Prognostic factors in 448 newly diagnosed multiple myeloma receiving bortezomib-based induction: impact of ASCT, transplant refusal and high-risk MM.

In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p = 0.006), international staging system (ISS) 3 (p = 0.003), high lactate dehydrogenase (LDH) (p = 7.6 × 10-7) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p = 2.7 × 10-5) and ASCT (p = 4.8 × 10-4) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p = 1.06 × 10-8, TE-refused p = 0.002) and event free survival (EFS) (TE-unfit p = 0.00013, TE-refused p = 0.002). Among TE patients with ASCT, multivariate analysis showed that age ≥ 60 (p = 8.9 × 10-4), ISS 3 (p = 0.019) and high LDH (p = 2.6 × 10-4) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS 3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high-risk features warrant further studies.

Hepatitis B virus reactivation in seronegative occult hepatitis B patient receiving ibrutinib therapy.

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment for several mature B-cell malignancies. Reactivation of hepatitis B virus (HBV) is a well-described complication in patients with chronic HBV infection or prior HBV exposure undergoing cytotoxic or immunosuppressive chemotherapy for hematologic malignancies. This phenomenon has been frequently reported with rituximab. However, published data on the risk of HBV reactivation induced by ibrutinib are scarce. Cases of HBV reactivation in hematologic patients receiving ibrutinib therapy have recently been described, but limited only to overt hepatitis B patients or seropositive occult hepatitis B patients. CASE PRESENTATION: We report the first case of HBV reactivation during ibrutinib treatment in an asymptomatic 82-year-old woman with seronegative occult hepatitis B patient (i.e., negative for HBsAg, anti-HBc and anti-HBs). Four months after ibrutinib treatment, her liver function test (LFT) was deranged, with seroconversion to HBsAg positivity. Serum hepatitis B virus DNA was quantified to be 1.92 × 108 IU/ml. Antiviral treatment was initiated, and viral load was gradually suppressed with improvement in LFT. CONCLUSIONS: Our case illustrated that in populations with a high incidence of HBV exposure, systematic screening for HBV exposure is essential prior to ibrutinib treatment, followed by serial monitoring of serologic and molecular markers of hepatitis B. There is a need for an international consensus to support the recommendation of antiviral prophylaxis against HBV reactivation in patients using ibrutinib.

Clonal heterogeneity of polymorphic B-cell lymphoproliferative disease, EBV-positive, iatrogenic/immune senescence: implications on pathogenesis and treatment.

BACKGROUND: Epstein Barr virus positive (EBV+) immunodeficiency-associated lymphoproliferative disorders (IA-LPD) are heterogeneous diseases with variable treatment strategies that are not well-defined. CASE PRESENTATION: A 68-year-old woman with systemic lupus erythematosus developed EBV+ B-cell polymorphic lymphoproliferative disease (LPD). Positron emission tomography computed tomography (PET/CT) showed a large nasopharyngeal mass, multiple pulmonary lesions, splenomegaly and disseminated lymphadenopathy. Plasma EBV DNA was grossly elevated to 1.5 × 104 IU/mL. There were three paraproteins. Treatment with O-CHOP (obinutuzumab, cyclophosphamide, adriamycin, vincristine, prednisolone) led to undetectable plasma EBV DNA, suggesting eradiation of the EBV-positive malignant clone. However, radiologic abnormalities were still present on PET/CT, and paraprotein persisted. A nasopharyngeal re-biopsy showed infiltration with EBV-negative plasma cells. On treatment with lenalidomide, she finally achieved complete metabolic response. Molecular analysis showed that the EBV+ B-cell LPD and the EBV- plasma cell lesion exhibited identical immunoglobulin gene rearrangements. Next generation sequencing revealed that the EBV+ B-LPD showed mutation in only one gene (TP53), a profile typical of EBV-driven lymphoid neoplasms. However, the EBV- plasma cell lesion showed mutations in five genes (TP53, SF3B1, STAT5B, CD79B and CRKL), suggesting that these mutations instead of EBV infection were the oncogenic driver. CONCLUSION: The presence of both EBV+ and EBV- lesions, which showed different mutational profiles, indicated clonal heterogeneity that might be of biologic and therapeutic significance.

Bendamustine treatment of haematological malignancies: significant risks of opportunistic viral, fungal and bacterial infections.

OBJECTIVES: Bendamustine is a standard treatment for low-grade B-cell lymphomas, and considered safe in clinical trials. Its safety in routine practice might be different. METHODS: We retrospectively analyzed the infection complications in an unselected cohort of patients treated with bendamustine over a nine-year period. Patients were regularly monitored for blood counts and cytomegalovirus (CMV) reactivation by antigen assay and polymerase chain reaction. They received granulocyte colony stimulating factor for neutropenia, and routine anti-pneumocystis and optional anti-fungal prophylaxis. RESULTS: There were 179 men and 127 women at a median age of 61.5 (20-90) years, 52% receiving bendamustine for relapsed/refractory disease. Malignancies included low-grade B-cell lymphomas (54%), myeloma (10%), T-cell lymphomas (11%), Hodgkin lymphoma (2%) and other lymphoid neoplasms (23%). Most patients had good performance status (Eastern Cooperative Oncology Group score: 0-1, 72%). CMV reactivation occurred in 58 patients (19%) at a median age of 68 (39-85) years. Univariate analysis showed CMV reactivation to be significantly associated with elevated lactate dehydrogenase (P = 0.045), decreased albumin (P = 0.003) and older age (reactivation versus no reactivation: 66.3 ± 11.4 versus 59.4 ± 14.5 years, P = 0.0016). Age remained the only significant risk on multivariate analysis. CMV reactivation resulted in retinitis (N = 4), ependymitis/ventriculitis (N = 1) and duodenitis/colitis (N = 1). Invasive fungal disease occurred in five patients (candidemia, N = 2; aspergillosis N = 1; cryptococcemia, N = 1; scedosporiosis, N-1). Nineteen patients had culture positive septicaemia. CONCLUSION: Our observations showed that even with a vigorous anti-infective strategy, bendamustine treatment was still associated with significant risks of bacterial and opportunistic viral and fungal infections.

The impact of bortezomib-based induction in newly diagnosed multiple myeloma with chromosome 1q21 gain.

Introduction: Bortezomib has been reported to favourably impact the outcomes of t(4;14) and del(17p) in multiple myeloma (MM), but its impact on gain 1q (+1q) is unknown. Methods: To address this, 250 patients treated with bortezomib-based induction were analysed. All myeloma samples had fluorescence in situ hybridization (FISH) performed on CD138-sorted bone marrow aspirate, and plasma cells were analysed using DNA probes specific for the following chromosomal aberrations: del(13q14), del(17p), t(14;16), t(4;14), and +1q. Presence of +1q was defined as the presence of at least three copies of 1q21 at the cut off level of 20% of bone marrow plasma cells. Results: +1q identified in 167 (66.8%) and associated with t(4;14) and high lactate dehydrogenase (LDH). +1q was not associated with response rate but shorter event-free survival (EFS) (median EFS 35 vs 55 months, p = 0.05) and overall survival (OS) (median OS 74 vs 168 months, p = 0.00025). Copy number and clone size did not impact survival. Multivariate analysis showed +1q was an independent adverse factor for OS together with International Staging System (ISS)3, high LDH, del(17p) and t(4;14). When a risk score of 1 was assigned to each independent adverse factor, OS was shortened incrementally by a risk score from 0 to 4. Post-relapse/progression survival was inferior in those with +1q (median 60 vs 118 months, p = 0.000316). Autologous stem cell transplantation (ASCT) improved OS for those with +1q (median OS 96 vs 49 months, p = 0.000069). Conclusion: +1q is an adverse factor for OS in MM uniformly treated with bortezomib-based induction but was partially mitigated by ASCT. A risk scoring system comprising +1q, LDH, high-risk FISH, and ISS is a potential tool for risk stratification in MM.

Eltrombopag as frontline treatment of aplastic anaemia in routine practice: implications on cost and efficacy.

The thrombopoietin mimetic eltrombopag (EPAG) is efficacious in clinical trials of newly diagnosed moderate (M), severe (S) and very severe (vS) aplastic anaemia (AA). Its use in routine practice and resource-constrained settings is not well described. Twenty-five men and 38 women at a median age of 54 (18-86) years with newly diagnosed AA treated consecutively in a 7-year period with EPAG (N = 6), EPAG/cyclosporine (CsA) (N = 33) and EPAG/CsA/anti-thymocyte globulin (ATG) (N = 24) were analyzed. Because EPAG was not reimbursed, peak doses ranged from 25 to 200 mg/day depending on affordability. EPAG/CsA-treated patients were older (median age: 61 years) with less severe AA (MAA, N = 15; SAA, N = 14; vSAA, N = 4), whereas EPAG/CsA/ATG-treated patients were younger (median age: 44 years) with more severe AA (MAA, N = 2; SAA, N = 12, vSAA, N = 10). The overall/trilineage response rates were 83%/50% for EPAG-treated patients; 79%/42% for EPAG/CsA-treated patients and 75%/63% for EPAG/CsA/ATG-treated patients. Adverse events included grade 1 liver derangement (N = 7) and grade 1 dyspepsia (N = 3). The 5-year overall survivals/failure-free survivals were 62%/80% for the entire cohort; 55%/75% for EPAG/CsA-treated patients and 82%/78% for EPAG/CsA/ATG-treated patients. EPAG showed robust efficacy in AA in routine practice. However, EPAG dosage and combinations remain to be optimized for AA of different severities.

Spectrum of B-cell neoplasms associated with immunoglobulin G4-related disease.

Immunoglobulin G4-related disease (IgG4-RD) has rarely been associated with lymphoid neoplasms, the spectrum of which remains unclear. B-cell lymphoid neoplasms (LN) associated with IgG4-RD diagnosed in a 4-year period were analysed. There were five men and three women at a median age of 76.5 (52-90) years; three with synchronous IgG4-RD and LN; three with IgG4-RD preceding LN by 2, 3, and 22 years; and two with LN preceding IgG4-RD by 2.5 and 7 years. All patients presented with disseminated lymphadenopathy. Monoclonal gammopathy of undetermined significance (MGUS)/smouldering multiple myeloma (SMM) was found in three patients, all with an IgGκ paraprotein. Levels of IgGκ and IgG4 correlated. Diffuse large B-cell lymphoma (DLBCL) was found in three patients, with one case showing co-existing lymphoma and IgG4-RD in the same lymph node biopsy. The remaining two cases were marginal zone lymphoma (MZL) developing in a lacrimal gland previously involved by IgG4-RD; and nodular lymphocyte predominant Hodgkin lymphoma (NLP-HL) diagnosed in a lymph node with concomitant IgG4-RD. Low-dose continuous prednisolone was given for MGUS/SMM, with both monoclonal IgGκ and IgG4 responding. Combination chemotherapy was given for DLBCL, with two patients achieving complete response and one patient dying from refractory lymphoma. The patient with MZL refused treatment, whereas the case of NLP-HL responded completely to chemotherapy. Our findings together with previous observations suggest that IgG4-RD has an increased risk of B-cell neoplasms. Patients with IgG4-RD presenting with lymphadenopathy require vigorous investigations to exclude lymphoid neoplasms.

Ruxolitinib in the management of steroid-resistant/-dependent acute and chronic graft-versus-host disease: results of routine practice in an academic centre.

Graft-versus-host disease (GVHD) is an important complication after allogeneic haematopoietic stem cell transplantation (HSCT). Corticosteroids are the standard first-line treatment. Steroid-resistant/-dependent (SR/D) acute and chronic GVHD (aGVHD, cGVHD) lead to significant morbidity/mortality. The JAK2 inhibitor ruxolitinib has recently been shown in clinical trials to be effective in SR/D aGVHD and cGVHD. We retrospectively analysed the efficacy and safety of ruxolitinib in a cohort of SR/D aGVHD and cGVHD patients treated in a non-trial setting. In the aGVHD cohort, there were 14 men and 12 women, median age at 38 (19-63) years. At day 28 post-ruxolitinib, the overall response rate (ORR) was 86% (complete response, CR, 36%; partial response, PR, 50%). Continued ruxolitinib beyond day 28 resulted in a final CR of 68%. However, 3/15 (20%) of CR patients developed cGVHD. In the cGVHD cohort, there were 16 men and 15 women, median age at 33 (21-64) years. The ORR, CR and PR rates changed with continued ruxolitinib treatment, being 86%, 17% and 69% at 1 month; 79%, 38% and 41% at 3 months; and 83%, 52% and 31% at 6 months. Five patients had overlap GVHD, four of whom achieved CR. Multivariate analysis showed that superior overall survival and failure-free survival were associated with CR at day 28 for aGVHD, and CR at 1 year for cGVHD. Ruxolitinib treatment was efficacious for SR/D aGVHD and cGVHD, and continued treatment for at least 6 months was needed to maximize benefit.

Low-dose pembrolizumab and nivolumab were efficacious and safe in relapsed and refractory classical Hodgkin lymphoma: Experience in a resource-constrained setting.

The efficacy and safety of low-dose anti-PD1 antibodies in relapsed/refractory classical Hodgkin lymphoma (cHL) require confirmation. Pembrolizumab (100 mg every 3 weeks, Q3W) or nivolumab (40 mg Q2W) were administered to patients with relapsed/refractory cHL. In the pembrolizumab cohort (N = 11), who had failed a median of three (1-6) therapies (brentuximab vedotin [BV]: 91%; autologous hematopoietic stem cell transplantation [auto-HSCT]: 18%), the overall response rate (ORR) by positron emission tomography-computed tomography was 100% (metabolic complete response [mCR]: 73%; partial response [PR]: 27%). Median cumulative dose for achieving best response was 400 (300-800) mg. Median progression-free survival (PFS) was 35 months. Median overall survival (OS) was not reached. Adverse events (AEs) of grade 1-2 were observed in three patients. In the nivolumab cohort (N = 6), who had failed a median of three (2-6) therapies (BV: 50%; auto-HSCT: 17%; allogeneic HSCT: 34%), the ORR was 100% (mCR: 67%; PR: 17%; indeterminate response: 17%). Median cumulative dose for achieving best response was 160 (160-360) mg. Median PFS was 33 months. Median OS was not reached. AEs of grade 1-2 were observed in four patients, two of whom had pre-existing autoimmune conditions. Five patients with Epstein-Barr virus (EBV) positive Reed-Sternberg cells underwent monitoring of plasma EBV DNA, which became negative in four mCR patients but remained positive in one PR patient who died ultimately from refractory lymphoma. Low-dose pembrolizumab and nivolumab were highly efficacious and safe in relapsed/refractory cHL. These observations have significant financial implications in resource-constrained settings.

Risk assessment of venous thromboembolism in hematological cancer patients: a review.

Introduction: Venous thromboembolism (VTE) is a frequent and serious complication in cancer patients. Nonetheless, patients with hematological cancers receive less attention as compared with their solid tumor counterparts regarding this potentially fatal complication.Areas covered: Risk factors that are associated with the development of VTE in hematological cancers are discussed, based on a PubMed literature search. Since different hematological malignancies carry different risks of VTE, risk assessment in individual types of hematological cancers, including acute leukemias, lymphomas, myeloma, and myeloproliferative neoplasms are examined separately. Clinical relevance of VTE assessment and current guidelines on thromboprophylaxis in patients with hematological malignancies are also briefly reviewed.Expert opinion: When assessing VTE risk in patients with hematological cancers, in addition to the non-cancer specific risk factors, individual cancer-type-specific and the therapy-related factors must be taken into consideration. Primary thromboprophylaxis should be considered in high-risk patients.

Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation.

Clofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18- to 65-year-old AML patients refractory to first-line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high-dose cytarabine consolidation, with clofarabine (30 mg/m2 /d, Days 1-5), cytarabine (750 mg/m2 /d, Days 1-5), and mitoxantrone (12 mg/m2 /d, Days 3-5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mutational profile of a 69-gene panel was evaluated. Twenty-six men and 26 women at a median age of 46 (22-65) years were treated. The overall response rate after the first cycle of CLAM was 90.4% (complete remission, CR: 69.2%; CR with incomplete hematologic recovery, CRi: 21.2%). Twenty-two CR/CRi patients underwent allo-HSCT. The 2-year overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were 65.8%, 45.7%, and 40.2%, respectively. Multivariate analyses showed that superior OS was associated with CR after CLAM (P = .005) and allo-HSCT (P = .005), and superior RFS and EFS were associated with allo-HSCT (P < .001). Remarkably, CR after CLAM and allo-HSCT resulted in 2-year OS of 84.3% and 90%, respectively. Karyotypic aberrations and genetic mutations did not influence responses or survivals. Grade 3/4 neutropenia/thrombocytopenia and grade 3 febrile neutropenia occurred in all cases. Other nonhematologic toxicities were mild and uncommon. There was no treatment-related mortality and the performance of allo-HSCT was not compromised. Clofarabine, cytarabine, and mitoxantrone was highly effective and safe in refractory/relapsed AML. This study was registered at ClinicalTrials.gov (NCT02686593).

Oral arsenic trioxide incorporation into frontline treatment with all-trans retinoic acid and chemotherapy in newly diagnosed acute promyelocytic leukemia: A 5-year prospective study.

BACKGROUND: Strategies using oral arsenic trioxide (As2 O3 ) are efficacious in relapsed acute promyelocytic leukemia (APL), but they have not been examined in newly diagnosed cases. METHODS: Sixty-two consecutive patients (24 men and 38 women) with a median age of 52 years (range, 22-85 years), 36% of whom had high-risk features, underwent induction with all-trans retinoic acid at 45 mg/m2 /d, oral As2 O3 at 10 mg/d, and ascorbic acid at 1 g/d (the all-trans retinoic acid-arsenic trioxide-ascorbic acid [AAA] regimen) for 6 weeks (with patients younger than 70 years additionally receiving daunorubicin at 50 mg/m2 /d × 3); they then underwent consolidation with 2 monthly cycles of daunorubicin (50 mg/m2 /d × 2) and cytarabine (100 mg/m2 /d × 5) and received AAA maintenance (2 weeks every 8 weeks) for 2 years. A contemporaneous cohort of 37 newly diagnosed patients (15 men and 22 women) with a median age of 51 years (range, 23-78 years), not consenting to oral As2 O3 induction but receiving similar induction, consolidation, and AAA maintenance, served as a comparator group; 46% of these patients had high-risk features. RESULTS: The oral As2 O3 induction cohort showed a complete remission (CR) rate of 100%. After a median of 37 months (range, 13-82 months), there were no relapses, so conventional risks (age, leukocyte and platelet counts, and Fms-like tyrosine kinase 3 [FLT3] mutations) were not relevant. The leukemia-free survival (LFS) and overall survival (OS) rates were 100% at 3 years and 94.1% at 5 years. The non-As2 O3 induction cohort showed a CR rate of 100%. After a median of 52 months (range, 14-77 months), there were 3 relapses (8%). Comparable patients in the oral As2 O3 induction and non-As2 O3 induction cohorts showed similar OS, but LFS was significantly superior in the oral As2 O3 induction cohort. CONCLUSIONS: The incorporation of oral As2 O3 into induction for newly diagnosed APL was safe and decreased relapses.

Monitoring and Treatment of Patients Undergoing Immunotherapy With Anti-CD20 Who are Exposed to HBV.

Reactivation of hepatitis B virus (HBV) is a potentially fatal complication of immunosuppressive therapy, and can occur in individuals who are hepatitis B surface antigen (HBsAg) negative but positive for hepatitis B core antibody (anti-HBc). While anti-HBc positivity indicates prior HBV exposure, it may also reflect clearance of HBsAg, but with viral persistence at low intrahepatic replicative and transcriptional levels.1 HBV reactivation can still occur during intense immunosuppression, including B cell-depleting therapy with anti-CD20 antibodies2 and hematopoietic stem cell transplantation.3 While prevention via antiviral prophylaxis is recommended, it remains uncertain, from a global perspective, if this is an ideal and cost-effective strategy. An alternative is regular HBV DNA monitoring.4 However, this approach is problematic in resource-constrained regions, where the logistics of sample collection, transportation, and molecular analysis in dedicated facilities poses challenges.5 We aimed to evaluate the effectiveness of simple monitoring strategies using routine liver biochemistry and serum HBsAg in preventing HBV-related complications during anti-CD20 therapy.

Long-term outcome of relapsed acute promyelocytic leukemia treated with oral arsenic trioxide-based reinduction and maintenance regimens: A 15-year prospective study.

BACKGROUND: For patients who have acute promyelocytic leukemia (APL) in second complete remission (CR2), optimal postremission strategies remain undefined. METHODS: The role of an oral arsenic trioxide (As2 O3 )-based regimen in the management of patients who had APL in CR2 was examined. RESULTS: Seventy-three patients with APL in first relapse (R1) were studied. Oral As2 O3 -based reinduction resulted uniformly in CR2, irrespective of previous As2 O3 exposure. All patients received oral As2 O3 -based maintenance in CR2. At a median follow-up of 94 months (range, 9-205 months), 43 patients (58.9%) were still in CR2, and 49 (67.1%) had finished the planned 2-year CR2 maintenance with all-trans retinoic acid, oral As2 O3 , and ascorbic acid. Reinduction and maintenance treatments were well tolerated. Grade 1 and 2 headache occurred in 20 patients (27.4%). Hepatotoxicity, all in the form of transaminitis, occurred in 35 patients (47.9%; grade 1 and 2, n = 26; grade 3 and 4, n = 9). Three patients had self-limiting QTc prolongation. The 10-year leukemia-free survival rate was 56.8%. Thirty patients developed R2. Oral As2 O3 -based reinduction led to CR3 in 27 patients (90%). Post-CR3 strategies included autologous hematopoietic stem cell transplantation and oral As2 O3 maintenance. At a post-CR3 follow-up of 30 months (range, 3-166 months), 11 patients were still in CR3. The 5-year and 10-year overall survival rates in the R1 cohort were 79.5% and 67.3%, respectively. Prior receipt of oral As2 O3 maintenance in CR1 was the only risk factor for inferior leukemia-free survival. Central nervous system involvement occurred in 15 patients, including 5 who remained alive. Relapse during oral As2 O3 therapy was the only significant risk factor for central nervous system involvement. CONCLUSIONS: For patients with relapsed APL, As2 O3 remained effective despite repeated As2 O3 exposures. Oral As2 O3 maintenance was an effective postremission strategy for CR2. Cancer 2018;124:2316-26. © 2018 American Cancer Society.

Eltrombopag in the management of aplastic anaemia: real-world experience in a non-trial setting.

OBJECTIVE: The thrombopoietin mimetic eltrombopag has been used in clinical trials for the frontline and salvage treatment of aplastic anaemia (AA). Eltrombopag was investigated in AA patients on a non-trial all-comer basis. METHODS: Consecutive newly diagnosed and relapsed/refractory AA patients were treated with eltrombopag. RESULTS: In a 4.5-year period, 20 consecutive AA patients (newly diagnosed, N = 10; relapsed/refractory, N = 10) at a median age of 47 (22-84) years were treated with eltrombopag. For newly diagnosed patients, the frontline use of eltrombopag (concomitant medications: anti-thymocyte globulin, ATG, and ciclosporin, N = 4; ciclosporin, N = 5; nil, N = 1) at a median maximum dose of 150 (50-300) mg/day led to an overall response rate (ORR) of 90% (trilineage: 60%; neutrophil: 20%; platelet: 10%). After a median follow-up of 47 (14-179) weeks, responses were maintained in all cases. In relapsed/refractory patients, eltrombopag at a median maximum dose of 150 (50-300) mg/day led to an ORR of 50% (trilineage: 40%; neutrophil: 10%), with responses maintained after a median follow-up of 115 (53-253) weeks. Adverse effects included reversible skin pigmentation (observed in all patients taking eltrombopag at ≥150 mg/day), dyspepsia, and liver function derangement. CONCLUSION: In a routine haematological practice, the use of eltrombopag in AA patients was feasible, safe, and associated with very favourable responses.

Japanese Encephalitis Virus Transmitted Via Blood Transfusion, Hong Kong, China.

Japanese encephalitis virus (JEV) is a mosquitoborne virus endemic to China and Southeast Asia that causes severe encephalitis in <1% of infected persons. Transmission of JEV via blood transfusion has not been reported. We report transmission of JEV via blood donation products from an asymptomatic viremic donor to 2 immunocompromised recipients. One recipient on high-dose immunosuppressive drugs received JEV-positive packed red blood cells after a double lung transplant; severe encephalitis and a poor clinical outcome resulted. JEV RNA was detected in serum, cerebrospinal fluid, and bronchoalveolar lavage fluid specimens. The second recipient had leukemia and received platelets after undergoing chemotherapy. This patient was asymptomatic; JEV infection was confirmed in this person by IgM seroconversion. This study illustrates that, consistent with other pathogenic flaviviruses, JEV can be transmitted via blood products. Targeted donor screening and pathogen reduction technologies could be used to prevent transfusion-transmitted JEV infection in highly JEV-endemic areas.