20.2%), early or too early (1.2%), or none of these (52.5%). Of these, 32.3% reported that they were referred to an SPC when diagnosed with advanced or incurable cancer or during anti-cancer treatment, and 62.6% reported they were referred after anti-cancer treatment. Patient-perceived appropriateness of SPC referral timing was associated with their good death process. After excluding "none of these" responses, a significantly higher proportion of respondents who reported being referred to SPC at diagnosis and during anti-cancer treatment evaluated the response timing as appropriate, compared to those who reported being referred after anti-cancer treatment. Appropriate timing for SPC referrals relates to quality of death; findings suggest that appropriate timing is at the time of diagnosis or during anti-cancer treatment.

Prognostic model for patients with advanced cancer using a combination of routine blood test values.

PURPOSE: The purpose of this study was to develop a simple prognostic model based on objective indicators alone, i.e., routine blood test data, without using any subjective variables such as patient's symptoms and physician's prediction. METHODS: The subjects of this retrospective study were patients at the palliative care unit of Tohoku University Hospital, Japan. Eligible patients were over 20 years old and had advanced cancer (n = 225). The model for predicting survival was developed based on Cox proportional hazards regression models for univariable and multivariable analyses of 20 items selected from routine blood test data. All the analyses were performed according to the TRIPOD statement ( https://www.tripod-statement.org/ ). RESULTS: The univariable and multivariable regression analyses identified total bilirubin, creatinine, urea/creatinine ratio, aspartate aminotransferase, albumin, total leukocyte count, differential lymphocyte count, and platelet/lymphocyte ratio as significant risk factors for mortality. Based on the hazard ratios, the area under the curve for the new risk model was 0.87 for accuracy, 0.83 for sensitivity, and 0.74 for specificity. Diagnostic accuracy was higher than provided by the Palliative Prognostic Score and the Palliative Prognostic Index. The Kaplan-Meier analysis demonstrated a survival significance of classifying patients according to their score into low-, medium-, and high-mortality risk groups having median survival times of 67 days, 34 days, and 11 days, respectively (p < 0.001). CONCLUSIONS: We developed a simple and accurate prognostic model for predicting the survival of patients with advanced cancer based on routine blood test values alone that may be useful for appropriate advanced care planning in a palliative care setting.

Clinicopathological features of malignant lymphoma in Japan: the Miyagi Study.

The Miyagi Study is an epidemiological study of malignant lymphoma, including immunological and genetic analyses, constructed by a population-based registration system covering Miyagi prefecture, Japan. A total of 1,552 newly diagnosed cases in Miyagi between 2002 and 2008 were enrolled in this study; 75% were B-cell lymphomas, 19% were T-cell and natural killer-cell (T/NK-cell) lymphomas, and 5% were Hodgkin's lymphomas. The most frequent subtype of B-cell lymphoma is diffuse large B-cell lymphoma, followed by follicular lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (51%, 24% and 8%, respectively). Thus, follicular lymphoma accounts for 18.2% of newly diagnosed cases in Miyagi; unexpectedly, its frequency is similar to that reported in Western countries. The common subtypes of T/NK-cell lymphoma are peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma, and adult T-cell leukemia/lymphoma (30%, 15% and 14%, respectively). Most of the data are similar to those reported in Asian countries, except for follicular lymphoma. We also analyzed the CD20 expression in B-cell lymphomas by flow cytometry for the cell membrane expression and by immunohistochemistry for the cytoplasmic expression. The cell membrane expression of CD20 protein may determine the susceptibility of B-cell lymphomas to anti-CD20 antibody therapy. The lack of CD20 expression was confirmed by both methods in 4 cases of 585 newly diagnosed cases (0.7%) and in 5 of 67 recurrent cases (7.5%). Furthermore, 23 cases (6.5%) showed the discrepancy of CD20 expression between both methods. The Miyagi Study has revealed the latest epidemiological features of malignant lymphoma in Japan.

Favorable outcome of unrelated cord blood transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) is one of the highest-risk ALL groups. Whenever possible, patients with Ph(+)ALL should undergo allogeneic hematopoietic stem cell transplantation (HSCT) after induction of remission. Although unrelated cord blood transplantation (CBT) has become a common treatment in adult patients who lack a sibling donor, data on the efficacy of CBT for Ph(+)ALL are limited. We analyzed the clinical outcomes of 20 Ph(+)ALL patients who underwent CBT (n = 8) or unrelated bone marrow transplantation (BMT) (n = 12). The median age was 41 years (range, 17-55 years). All but one of the patients were treated with an imatinib-based regimen before HSCT, and 19 patients were in first complete remission (CR) and 1 patient was in second CR at the time of HSCT. Seventeen patients received a myeloablative conditioning regimen containing 12 Gy of total-body irradiation, and 3 received a reduced-intensity conditioning regimen. After a median of 26 months of follow-up, estimated 3-year overall and leukemia-free survival rates were 100% and 85%, respectively, after CBT, and 49% and 38%, respectively, after unrelated BMT. The CBT group had significantly better overall survival than the BMT group (P = .02). Although BCR-ABL transcript was detected in 4 of 8 CBT patients at transplantation, 7 patients remained in molecular CR. Our findings suggest that CBT may be a viable option as postinduction therapy for Ph(+)ALL in patients lacking a sibling donor.

Successful allogeneic hematopoietic stem cell transplantation for aggressive NK cell leukemia.

Aggressive natural killer cell leukemia (ANKL) is a highly aggressive lymphoproliferative disease. An appropriate therapeutic strategy for ANKL remains to be established, but a few case reports have suggested that allogeneic hematopoietic stem cell transplantation (allo-HCT) can be curative. Here, we report a young woman with ANKL showing central nervous system (CNS) invasion, who has been in complete remission for more than a year after allo-HCT following two courses of intravenous chemotherapy and several rounds of intrathecal chemotherapy. Intensive remission induction chemotherapy followed by conventional myeloablative allo-HCT is a promising approach for long-term remission in cases of this aggressive malignancy.

Allogeneic hematopoietic stem cell transplant following chemotherapy containing l-asparaginase as a promising treatment for patients with relapsed or refractory extranodal natural killer/T cell lymphoma, nasal type.

The prognosis of advanced extranodal NK/T cell lymphoma (ENKTL) is poor. Allogeneic hematopoietic stem cell transplant (allo-HSCT) has been suggested to be a promising treatment for this disease, but its utility has yet to be established. Here we retrospectively analyzed five cases of ENKTL treated with allo-HSCT in our institute. After induction chemotherapy, disease status at allo-HSCT was second CR in three patients and refractory in two patients. All patients received a myeloablative conditioning regimen, and GVHD prophylaxis consisted of tacrolimus or cyclosporine with short-term methotrexate. Only one patient who received conventional induction chemotherapy developed severe complications, which needed long-term treatment, while others who received chemotherapy containing l-asparaginase did not have severe complications. There were no cases of treatment-related mortality, and all patients survived without disease for a median follow-up period of 1911 days. These results suggested that allo-HSCT following l-asparaginase-containing induction chemotherapy might improve the outcome of advanced ENKTL.

[Severe autoimmune hemolytic anemia after ABO match living donor liver transplantation].

A case of severe autoimmune hemolytic anemia after ABO matched living donor liver transplantation. We present here a case of severe autoimmune hemolytic anemia after ABO matched living donor liver transplantation. The patient is 56 y.o male. He received living donor liver transplantation from his ABO matched son in May 2007. In July, he was suffered from a progressive anemia, and diagnosed as autoimmune hemolytic anemia by the laboratory examinations. Intensive treatment including predonisolone, azathiopurine, rituximab, plasma exchange, was given, however, the disease was resistant to the treatment. By the administration of cyclophosphamide combined with rituximab, remission was finally achieved. To date, immune mediated hemolytic anemia after ABO matched living donor liver transplantation has not been reported, although several cases of ABO mismatched living donor liver transplantation have been reported. His severe but transient clinical course of anemia suggests that the transient emergence of donor lymphocytes may be responsible for onset of hemolytic anemia.

Peripheral T cell lymphoma with a high titer of proteinase-3-antineutrophil cytoplasmic antibodies that resembled Wegener's granulomatosis.

Here, we present a 54-year-old man with proptosis and swelling below the left eyelid. Laboratory findings showed high levels of PR3-ANCA and histological examination of the first biopsy revealed acute inflammation. Together with the findings of MRI, a diagnosis of WG was made. However, the disease progressed rapidly and histological examination of the second biopsy revealed infiltration of neoplastic T lymphocytes with aberrant loss of CD7. A final diagnosis of peripheral T cell lymphoma, not otherwise specified (WHO) was made, and complete remission was achieved by chemotherapy. This is a very rare case of T cell lymphoma with a high titer of PR3-ANCA.

Plasma cell leukemia maintaining complete remission by syngeneic stem cell transplantation combined with low-dose thalidomide maintenance therapy.

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma, which is very aggressive and resistant to chemotherapy. We report a case of PCL successfully treated with syngeneic peripheral blood stem cell transplantation followed by low-dose thalidomide. As of March 2009, the patient has maintained CR for 39 months posttransplant. The clinical course of the present case suggests that autologous stem cell transplantation using a graft with reduced contamination of malignant cells followed by low-dose thalidomide maintenance therapy may improve the PCL treatment outcome.

Acquired hemophilia A with sigmoid colon cancer: successful treatment with rituximab followed by sigmoidectomy.

Acquired hemophilia A is a rare and potentially fatal condition of coagulopathy caused by autoantibodies against clotting factor VIII (factor VIII inhibitor). We report a case of a 63-year-old woman, who presented with a sudden onset of severe hemorrhagic tendency with exclusively prolonged activated partial thromboplastin time (APTT). She was diagnosed with acquired hemophilia A due to a decrease in factor VIII activity and a high titer of factor VIII inhibitor. Hemorrhage was well controlled by recombinant activated factor VII. Although the level of factor VIII inhibitor did not decline with prednisolone and cyclophosphamide, it became undetectable with rituximab. In parallel with controlling hemorrhage, malignancy, which may cause acquired hemophilia A, was searched for and sigmoid colon cancer was found. After the eradication of factor VIII inhibitor, surgical resection was performed uneventfully. Thereafter, acquired hemophilia A has been in complete remission without any additional therapy. The present case suggests the efficacy of rituximab for refractory acquired hemophilia A and the importance of the identification of underlying diseases that can cause acquired hemophilia A.

Interlaboratory comparison of quantitative RT-PCR based detection for minimal residual disease in leukemias: a standardization approach in Japan.

Real-time quantitative polymerase chain reaction (RQ-PCR) has been accepted as integral part of the management of patients with hematologic malignancies. Whereas standardization efforts of RQ-PCR, initiated by Europe Against Cancer (EAC) group, have been gradually widespread in the world, Japanese laboratories use their individual protocol for RQ-PCR analysis. Therefore, we assessed the variability of quantitative results obtained from 4 different laboratories in Japan, including 3 companies and Tohoku University Hospital, using identical peripheral blood or bone marrow samples of patients in chronic myeloid leukemia (CML; n = 11) and acute myeloid leukemia (AML; n = 2). RQ-PCR was designed to quantify the copy numbers of disease-specific fusion chimeras; BCR-ABL (CML) and AML1-ETO (AML). In 5 out of 13 samples, the quantitative results from 4 laboratories varied more than 10 times (up to 712 times). Thus, we next sought to determine factors affecting the variability of RQ-PCR results across laboratories, by sending back RNA and cDNA samples from each company to Tohoku University, and they were further proceed to yield quantitative data. The main difference between companies and Tohoku University was probably due to the difference of blood separation method (Blood lysis or Ficoll-Hypaque). On the other hand, the variability among 4 laboratories was the most noticeable in the PCR step, mainly attributable to the difference of primer/probe sequence among laboratories. In conclusion, our analyses indicate the importance to limit both preanalytical (sample processing) and analytical (RQ-PCR) interlaboratory variability for RQ-PCR protocol, and the need of further efforts on standardization program in Japan.

Aggressive B-cell lymphoma with dual surface immunoglobulin light-chain expression.

Dual surface immunoglobulin light-chain expression in B-cell malignant neoplasm is a rare event, and has been predominantly reported in chronic lymphocytic leukemia. Herein, we report a case of aggressive B-cell lymphoma with kappa/lambda-dual surface immunoglobulin light-chain expression of a 69-year-old woman. The lymphoma cells were positive for CD5, CD19, CD20, HLA-DR, Ig kappa and Ig lambda. Southern blot analysis confirmed rearranged bands for both light chains with a monoclonal heavy chain rearrangement. She was treated with a combination of rituximab and CHOP regimen, but died of the progressive disease. To our knowledge, this is the first case of aggressive B-cell lymphoma showing dual kappa/lambda expression; the possible mechanisms of abnormal light chain expression are discussed.