Cyrus C. Hsia

Red blood cell processing methods and in-hospital mortality: a transfusion registry cohort study

BACKGROUND Quality of red blood cells (RBCs) varies depending on the method of processing the whole blood donation, and the method of processing might affect outcomes in patients transfused RBCs. We aimed to establish whether an association exists between in-hospital mortality and RBC processing method and duration of storage. METHODS We did a retrospective registry cohort study using data from three acute care hospitals in Hamilton, ON, Canada, and Canadian Blood Services over a 6-year period (2008-14). Adult patients (≥18 years) who were admitted to hospital and who received RBC transfusions were included in the study. All transfused RBCs were characterised by the method of processing (red cell filtered or whole blood filtered) and storage age (fresh 1-7 days, mid 8-35 days, and old 36-42 days). The primary outcome was in-hospital mortality. We used Cox proportional hazards regression with time-dependent stratification variables and fixed stratification variables, and controlled for patient covariates. FINDINGS Between April 1, 2008, and March 31, 2014, 91 065 RBC transfusions were given to 23 634 adults who were included in the analyses. When storage duration was included in the model, in-hospital mortality was significantly increased with fresh whole blood filtered units compared with the reference group of mid-age red cell filtered units (hazard ratio 2·19, 95% CI 1·09-4·42; p=0·033). Differences between other age and processing categories were not significant. INTERPRETATION The potential effect of whole blood processing methods on patient outcomes is worthy of further investigation, since adverse outcomes could be reduced by minor changes to blood processing methods and inventory management policies. FUNDING Canadian Blood Services, Health Canada, and the Canadian Institutes of Health Research.

Incidence and natural history of intravenous immunoglobulin–induced aseptic meningitis: a retrospective review at a single tertiary care center

Aseptic meningitis is a rare but significant complication of intravenous immunoglobulin (IVIG) therapy. The majority of literature is limited to case reports, so the true incidence of this complication is uncertain.

Effect of a thrombopoietin receptor agonist on use of intravenous immune globulin in patients with immune thrombocytopenia

Thrombopoietin receptor agonists are new treatments for patients with chronic immune thrombocytopenia (ITP). How one of these agent, romiplostim, has impacted practice patterns, especially the use of intravenous immune globulin (IVIG), has not been evaluated outside of clinical trials.

Combined accurate platelet enumeration and reticulated platelet determination by flow cytometry

Diagnosing the cause of thrombocytopenia often requires a bone marrow aspiration or biopsy, an invasive procedure. Reticulated platelets (RP) are immature RNA containing platelets, accurate RP enumeration has yet to be achieved, partially due to the lack of a robust reference method.

Mediastinal Choriocarcinoma Masquerading as Relapsed Hodgkin Lymphoma

Primary mediastinal choriocarcinoma is a rare extragonadal germ cell malignancy. We describe the first case of a patient who developed mediastinal choriocarcinoma after treatment for Hodgkin lymphoma (HL). A 25-year-old man with classic HL, nodular sclerosis subtype, underwent treatment with splenectomy followed by radiation therapy. Unfortunately, his disease relapsed with a paraspinal mass, and he was subsequently treated with MOPP (mechlorethamine, Oncovin, procarbazine, and prednisone) alternating with ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). He achieved a complete remission after 6 cycles. Ten years after treatment, the patient presented with a persistent cough, haemoptysis, right supraclavicular lymphadenopathy, and weight loss. His chest X-ray showed opacification of the lower right hemithorax with a widened mediastinum. Given unresponsiveness to several antibiotics and lack of evidence for lung volume loss, there were concerns over lung infiltration with relapsed lymphoma. Transbronchial fine needle aspiration biopsy suggested recurrence of his HL. MOPP alternating with ABVD was again given. Due to disease progression, brachytherapy as well as a cocktail of dexamethasone, cytarabine, and cisplatin were also tried. However, on a subsequent excisional lymph node biopsy, it turned out that the tumour was in fact choriocarcinoma and not relapsed HL. Unfortunately, despite aggressive therapy, the patient’s disease rapidly progressed, and he died within 2 weeks.

Sweet's syndrome in chronic myelomonocytic leukemia

A 64-year-old male with a history of resected rectal cancer presented with a 1-week history of fever, chills, myalgias, generalized malaise, and 4-day history of a productive cough with yellow sputum and dyspnea. With the onset of his respiratory symptoms, he had an abrupt appearance of a skin rash on his hands and extremities. On examination, there were multiple violaceous pustular nodules on the dorsum of his hands (Image 1: Panel A) and extremities (Image 1: Panel B). Initial investigations revealed hemoglobin of 117 g/ L, platelet count of 401 3 10/L, an elevated leukocyte count of 68 3 10/L with absolute neutrophil count of 60.2 3 10/L, and monocyte count of 5.4 3 10/L. Blood cultures were negative. A chest radiograph showed extensive bilateral patchy airspace opacities compatible with pneumonia (Image 1: Panel C). Skin biopsy revealed neutrophilic dermatosis. No viral inclusions were seen and the Gram stain and fungus stain (GMS) did not demonstrate any organisms. An erythrocyte sedimentation rate (ESR) was elevated at 92 mm/h. His pneumonia was treated and his leukocyte count decreased to 20 3 10/L with persistent skin lesions and monocytosis at discharge 11 days later. A subsequent bone marrow aspirate supported an underlying diagnosis of chronic myelomonocytic leukemia (CMML, Panel D) and normal male karyotype. Two months later, his skin lesions still persisted and only improved with a course of high-dose oral prednisone. The lesions resolved within a few days of starting prednisone and his CMML was managed supportively. Sweet’s syndrome, also called acute febrile neutrophilic dermatosis, presents typically with an abrupt onset of rapidly growing erythematous, painful papules, nodules, or plaques over the head, neck, arms, and legs [1]. Additionally, vesicles or bullae may appear on top of these lesions [1]. Skin biopsy will show papillary and mid-dermal infiltration of neutrophils. This condition is associated with respiratory infections, malignancies, and certain medications. Acute myeloid leukemia has been commonly associated with this conditions but it has been reported with other myeloid malignancies such as myelodysplastic syndrome and CMML rarely [2]. In this patient, Sweet’s syndrome may be associated with his pneumonia but most likely was due to his underlying CMML as the association with respiratory infections occur mainly in children [3]. This case highlights the importance of searching for an underlying cause such as a hematologic malignancy even in the presence of an active infection.

Use of n-of-1 (single patient) trials to assess the effect of age of transfused blood on health-related quality of life in transfusion-dependent patients.

The impact of age of red blood cells on health‐related quality of life (HRQL) in patients who require chronic transfusions is not known. We assessed this using n‐of‐1 trials in patient populations where large randomized trials have not been done to date.

Leishmaniasis involving the bone marrow of a patient with multiple myeloma

Dear Editor, A 64-year-old man with multiple myeloma was treated with high-dose dexamethasone followed by autologous stem cell transplant and, subsequently, lenalidomide plus dexamethasone for relapsed disease with a very good partial response. After 2 years of therapy, he developed progressive pancytopenia with total white blood cell count 1.5×10/L, hemoglobin 93 g/L, platelet count 81×10/L, and neutrophil count 0.7×10/L. Despite holding lenalidomide and dexamethasone, there was no improvement in his pancytopenia. The serum protein electrophoresis showed a marked polyclonal gammopathy (total IgG 57.6 g/L), and a bone marrow aspirate showed a polyclonal plasma cell population representing about 10 % of the total nucleated cell count. Importantly, the aspirate showedmany intraand extracellular microorganisms (Fig. 1). CTscan of the abdomen showed hepatosplenomegaly without any focal definitive lesions. Further history revealed that he had spent a week in Texas on a farm that housed imported exotic animals (including zebras and deer from Africa and South America) several months prior to developing this pancytopenia. Extensive serological tests for infectious causes of his presentation including toxoplasmosis, histoplasmosis, coccidioidomycosis, Q fever, and cat scratch disease were negative. Fungal culture was done from the aspirate and was negative. Due to clinical concern about the possibility of visceral leishmaniasis, leishmaniasis serology was evaluated and found to be positive. Subsequent polymerase chain reaction (PCR) test confirmed the diagnosis of visceral leishmaniasis. Initial treatment with liposomal amphotericin was started, but due to an immediate rise in serum creatinine, this therapy was discontinued and the patient received miltefosine. Within 2 weeks, all blood counts were back to normal. Miltefosine was given for 28 days followed by secondary prophylaxis with amphotericin every 3 weeks for 9 months. Currently, the patient has been off all medications for 6 months without signs of leishmaniasis recurrence. His blood counts remain normal, his polyclonal gammopathy resolved, and his multiple myeloma remains in complete remission. Leishmaniasis is a vector-borne disease that is caused by an obligate intra-macrophage protozoa. It is endemic in large areas of the tropics, subtropics, and the Mediterranean basin. This disease is characterized by both diversity and

A Unique Hairy Cell Leukemia Variant.

A 65-year-old woman presented with easy bruising, left upper quadrant pain, decreased appetite, and weight loss. She had splenomegaly and lymphocytosis (lymphocyte count of 11.6 × 109/l), with remarkably abnormal appearing morphology. Her hemoglobin and platelet counts were normal. Peripheral blood flow cytometry revealed a monoclonal B-cell population expressing CD11c, CD25, CD19, CD20, and CD103. An initial diagnosis of hairy cell leukemia (HCL) was made, and the patient was treated with a standard 5-day course of cladribine. However, her lymphocytosis improved transiently, with a relapse 4 months later. There was no improvement in her splenomegaly. An HCL variant (HCL-v) was considered based on her resistance to treatment with a purine nucleoside analog. A subsequent splenectomy improved symptoms. Two years after, the patient suffered a relapse and underwent 6 cycles of CHOP-R (cyclophosphamide, hydroxydaunomycin, oncovin, prednisone, and rituximab), achieving partial remission. While under observation, she progressed with lymphocytosis 6 months later and was treated with pentostatin. There was no significant improvement in her disease, and she died 8 weeks following treatment initiation. HCL-v is a clinically more aggressive mature B-cell lymphoma than HCL with worse splenomegaly, higher lymphocyte counts, and resistance to typical HCL therapy with purine nucleoside analogs. Early recognition of HCL-v in the history, physical examination, and investigations with morphology and flow cytometry is key to patient management. Further, as in our case of HCL-v, cell morphology can be distinctly atypical, with large nucleoli and extremely convoluted nuclei. The distinction between HCL and HCL-v is important as HCL-v patients require more aggressive therapy and closer follow-up.

Response to "Need to minimize bias when surveying patient attitudes to stopping cml treatment".

The Editor, Current Oncology June 23, 2014 We thank Villemagne et al. for their comments, and we will address some of the issues that they raised. It is important that clinicians understand patient concerns and values before key treatment decisions are made. Hypothetical scenarios such as “what if” or “when this occurs” are discussed routinely in close patient–physician relationships, and for that reason, we reject the assertion that our sample is not representative of patients with chronic myeloid leukemia (cml) who might be eligible for stopping tyrosine kinase inhibitors (tkis). We contend that it is not necessary for patients to have achieved a sustained deep molecular response (Bcr-Abl ≤ 0.0032%) to make informed responses to a hypothetical scenario. It is unknown whether a group of patients who have achieved a deep molecular response would respond differently than would patients whose molecular response might have not been optimal. For the second point, consecutive patients with cml being treated by the investigators were approached for participation in the study during the study period. We agree with the third comment that our single-centre study might have allowed for the opinion or influence of a small number of clinicians to have a significant impact on patient responses, which is explicitly stated in the Discussion section of the article. The reference cited by Villemagne et al. to support the statement that “studies of compliance in cml have shown a much more complex array of behaviours and choices” is also a single-centre study and subject to the same limitations1. In response to the measurement tool, Villemagne et al. suggest that the first two measures of patient preference for relapse rates are confounded with willingness to stop treatment. Again, it is important to understand that the patient scenario is laid out with the remarks that the questions are hypothetical, that the response will not affect current clinical care, and that the very first question is asking about willingness to stop. There is no assumption of willingness to stop in the first question. It was not our intention to use only patients who are in deep molecular response and who are willing to stop to assess risk acceptability. Rather, we wanted to gauge the response of the general cml population who might or might not be faced with that decision. The visual analog scales were not modified from their original formats (with a 0 labelled the worst imaginable health state and a “sad face”). That presentation did cause some difficulty in interpretation of the question by the patients, but it was clarified by the interviewer in a standardized fashion. We agree that patient compliance is complex, that our choices do not make a distinction between unintentional and deliberate noncompliance, and that self-reported measures of compliance are notoriously unreliable. The two references listed by Villemagne et al. as having validated measures for patient-reported outcomes of compliance and toxicity specific to cml have no documentation of the inclusion of cml patients in the studies2,3. The first study, by Morisky et al.2, dealt with adherence in hypertensive patients, and the second study, by Cleeland et al.3, categorized only 7 of 527 patients as having chronic leukemia in the outpatient setting, without clarifying the type of chronic leukemia. We agree that the evidence suggests that patients are more likely to misrepresent their treatment adherence in clinical settings; however, we conducted an interviewer-led study using an independent surveyor who had no involvement in patient care to minimize such bias. As discussed, conveying risk in treatment decisions is complex and is influenced by patient–physician communication and relationship4. Those interactions are also affected by physician beliefs about the quality of evidence, which influences how information about risk is conveyed to patients. Objective standardized patient education and decision tools can be useful adjuncts in such circumstances5. We have outlined the various limitations of our study, but it nevertheless represents real-life discussions that can arise with patients who are generally well informed and interested in taking greater ownership of their health. Larger studies of stopping tkis are being done, and we anticipate that the question of stopping will arise for some patients. Our study offers a glimpse of how patients might approach this issue. Thus, the average patient with cml on a tki approaching this hypothetical question based on a personal opinion of “compliance” and a personal view of side effects might or might not be willing to stop. Larger multicentre studies can be performed, but ultimately each patient makes a personal decision based on their own perceptions of level of “compliance,” severity of side effects, and risk acceptability. The main message of the paper is that patients are capable of balancing risk, and the choice to stop a tki should involve shared decision-making between the patient and the clinician, which has been reported to be the approach preferred by most patients with cancer6.