Efficacy and safety of heterologous booster vaccination with Ad26.COV2.S after BNT162b2 mRNA COVID-19 vaccine in haemato-oncological patients with no antibody response.

Patients with haemato-oncological malignancies are one of the high-risk groups for a severe course in case of COVID-19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato-oncological patients without antibody response after double-dose BNT162b2 messenger (m-)RNA COVID-19 vaccine. A total of 32 haemato-oncological non-responders to double-dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double-dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato-oncological patients.

CANOMAD: a neurological monoclonal gammopathy of clinical significance that benefits from B-cell-targeted therapies.

CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M [IgM] paraprotein, cold agglutinins, and disialosyl antibodies) is a rare syndrome characterized by chronic neuropathy with sensory ataxia, ocular, and/or bulbar motor weakness in the presence of a monoclonal IgM reacting against gangliosides containing disialosyl epitopes. Data regarding associated hematologic malignancies and effective therapies in CANOMAD are scarce. We conducted a French multicenter retrospective study that included 45 patients with serum IgM antibodies reacting against disialosyl epitopes in the context of evocating neurologic symptoms. The main clinical features were sensitive symptoms (ataxia, paresthesia, hypoesthesia; n = 45, 100%), motor weakness (n = 18, 40%), ophthalmoplegia (n = 20, 45%), and bulbar symptoms (n = 6, 13%). Forty-five percent of the cohort had moderate to severe disability (modified Rankin score, 3-5). Cold agglutinins were identified in 15 (34%) patients. Electrophysiologic studies showed a demyelinating or axonal pattern in, respectively, 60% and 27% of cases. All patients had serum monoclonal IgM gammopathy (median, 2.6 g/L; range, 0.1-40 g/L). Overt hematologic malignancies were diagnosed in 16 patients (36%), with the most frequent being Waldenström macroglobulinemia (n = 9, 20%). Forty-one patients (91%) required treatment of CANOMAD. Intravenous immunoglobulins (IVIg) and rituximab-based regimens were the most effective therapies with, respectively, 53% and 52% of partial or better clinical responses. Corticosteroids and immunosuppressive drugs were largely ineffective. Although more studies are warranted to better define the optimal therapeutic sequence, IVIg should be proposed as the standard of care for first-line treatment and rituximab-based regimens for second-line treatment. These compiled data argue for CANOMAD to be included in neurologic monoclonal gammopathy of clinical significance.

Pedigree investigation, clinical characteristics, and prognosis analysis of haematological disease patients with germline TET2 mutation.

BACKGROUND: Increasing germline gene mutations have been discovered in haematological malignancies with the development of next-generation sequencing (NGS), which is critical for proper clinical management and long-term follow-up of affected individuals. Tet methylcytosine dioxygenase 2 (TET2) is one of the most common mutations in haematological neoplasms. We aimed to compare the clinical characteristics of patients with germline and somatic TET2 mutations in haematological diseases and to analyse whether germline TET2 mutations have a family aggregation and tumour predisposition. METHODS: Out of 612 patients who underwent NGS of 34 recurrently mutated genes in haematological diseases, 100 haematological patients with TET2 mutations were selected for further study. Somatic mutations were detected by NGS in bone marrow/peripheral blood genomic DNA (gDNA). Germline TET2 mutations were validated in nail/hair gDNA by Sanger sequencing. Digital data were extracted from the haematology department of the West China Hospital of Sichuan University. TET2 mutation results were analysed by referencing online public databases (COSMIC and ClinVar). RESULTS: One hundred patients were studied, including 33 patients with germline and 67 patients with somatic TET2 mutations. For germline TET2 mutations, the variant allele frequency (VAF) was more stable (50.58% [40.5-55], P < 0.0001), and mutation sites recurrently occurred in three sites, unlike somatic TET2 mutations. Patients with germline TET2 mutations were younger (median age 48, 16-82 years) (P = 0.0058) and mainly suffered from myelodysplastic syndromes (MDS) (n = 13, 39.4%), while patients with somatic TET2 mutations were mainly affected by acute myeloid leukemia (AML) (n = 26, 38.8%) (P = 0.0004). Germline TET2 mutation affected the distribution of cell counts in the peripheral blood and bone marrow (P < 0.05); it was a poor prognostic factor for MDS patients via univariate analysis (HR = 5.3, 95% CI: 0.89-32.2, P = 0.0209) but not in multivariate analysis using the Cox regression model (P = 0.062). CONCLUSIONS: Germline TET2 mutation might have a family aggregation, and TET2 may be a predisposition gene for haematological malignancy under the other gene mutations as the second hit. Germline TET2 mutation may play a role in the proportion of blood and bone marrow cells and, most importantly, may be an adverse factor for MDS patients.

Clonal Megakaryocyte Dysplasia with Normal Blood Values Is a Distinct Myeloproliferative Neoplasm.

INTRODUCTION: In 1991, we reported 18 persons with a clinical-pathologic entity and termed atypical myeloproliferative disorder because they did not meet the contemporary diagnostic criteria for a myeloproliferative neoplasm. We sought to gain further knowledge on this disease entity. METHODS: This retrospective cohort study included consecutive subjects registered in the database of the Center for the Study of Myelofibrosis in Pavia, Italy, from 1998 to 2020 (June), and diagnosed with atypical myeloproliferative disorder according to our adjudicated criteria. We studied clinical, histological, cytogenetic, and molecular covariates and risks of thrombosis, disease progression, and death. Data were compared with those of concurrent subjects with prefibrotic myelofibrosis. RESULTS: Fifteen new subjects with atypical myeloproliferative disorder were identified. Seven were male. Median age was 50 years (IQR, 41-54 years). Thirteen were diagnosed with a synchronous symptomatic or incidentally detected thrombotic event. The bone marrow showed megakaryocyte hyperplasia with dysplasia. JAK2V617F was present in 10 subjects and CALR mutation in one. No other somatic mutations were identified in next generation sequencing. After a median follow-up of 101 months (IQR, 40-160 months), no subject had disease progression or blast transformation. Incidence of post-diagnosis or recurrent thrombosis was 3.9 events (95% confidence interval, 3.5-4.0) and 5.0 events (4.6-5.6) per 100 person-years. Features of subjects with atypical myeloproliferative disorder differed markedly from those of 546 subjects with prefibrotic myelofibrosis. CONCLUSION: Our data indicate that these 15 persons have a distinct myeloproliferative neoplasm. We propose naming this new disorder clonal megakaryocyte dysplasia with normal blood values.

The Status of Pediatric Patients With Hematologic Malignancy During COVID-19 Pandemic in Wuhan City, China.

Data regarding the epidemiologic characteristics and clinical features of pediatric hematologic patients are limited in this corona virus disease 2019 (COVID-19) crisis. We investigated the status of 113 pediatric hematologic patients in Wuhan union hospital during the COVID-19 pandemic from January 23 to March 10, 2020. All the patients had routine blood and biochemical examination, as well as chest computed tomography scans, and the nucleic acid, immunoglobulin G-immunoglobulin M combined antibodies tests for SARS-CoV-2. After admission, all patients were single-room isolated for 5 to 7 days. The results showed that only 1 (0.88%) child with leukemia was confirmed to have SARS-CoV-2 infection and 15 (13.2%) children were considered as suspected cases. Comparing to the nonsuspected patients, the suspected cases had lower white blood cell count, hemoglobin level, neutrophil count, serum calcium ion level and serum albumin concentration, as well as higher levels of C-reactive protein. All the suspected cases were ruled out of SARS-CoV-2 infection by twice negative tests for the virus. Therefore, the incidence of SARS-CoV-2 infection in hematologic malignancy children was low during the COVID-19 pandemic in China. COVID-19 got early detected and the virus spread out in the ward was effectively blocked by increasing test frequency and using single-room isolation for 5 to 7 days after admission.

Clinicopathological characterisation of myeloproliferative neoplasm-unclassifiable (MPN-U): a retrospective analysis from a large UK tertiary referral centre.

Myeloproliferative neoplasm-unclassifiable (MPN-U) presents an MPN-type phenotype that fails to meet diagnostic criteria for other MPN variants. Variability in the clinicopathological phenotypes presents many challenges. Amongst a registry cohort of 1512 patients with MPN, 82 with MPN-U were included, with a median (range) age of 49·7 (13-79) years. Albeit heterogeneous, common presentation features included raised lactate dehydrogenase, thrombocytosis and clustered/pleomorphic megakaryocytes on trephine biopsy. Thrombosis was common (21%), necessitating vigilance. The median event-free survival was 11·25 years (95% confidence interval 9·3-not reached), significantly shortened in cases with lower platelet counts (<500 × 109 /l) and a leucocytosis (≥12 × 109 /l) at presentation. Generation of potential MPN-U prognostic scores is required.

MASP2 levels are elevated in thrombotic microangiopathies: association with microvascular endothelial cell injury and suppression by anti-MASP2 antibody narsoplimab.

Involvement of the alternative complement pathway (AP) in microvascular endothelial cell (MVEC) injury characteristic of a thrombotic microangiopathy (TMA) is well documented. However, the role of the lectin pathway (LP) of complement has not been explored. We examined mannose-binding lectin associated serine protease (MASP2), the effector enzyme of the LP, in thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome and post-allogeneic hematopoietic stem cell transplantation (alloHSCT) TMAs. Plasma MASP2 and terminal complement component sC5b-9 levels were assessed by enzyme-linked immunosorbent assay (ELISA). Human MVEC were exposed to patient plasmas, and the effect of the anti-MASP2 human monoclonal antibody narsoplimab on plasma-induced MVEC activation was assessed by caspase 8 activity. MASP2 levels were highly elevated in all TMA patients versus controls. The relatively lower MASP2 levels in alloHSCT patients with TMAs compared to levels in alloHSCT patients who did not develop a TMA, and a significant decrease in variance of MASP2 levels in the former, may reflect MASP2 consumption at sites of disease activity. Plasmas from 14 of the 22 TMA patients tested (64%) induced significant MVEC caspase 8 activation. This was suppressed by clinically relevant levels of narsoplimab (1·2 µg/ml) for all 14 patients, with a mean 65·7% inhibition (36.8-99.4%; P < 0·0001). In conclusion, the LP of complement is activated in TMAs of diverse etiology. Inhibition of MASP2 reduces TMA plasma-mediated MVEC injury in vitro. LP inhibition therefore may be of therapeutic benefit in these disorders.

From Budd-Chiari syndrome to acquired von Willebrand syndrome: thrombosis and bleeding complications in the myeloproliferative neoplasms.

Thrombotic and hemorrhagic complications are prevalent in patients with essential thrombocythemia, polycythemia vera, and myelofibrosis. Given the impact on morbidity and mortality, reducing the risk of thrombosis and/or hemorrhage is a major therapeutic goal. Historically, patients have been risk stratified on the basis of traditional factors, such as advanced age and thrombosis history. However, multiple factors contribute to the thrombotic tendency, including gender, mutational profile, inflammatory stress, and abnormal cell adhesion. Management includes cardiovascular risk reduction and use of antiplatelet therapy, depending on myeloproliferative neoplasm subtype and mutational status. Anticoagulation is a mainstay of therapy for those with venous thrombosis, but practice patterns remain heterogeneous. Cytoreduction is indicated for higher-risk patients, but efficacy may depend on the involved vascular bed. Management of special situations, such as unusual site thrombosis, bleeding, the perioperative period, and pregnancy, are especially challenging. In this article, risk factors and treatment strategies for myeloproliferative neoplasm thrombosis and bleeding, including special situations, are reviewed. Insights gained from recent studies may lead to the development of a more precise risk classification and tailored therapy.

Tumour markers with clinically controlled cut-offs for suspected cancer.

BACKGROUND: Due to insufficient scientific evidence, panels of tumour markers (TMs) are currently not recommended for use in suspected cancer. However, recent well-designed studies have revealed a potential clinical value in lung cancer. We analysed the diagnostic accuracy of a panel of 11 circulating TMs with clinically controlled thresholds in the differentiation of cancer from nonmalignant diseases. METHODS: We prospectively recruited 4776 consecutive patients presenting with focal or nonspecific symptoms suggestive of cancer who underwent testing for 11 serum TMs before diagnosis was known. The study abided by 2015 STARD guidelines. Tumour markers included, among others, carbohydrate antigen 19-9, carcinoembryonic antigen, alpha-fetoprotein, squamous cell carcinoma-associated antigen, prostate-specific antigen (males), neuron-specific enolase, progastrin-releasing peptide and carbohydrate antigen 125. Thresholds were adjusted for the presence of kidney failure, liver disease, effusions and dermatological disorders. Results showing ≥1 TMs with concentrations above threshold were considered positive. RESULTS: Benign diseases were diagnosed in 3281 (68.7%) patients and cancer in 1495 (31.3%), with epithelial cancers in 1214 (77% at stage IV). When applying criteria for controlled thresholds, overall specificity was 98%. Overall sensitivity of the panel in epithelial cancers was 72.2%, positive predictive value 93% and negative predictive value 90.5%. The area under the receiver operating characteristic curve was 0.920 (95% confidence interval, 0.902-0.924). CONCLUSIONS: By using clinically controlled cut-offs, the combined panel demonstrated an excellent ability to discriminate epithelial cancers from nonmalignant diseases. However, its use in clinical practice would need formal validation through a multicentre controlled trial assessing a panel-guided strategy vs. standard diagnosis.

Contribution of donor- and recipient-associated factors to allergic transfusion reactions to platelets.

BACKGROUND: Pediatric hematology-oncology patients require frequent platelet transfusions to manage chemotherapy-induced thrombocytopenia, and allergic transfusion reactions (ATRs) are common. Risk for platelet-associated ATRs can result from recipient- or donor-specific factors. STUDY DESIGN AND METHODS: We report a rare case in which an individual platelet donor caused repeated ATRs in multiple recipients. This observation led us to conduct a retrospective study at a pediatric hematology-oncology center to identify donor- and recipient-associated risk factors for ATRs. RESULTS: Single-donor platelets from an individual donor precipitated ATRs in 78.6% (n = 11/14) of recipients and 66.7% (n = 12/18) of platelet transfusions. We found in a cohort of pediatric hematology-oncology patients that 12.6% of recipients and 1.0% of platelet transfusions were associated with ATRs. Recipients who were aged 4 to 18 years, male, and those with central nervous system or solid tumors and with a history of ATRs to platelets were more likely to experience ATRs. Donor-associated risk factors were not identified, and we did not implicate additional donors in our single-center cohort with a frequency of ATRs comparable to the index donor. Based on our findings, we developed a novel statistical model to identify recipients and donors prone to experiencing or mediating ATRs. CONCLUSIONS: Both donors and recipients contribute to ATRs. Identification of high-risk donors and recipients for further scrutiny and potential interventions can improve the safety of platelet transfusions.

Post-transplant ferritin level predicts outcomes after allogeneic hematopoietic stem cell transplant, independent from pre-transplant ferritin level.

Allogeneic hematopoietic stem cell transplantation (HCT) is associated with significant morbidity and mortality. Elevated pre-transplant ferritin level (ferritinPre-HCT) is reported to be associated with increased mortality following HCT. The present study attempted to determine whether post-transplant ferritin level (ferritinPost-HCT) is associated with outcomes post-HCT, especially in the subgroups which developed acute or chronic graft-versus-host disease (GVHD). Out of 229 patients with serum ferritin level measured post-HCT, median ferritinPost-HCT was 2178 ng/mL. Patients were stratified into low- or high-risk groups using recursive partitioning, based on ferritinPost-HCT (≤ 3169 vs > 3169 ng/mL) and ferritinPre-HCT (≤ 669 vs > 669 ng/mL). Compared to the low ferritinPost-HCT group, the high ferritinPost-HCT group had lower 3-year overall survival (OS) (40.0% vs 66.7%, p < 0.001) and higher non-relapse mortality (NRM) (48.6% vs 17.8%, p < 0.001), but no difference in relapse (10.5% vs 19.7%, p = 0.079). Multivariate analysis confirmed ferritinPost-HCT as an independent prognostic factor for OS (p = 0.001, HR = 2.323) and NRM (p < 0.001, HR = 3.905). However, ferritinPre-HCT did not stratify well for OS or NRM. FerritinPost-HCT was also found to be an independent prognostic marker for OS and NRM in the subgroups which developed GVHD. In our cohort, high ferritinPost-HCT levels were significantly associated with decreased OS and increased NRM independent of ferritinPre-HCT or GVHD. Additional studies including larger sample sizes and prospective investigation are warranted to clarify the prognostic significance and pathophysiology of pre- and post-transplant hyperferritinemia.

Evaluation of time to clearance of high-dose methotrexate using the ARK immunoassay in pediatric hematology/oncology patients: A single-center experience.

A retrospective, single-center, observational study evaluated the difference in time to clearance of high-dose methotrexate between the fluorescence polarization immunoassay (FPIA) and ARK methotrexate assay in pediatric hematology/oncology patients. The post-ARK immunoassay group had an increase in clearance time of 33 h/cycle and 31% increase in cycles with delayed clearance. On posthoc analysis, use of an adjusted clearance threshold of <0.15 µmol/L post-ARK immunoassay, as opposed to the traditional <0.1 µmol/L threshold, would have similar incidence of delayed clearance. The ARK immunoassay demonstrated a positive bias compared to the FPIA in clinical practice, which led to an institutional policy change.

Evaluation of Inflammatory Biomarkers in Pediatric Hematology-Oncology Patients With Bloodstream Infection.

Bloodstream infection (BSI) is a serious complication in pediatric hematology-oncology patients. To evaluate the clinical significance of C-reactive protein (CRP), procalcitonin (PCT), albumin, fibrinogen, and D-dimer as potential biomarkers to differentiate among various subtypes of BSIs in pediatric patients with hematologic and oncologic diseases, we retrieved and analyzed the medical records of pediatric hematology-oncology patients diagnosed with BSI at our hospital between January 2016 and December 2017. The demographic (sex and age) and clinical (primary diseases) characteristics, and laboratory test results (white blood cell and absolute neutrophil counts, and serum CRP, PCT, albumin, fibrinogen, and D-dimer levels) were compared between nosocomial and non-nosocomial; neutropenic and non-neutropenic; and Gram-positive and Gram-negative BSI episodes. A total of 125 BSI episodes were included, including 69 (55.2%) nosocomial cases, 94 (75.2%) neutropenic cases, and 49 (39.2%) Gram-positive episodes. Of the 5 potential biomarkers evaluated (CRP, PCT, albumin, fibrinogen, and D-dimer), PCT levels were significantly lower in neutropenic episodes and Gram-positive BSIs (P=0.008 and P=0.001, respectively). At a cutoff value of 0.67 ng/mL, the diagnostic sensitivity, specificity, and positive/negative predictive values of PCT for the differentiation of Gram-positive and Gram-negative bacterial sepsis were 74.2%, 64.6%, 70.8%, and 65.2%, respectively. We concluded that PCT might potentially serve as a biomarker to differentiate between Gram-positive and Gram-negative BSIs in pediatric hematology-oncology patients.

Emergencies in haematology: tumour lysis syndrome.

Tumour lysis syndrome (TLS) is a significant complication of haematologic malignancies and their management. The syndrome consists of laboratory abnormalities either alone (laboratory TLS) or with clinical sequelae including renal failure, seizures, and arrhythmias (clinical TLS). Clinical TLS is a predictor for worse overall morbidity and mortality in cancer patients, but can be prevented. Thus, accurate prognostication is critical to appropriate management of patients at risk for TLS, and incorporates both disease factors (tumour type and burden) and patient factors (baseline renal insufficiency or hyperuricaemia). Strategies to prevent TLS include hydration and allopurinol in low- and intermediate-risk patients and rasburicase in high-risk patients.

Age-related clonal hematopoiesis.

Age-related alterations in the human blood system occur in B cells, T cells, cells of the innate system, as well as hematopoietic stem and progenitor cells (HSPCs). Interestingly, age-related, reduced genetic diversity can be identified at the stem cell level and also independently in B cells and T cells. This reduced diversity is most probably related to somatic mutations or to changes in the microenvironmental niche. Either process can select for specific clones or cause repeated evolutionary bottlenecks. This review discusses the age-related clonal expansions in the human HSPC pool, which was termed in the past age-related clonal hematopoiesis (ARCH). ARCH is defined as the gradual, clonal expansion of HSPCs carrying specific, disruptive, and recurrent genetic variants, in individuals without clear diagnosis of hematological malignancies. ARCH is associated not just with chronological aging but also with several other, age-related pathological conditions, including inflammation, vascular diseases, cancer mortality, and high risk for hematological malignancies. Although it remains unclear whether ARCH is a marker of aging or plays an active role in these various pathophysiologies, it is suggested here that treating or even preventing ARCH may prove to be beneficial for human health. This review also describes a decision tree for the diagnosis and follow-up for ARCH in a research setting.

Plasma level of interleukin-18 and complicated course of febrile neutropenia in hematological patients after intensive chemotherapy.

In search of a biomarker for complicated course of febrile neutropenia (FN), plasma IL-18 was measured in 92 hematological patients after intensive chemotherapy at the beginning of FN (days 0-3). Complicated course was defined as blood culture positivity or septic shock. IL-18 varied according to background hematological malignancy and showed an inverse correlation with leukocyte count. IL-18 was not associated with complicated course of FN, defined as blood culture positivity or septic shock, in the whole study group, but an association was observed on d1 and d2 after the onset of FN in the subgroup of autologous stem cell transplant recipients with non-Hodgkin lymphoma.

Red blood cell and platelet transfusion support in the first 30 and 100 days after allogeneic hematopoietic cell transplant.

BACKGROUND: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients often require substantial but variable transfusion support. STUDY DESIGN AND METHODS: This single-center, retrospective study evaluated the red blood cell (RBC) and platelet (PLT) transfusion data of first-time allo-HSCT recipients transplanted in 2011 to 2017. Multivariate analyses were performed to assess the associations between patient and transplant-related factors and transfusion requirements. RESULTS: The study included 1762 patients who received peripheral blood stem cells (88.2%), marrow (7.0%), or umbilical cord (4.8%) from matched related (38.3%), unrelated (49.2%), or haploidentical (7.8%) donors. Almost all patients required RBCs (88.3%) or PLTs (97.4%) during the first 30 days, with medians of 3 (range, 1-37) RBC and 6 (range, 1-144) PLT units transfused. Fewer patients required RBC (43.8%) or PLT (27.3%) transfusions during Days 31 to 100, but the median (range) numbers of RBC and PLT units remained high at 3 (1-36) and 6 (1-116) among transfused patients. RBC and PLT transfusion independence was reached in medians of 24 (95% confidence interval [CI], 22-26) and 12 (95% CI, 11-12) days, respectively. Haploidentical donor, cord graft, and requiring RBC transfusions in the 10 days before HSCT were the most significant independent factors predictive of increased transfusion requirements. Advanced disease, diagnosis, ABO incompatibility, conditioning intensity, CD34+ cell dose, presence of severe acute graft-vs-host disease, and changes in recommended transfusion triggers were also shown to independently impact transfusion requirements. CONCLUSIONS: This study provided for the first time quantitative and comparative transfusion data on a large contemporary cohort of HSCT recipients, including haploidentical and cord graft recipients, and identified factors predictive of increased transfusions.

Successful prevention of severe allergic transfusion reactions with omalizumab.

BACKGROUND: Allergic transfusion reactions (ATRs) are a common adverse reaction to transfusion therapy and can be potentially fatal. Washing blood products is the most effective strategy for preventing ATRs; however, washed products, especially platelets, are not available at many blood centers. STUDY DESIGN AND METHODS: A 29-year-old female patient with an advanced myelodysplastic/myeloproliferative neoplasm, unclassifiable, developed severe ATRs after four platelet transfusions in a week. She showed no response to premedication with histamines and steroids and still had severe ATRs with the next three platelet transfusions. A laboratory workup revealed that her IgA level was slightly decreased, while her haptoglobin level was normal. Anti-IgA testing was not available. The patient decided to undergo allogeneic peripheral blood stem cell (PBSC) transplantation. As the onset of symptoms ATR, which were similar to Type 1 hypersensitivity reactions mediated by IgE antibodies, occurred immediately after transfusion and omalizumab is a humanized monoclonal anti-IgE, we elected to offer off-label use of omalizumab before administering the conditioning regimen. RESULTS: Omalizumab was injected subcutaneously at a dose of 150 mg. Surprisingly, transfusion reactions fully resolved within 24 hours. No serious side effects were noticed. Another 150 mg of omalizumab was administered 1 day before PBSC infusion. The patient remained asymptomatic without any signs of ATRs throughout the whole period of transplantation. Seven months after transplantation, the patient was in complete remission without overt complications. CONCLUSION: This case suggests that omalizumab is a promising new alternative treatment for the prevention of severe ATRs.

Evaluation of post-thaw CFU-GM: clinical utility and role in quality assessment of umbilical cord blood in patients receiving single unit transplant.

BACKGROUND: The CFU assay is considered the only in vitro assay that assesses the biologic function of hematopoietic stem and progenitor cells (HSPC). STUDY DESIGN AND METHODS: To investigate the impact of post-thaw CFU-GM counts on the quality of umbilical cord blood (UCB), we studied transplant outcomes in 269 patients receiving single UCB transplant. We also correlated the post-thaw CFU-GM counts of 1912 units with the pre-freeze and post-thaw graft characteristics, hoping to optimize selection criteria of UCB. Data analysis included: total nucleated cells, viability, CD34+, nucleated red blood cells (NRBC), hematocrit, frozen storage time, and cord blood bank (CBB). RESULTS: We demonstrated an association between post-thaw CFU-GM dose and the speed of neutrophil and platelet engraftment (p < 0.01). Higher post-thaw CFU-GM dose showed an increased benefit for neutrophil and platelet engraftment (p < 0.01). Post-thaw CD34+ cell dose and CFU-GM dose were strongly correlated (r = 0.78). However, CFU-GM dose showed additional benefit for patients receiving the lowest quartile of CD34+ dose. HLA disparity did not adversely impact either neutrophil or platelet engraftment. Post-thaw CFU-GM/million nucleated cells plated showed moderate correlation with pre-freeze and post-thaw CD34+ and weak correlation with other parameters. Post-thaw CFU-GM was not influenced by storage time, but was impacted by the CBB from which the unit is obtained (p < 0.01). CONCLUSION: Post-thaw CFU-GM is an effective measure of the quality and efficacy of the UCB graft, particularly adding valuable clinical information when the CD34+ cell dose is low. Consideration of pre-freeze CD34+ cell content and CBB as additional selection criteria is warranted.

Viscoelastic testing in oncology patients (including for the diagnosis of fibrinolysis): Review of existing evidence, technology comparison, and clinical utility.

The quantification of the coagulopathic state associated with oncologic and hematologic diseases is imperfectly assessed by common coagulation tests such as prothrombin time, activated partial thromboplastin time, fibrinogen levels, and platelet count. These tests provide a static representation of a component of hemostatic integrity, presenting an incomplete picture of coagulation in these patients. Viscoelastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), as whole blood analyses, provide data related to the cumulative effects of blood components and all stages of the coagulation and fibrinolytic processes. The utility of VETs has been demonstrated since the late 1960s in guiding blood component therapy for patients undergoing liver transplantation. Since then, the scope of viscoelastic testing has expanded to become routinely used for cardiac surgery, obstetrics, and trauma. In the past decade, VETs' expanded usage has been most significant in trauma resuscitation. However, use of VETs for patients with malignancy-associated coagulopathy (MAC) and hematologic malignancies is increasing. For the purposes of this narrative review, we discuss the similarities between trauma-induced coagulopathy (TIC) and MAC. These similarities center on the thrombomodulin-thrombin complex as it switches between the thrombin-activatable fibrinolysis inhibitor coagulation pathway and activating the protein C anticoagulation pathway. This produces a spectrum of coagulopathy and fibrinolytic alterations ranging from shutdown to hyperfibrinolysis that are common to TIC, MAC, and hematologic malignancies. There is expanding literature regarding the utility of TEG and ROTEM to describe the hemostatic integrity of patients with oncologic and hematologic conditions, which we review here.