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1.
Virol J ; 20(1): 168, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37528444

ABSTRACT

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.


Subject(s)
Hepatitis B virus , Hepatitis B , Humans , Female , Aged, 80 and over , Hepatitis B virus/genetics , Hepatitis B Surface Antigens , Hepatitis B/complications , Hepatitis B/drug therapy , Hepatitis B Antibodies , Antiviral Agents/adverse effects , Virus Activation , DNA, Viral
2.
Ann Hematol ; 101(1): 99-108, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34767055

ABSTRACT

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.


Subject(s)
Hodgkin Disease/complications , Immunoglobulin G4-Related Disease/complications , Lymphadenopathy/complications , Lymphoma, B-Cell, Marginal Zone/complications , Lymphoma, Large B-Cell, Diffuse/complications , Monoclonal Gammopathy of Undetermined Significance/complications , Aged , Aged, 80 and over , Disease Management , Female , Hodgkin Disease/therapy , Humans , Immunoglobulin G , Immunoglobulin G4-Related Disease/therapy , Lymphadenopathy/therapy , Lymphoma, B-Cell, Marginal Zone/therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Middle Aged , Monoclonal Gammopathy of Undetermined Significance/therapy
3.
Ann Hematol ; 101(1): 155-163, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34767056

ABSTRACT

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.


Subject(s)
Graft vs Host Disease/drug therapy , Nitriles/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Acute Disease , Adult , Chronic Disease , Female , Graft vs Host Disease/epidemiology , Humans , Janus Kinase 2/antagonists & inhibitors , Male , Middle Aged , Retrospective Studies , Steroids/therapeutic use , Survival Analysis , Young Adult
4.
Ann Hematol ; 101(6): 1163-1172, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35412083

ABSTRACT

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.


Subject(s)
Anemia, Aplastic , Adolescent , Adult , Aged , Aged, 80 and over , Anemia, Aplastic/chemically induced , Anemia, Aplastic/drug therapy , Antilymphocyte Serum/therapeutic use , Benzoates/adverse effects , Cyclosporine/therapeutic use , Female , Humans , Hydrazines/adverse effects , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Pyrazoles , Treatment Outcome , Young Adult
5.
Hematol Oncol ; 38(5): 726-736, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32786092

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Drug Resistance, Neoplasm , Female , Hodgkin Disease/diagnosis , Hodgkin Disease/mortality , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local , Neoplasm Staging , Nivolumab/administration & dosage , Positron Emission Tomography Computed Tomography , Retreatment , Retrospective Studies , Survival Analysis , Treatment Outcome , Young Adult
6.
Cancer ; 125(17): 3001-3012, 2019 09 01.
Article in English | MEDLINE | ID: mdl-31090936

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Promyelocytic, Acute/drug therapy , Administration, Oral , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Arsenic Trioxide/administration & dosage , Female , Humans , Leukemia, Promyelocytic, Acute/mortality , Male , Middle Aged , Prospective Studies , Treatment Outcome , Tretinoin/administration & dosage , Young Adult
7.
Clin Gastroenterol Hepatol ; 17(7): 1410-1412, 2019 06.
Article in English | MEDLINE | ID: mdl-30243760

ABSTRACT

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.


Subject(s)
Antigens, CD20/immunology , Hepatitis B virus/physiology , Hepatitis B, Chronic/therapy , Immunotherapy/methods , Monitoring, Physiologic/methods , Rituximab/therapeutic use , Aged , DNA, Viral/analysis , Female , Follow-Up Studies , Hepatitis B Antibodies/analysis , Hepatitis B Surface Antigens/analysis , Hepatitis B, Chronic/virology , Humans , Immunologic Factors/therapeutic use , Male , Middle Aged , Prognosis , Prospective Studies , Virus Activation
8.
Emerg Infect Dis ; 24(1)2018 01.
Article in English | MEDLINE | ID: mdl-29043965

ABSTRACT

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.


Subject(s)
Blood Transfusion , Encephalitis Virus, Japanese , Encephalitis, Japanese/transmission , Disease Outbreaks , Encephalitis Virus, Japanese/genetics , Encephalitis, Japanese/diagnostic imaging , Encephalitis, Japanese/epidemiology , Hong Kong/epidemiology , Humans , Immunocompromised Host , Magnetic Resonance Imaging , Male , Middle Aged , Neuroimaging , Phylogeny , Polymerase Chain Reaction , Sequence Analysis, DNA
9.
Cancer ; 124(11): 2316-2326, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29579321

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Arsenic Trioxide/administration & dosage , Leukemia, Promyelocytic, Acute/therapy , Neoplasm Recurrence, Local/therapy , Remission Induction/methods , Administration, Oral , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Arsenic Trioxide/adverse effects , Ascorbic Acid/administration & dosage , Ascorbic Acid/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Combined Modality Therapy/methods , Disease-Free Survival , Female , Headache/chemically induced , Headache/diagnosis , Headache/epidemiology , Hematopoietic Stem Cell Transplantation , Hong Kong/epidemiology , Humans , Leukemia, Promyelocytic, Acute/mortality , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Prospective Studies , Risk Factors , Severity of Illness Index , Survival Analysis , Time Factors , Transplantation, Autologous , Tretinoin/administration & dosage , Tretinoin/adverse effects , Young Adult
10.
Hepatology ; 65(5): 1451-1461, 2017 May.
Article in English | MEDLINE | ID: mdl-28027590

ABSTRACT

Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (HSCT) has not been prospectively studied. HBsAg-negative, anti-HBc-positive patients with undetectable HBV DNA undergoing allogeneic HSCT were prospectively monitored every 4 weeks. The primary endpoint was HBV reactivation, defined as detectable HBV DNA (≥10 IU/mL). Secondary endpoints included overall survival, HBsAg positivity, and changes in liver biochemistry and antibody to HBsAg levels. Among 297 allogeneic HSCT recipients, 85 (28.7%) were HBsAg-negative, anti-HBc-positive, of whom 62 were recruited and monitored for a median of 48 (4-104) weeks. The 2-year cumulative HBV DNA detectability rate was 40.8%, occurring at a median of 44 (8-100) weeks. Multivariate analysis showed that age ≥50 years (P = 0.004, hazard ratio = 8.2) and chronic graft-versus-host disease (P = 0.010, hazard ratio = 5.3) were significantly associated with HBV reactivation. Other clinical parameters, including baseline antibody to HBsAg status, serial changes in antibody to HBsAg levels, and donor serology, were not associated with HBV reactivation. Patients <50 years old and without chronic graft-versus-host disease, compared with the remaining patient cohort, had a significantly lower 2-year cumulative HBV reactivation rate (5.6% versus 65.0%, P = 0.004). Entecavir successfully suppressed HBV DNA to undetectable levels, with no cases developing biochemical hepatitis. CONCLUSION: HBsAg-negative, anti-HBc-positive patients had a high rate of HBV reactivation after allogeneic HSCT, with determinants of HBV reactivation including age ≥50 years and chronic graft-versus-host disease; treatment strategies based on these parameters may prevent HBV reactivation and subsequent complications. (ClinicalTrials.gov identifier NCT01481649.) (Hepatology 2017;65:1451-1461).


Subject(s)
Hematopoietic Stem Cell Transplantation , Hepatitis B virus/physiology , Hepatitis B, Chronic/immunology , Postoperative Complications/immunology , Virus Activation , Adult , Age Factors , Antiviral Agents/therapeutic use , Female , Graft vs Host Disease/complications , Guanine/analogs & derivatives , Guanine/therapeutic use , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Humans , Male , Middle Aged , Postoperative Complications/drug therapy , Postoperative Complications/virology , Prospective Studies , Recurrence , Young Adult
12.
Am J Gastroenterol ; 111(12): 1788-1795, 2016 12.
Article in English | MEDLINE | ID: mdl-27644733

ABSTRACT

OBJECTIVES: Hepatitis B core-related antigen (HBcrAg) is a novel serum marker that correlates with intrahepatic hepatitis B virus (HBV) activity. Its association with HBV reactivation in hepatitis B surface antigen (HBsAg)-negative antibody to hepatitis B core antigen (anti-HBc)-positive patients undergoing high-risk immunosuppressive therapy is undefined. METHODS: HBcrAg was measured in HBsAg-negative, anti-HBc-positive Asian patients with undetectable HBV DNA, who participated in two prospective studies investigating HBV reactivation during rituximab-containing chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Patients were monitored every 4 weeks for up to 2 years, with entecavir started when HBV reactivation, defined as HBV DNA ≥10 IU ml-1, developed. RESULTS: One hundred and twenty-four HBsAg-negative, anti-HBc-positive patients (rituximab, N=62; allogeneic HSCT, N=62) with a median follow-up of 64 weeks (range: 4-104 weeks) were studied. HBV reactivation occurred in 31 patients, with a 2-year cumulative reactivation rate of 40.4%. Serum HBcrAg was detected in 43 (34.7%) patients. Baseline HBcrAg positivity was significantly associated with HBV reactivation (P=0.004, hazard ratio (HR): 2.94, 95% confidence interval (95% CI): 1.43-6.07). HBcrAg-positive patients had a significantly higher 2-year HBV reactivation rate than HBcrAg-negative patients (71.8 vs. 31%, P=0.002). In the rituximab cohort, the HRs for positive HBcrAg and negative antibody to HBsAg for HBV reactivation were 3.65 and 2.84, respectively (P=0.011, 95% CI: 1.35-9.86 and P=0.032, 95% CI: 1.10-7.37, respectively). CONCLUSIONS: Serum HBcrAg positivity is a significant risk factor of HBV reactivation in HBsAg-negative, anti-HBc-positive patients undergoing high-risk immunosuppressive therapy and can potentially have a role in identifying patients who will best benefit from prophylactic nucleoside analogue treatment.


Subject(s)
Antineoplastic Agents/adverse effects , Carrier State/immunology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Hepatitis B Core Antigens/blood , Hepatitis B, Chronic/immunology , Rituximab/adverse effects , Virus Activation , Adult , Aged , Aged, 80 and over , Asian People , DNA, Viral/blood , Female , Follow-Up Studies , Hepatitis B Antibodies/immunology , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Humans , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Transplantation, Homologous , Young Adult
14.
Echocardiography ; 33(9): 1361-7, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27158922

ABSTRACT

BACKGROUND: The new three-dimensional speckle tracking echocardiography (3DSTE) may enable comprehensive quantification of global left ventricular (LV) myocardial mechanics. METHODS: Twenty-four patients aged 29.3 ± 5.2 years and 22 controls were studied. 3DSTE was performed to assess LV 3D global strain, twist and torsion, ejection fraction, and systolic dyssynchrony index (SDI). The LV SDI was calculated as % of SD of times-to-peak strain of 16 segments/RR interval. The global performance index (GPI) was calculated as (global 3D strain·torsion)/SDI. Area under the receiver operating characteristic curve (AUC) was calculated to determine the capability of 3DSTE parameters to discriminate between patients with (cardiac magnetic resonance T2* <20 ms) and those without myocardial iron overload. RESULTS: Compared with controls, patients had significantly lower LV global 3D strain (P < 0.001), twist (P = 0.01), torsion (P = 0.04), and ejection fraction (P < 0.001) and greater SDI (P < 0.001). The GPI was lower in patients than controls (P < 0.001). T2* value correlated positively with global 3D strain (r = 0.74, P < 0.001) and GPI (r = 0.63, P = 0.001), and negatively with SDI (r = -0.44, P = 0.03). The AUCs of GPI, global 3D strain, ejection fraction, torsion, and 1/SDI were 0.94, 0.90, 0.87, 0.82, and 0.70, respectively. The GPI cutoff of 2.7°/cm had a sensitivity of 94.9% and a specificity of 88.9% of differentiating patients with from those without myocardial iron overload. CONCLUSIONS: The LV composite index of strain, torsion, and dyssynchrony derived from 3DSTE enables sensitive detection of myocardial iron overload in patients with thalassemia.


Subject(s)
Echocardiography, Three-Dimensional/methods , Elasticity Imaging Techniques/methods , Image Interpretation, Computer-Assisted/methods , Iron Overload/diagnostic imaging , Ventricular Dysfunction, Left/diagnostic imaging , beta-Thalassemia/diagnostic imaging , Adult , Female , Humans , Iron Overload/etiology , Male , Reproducibility of Results , Sensitivity and Specificity , Stroke Volume , Ventricular Dysfunction, Left/etiology , beta-Thalassemia/complications
15.
Ann Hematol ; 94(6): 1043-7, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25572171

ABSTRACT

Cytomegalovirus (CMV) retinitis is exceptionally rare outside the clinical context of acquired immunodeficiency syndrome and organ allografting. In a population where seropositivity for past CMV infection exceeded 90 %, CMV retinitis was observed in five of 138 patients (3.6 %) receiving fludarabine-containing regimens together with rituximab, which was significantly more frequent than in 141 patients receiving fludarabine-containing regimens alone, where no case was observed (P = 0.029). Treatment of CMV retinitis comprised both intravitreal and systemic ganciclovir/foscarnet. Upon recovery, secondary retinal atrophy occurred in all patients, leading to blindness in 86 % of affected eyes. CMV retinitis is an important complication in patients receiving concomitant rituximab and fludarabine-containing regimens.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antibodies, Monoclonal, Murine-Derived/adverse effects , Cytomegalovirus Retinitis/chemically induced , Cytomegalovirus Retinitis/drug therapy , Vidarabine/analogs & derivatives , Adult , Aged , Cytomegalovirus Retinitis/diagnosis , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Rituximab , Vidarabine/administration & dosage , Vidarabine/adverse effects
16.
Ann Hematol ; 93(3): 493-8, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23949318

ABSTRACT

The frequency of breakthrough invasive fungal diseases (IFDs) during echinocandin therapy is unclear. We retrospectively analyzed 534 hematologic patients treated with echinocandin (caspofungin, N = 55; micafungin, N = 306; anidulafungin, N = 173). Four proven IFDs were found, caused by Candida parapsilosis (N = 2), C. parapsilosis and Candida glabrata (N = 1), and Fusarium species (N = 1). Four cases of possible IFDs were observed, all showing pulmonary infection. One case showed features suggestive of hepatosplenic candidiasis. Six of these eight cases had previously received the purine analog clofarabine. Breakthrough IFD during echinocandin treatment occurred infrequently (1.5 %), caused predominantly by Candida species. Clofarabine usage was an important risk factor.


Subject(s)
Antibiotic Prophylaxis , Candida/drug effects , Candidiasis, Invasive/prevention & control , Echinocandins/therapeutic use , Fusariosis/prevention & control , Fusarium/drug effects , Hematologic Diseases/immunology , Lipopeptides/therapeutic use , Adenine Nucleotides/adverse effects , Adenine Nucleotides/therapeutic use , Adult , Anidulafungin , Antifungal Agents/therapeutic use , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/therapeutic use , Arabinonucleosides/adverse effects , Arabinonucleosides/therapeutic use , Candida/immunology , Candida/isolation & purification , Candidiasis, Invasive/epidemiology , Candidiasis, Invasive/immunology , Candidiasis, Invasive/virology , Caspofungin , China/epidemiology , Clofarabine , Cohort Studies , Cross Infection/epidemiology , Cross Infection/immunology , Cross Infection/prevention & control , Cross Infection/virology , Fusariosis/epidemiology , Fusariosis/immunology , Fusariosis/virology , Fusarium/immunology , Fusarium/isolation & purification , Hematologic Diseases/complications , Hematologic Diseases/therapy , Hematologic Diseases/virology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunocompromised Host , Lung Diseases, Fungal/epidemiology , Lung Diseases, Fungal/immunology , Lung Diseases, Fungal/prevention & control , Lung Diseases, Fungal/virology , Micafungin , Retrospective Studies , Risk Factors
17.
Bone Marrow Transplant ; 59(5): 660-669, 2024 May.
Article in English | MEDLINE | ID: mdl-38383715

ABSTRACT

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.


Subject(s)
Bortezomib , Multiple Myeloma , Transplantation, Autologous , Humans , Multiple Myeloma/therapy , Multiple Myeloma/mortality , Multiple Myeloma/drug therapy , Bortezomib/therapeutic use , Male , Female , Middle Aged , Adult , Aged , Hematopoietic Stem Cell Transplantation/methods , Prognosis
19.
Am J Hematol ; 88(6): 485-91, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23512868

ABSTRACT

Acute leukemia relapsing after allogeneic hematopoietic stem cell transplantation (HSCT) has dismal outcome. Consecutive consenting patients (acute myeloid leukemia: N = 71; acute lymphoblastic leukemia: N = 37), at a median age of 37 (16-57) years, who had relapsed 7.9 (1.3-132) months post-HSCT, were treated with three cytarabine-based intensive regimens as reduced-intensity conditioning (RIC), followed by infusion of mobilized HSC from the original donors. There were four treatment-related mortalities (TRMs). Of 104 evaluable cases, 72 patients (67%) achieved complete remission (CR)/CR with incomplete hematologic recovery (CRi). The median overall survival (OS) of the entire cohort was 11.6 months. The OS of patients achieving CR/CRi after the first RIC/HSCT was 18.8 months, as compared with 3.9 months for those not (P < 0.01). For 32 patients with nonremission, 11 received a repeat RIC-HSCT, leading to CR/CRi in three cases. Therefore, 75/108 (69%) of patients achieved CR/CRi after one or two courses of RIC-HSCT. Among CR/CRi patients, 48 cases relapsed again after 6.1 (1.0-64.4) months. Thirty cases received a repeat RIC-HSCT, leading to CR/CRi in 22 patients. Multivariate analyses showed a significant impact of remission duration after initial HSCT (P = 0.026) and the presence of acute graft-versus-host disease after RIC-HSCT (P = 0.011) on CR/CRi. RIC-HSCT as primary treatment for acute leukemic relapses post-HSCT induced a high CR rate with low TRM. Optimal postremission treatment remains to be defined.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Leukemia/surgery , Transplantation Conditioning/methods , Adolescent , Adult , Cohort Studies , Cytarabine/administration & dosage , Disease-Free Survival , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization/methods , Humans , Leukemia/drug therapy , Leukemia/pathology , Male , Middle Aged , Recurrence , Transplantation, Homologous , Young Adult
20.
Ann Hematol ; 96(7): 1219-1220, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28434018
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