Joycelyn Sim

Pernicious anemia in Chinese : A study of 181 patients in a Hong Kong hospital

Abstract: To study the clinical and hematologic features of pernicious anemia in Chinese, we describe 181 Chinese with megaloblastic anemia and low serum cobalamin, in association with either classic Schilling test results (82 patients) or the presence of serum antibody to intrinsic factor (99 patients), encountered in a regional hospital in Hong Kong from May 1994 to May 2005. The median age was 75 years (range, 32-95 yr) and the male to female ratio was 1:1.5. The chief presenting feature was anemia, and fewer than 10% of patients presented predominantly with neurologic deficit. Gastric biopsies of 109 patients showed glandular atrophy in 73, endocrine cell hyperplasia in 5, polyps in 14, adenocarcinoma in 1, and chronic gastritis in the rest. Gastric adenocarcinoma occurred in 1.7% of patients after a median follow-up of 35 months (range, 0.5-132 mo). Diabetes mellitus occurred in 24% of patients and thyroid disease in 7%. No specific ABO blood group was associated with pernicious anemia. Serum antibody to intrinsic factor (73%) occurred more frequently than serum antibody to gastric parietal cell (65%) (p = 0.353). The frequency of serum antibody to gastric parietal cell was higher in male (78%) than in female patients (53%) (p = 0.018). Pernicious anemia is a major cause of megaloblastic anemia in Chinese. Abbreviations: Hb = hemoglobin; GPC = gastric parietal cell; IF = intrinsic factor; MCV = mean corpuscular volume; PA = pernicious anemia.

Treatment outcome and prognostic factor analysis in transplant-eligible Chinese myeloma patients receiving bortezomib-based induction regimens including the staged approach, PAD or VTD

BackgroundWe have reported promising outcomes using a staged approach, in which bortezomib/thalidomide/dexamethasone was used only in 14 patients with suboptimal response to VAD (vincristine/adriamycin/dexamethasone) before autologous stem cell transplantation (ASCT). Here we compared the outcomes of the staged approach with frontline PAD (bortezomib/doxorubicin/dexamethasone) or VTD (bortezomib/thalidomide/dexamethasone) induction, and analysed prognostic factors for outcome.Patients and methodsNinety-one transplant-eligible Chinese patients received three induction regimens prior to ASCT [staged approach (N = 25), PAD (N = 31), VTD (N = 35)]. and received thalidomide maintenance for 2 years post-ASCT.Results43 (47.3%) patients had International Staging System (ISS) III disease. By an intention-to-treat analysis, the overall CR/nCR rate were 37.4% post-induction, and 62.6% post-ASCT. Five-year overall (OS) and event-free (EFS) survivals were 66% and 45.1%. There was no difference of the post-induction CR/nCR rate, EFS or OS between patients induced by these three regimens. Moreover, ISS III disease did not affect CR/nCR rates. Multivariate analysis showed that ISS and post-ASCT CR/nCR impacted OS while ISS and post-induction CR/nCR impacted EFS.ConclusionsThese three induction regimens produced comparable and favorable outcomes in myeloma. The unfavorable outcome of ISS stage III persisted despite upfront/early use of bortezomib. CR/nCR predicted favorable survivals.

BK virus-associated bilateral ureteric stenosis after haematopoietic SCT: viral kinetics and successful treatment

BK virus-associated bilateral ureteric stenosis after haematopoietic SCT: viral kinetics and successful treatment

Impact of JAK2V617F mutation on thrombosis and myeloid transformation in essential thrombocythemia: a multivariate analysis by Cox regression in 141 patients.

Abstract Objective: To perform a multivariate analysis by Cox proportional hazard model of the impact of JAK2 V617F mutation on thrombosis and myeloid transformations in patients with essential thrombocythemia (ET). Patients and methods: The clinicopathologic features and outcome of a cohort of Chinese ET patients were retrospectively reviewed. JAK2 V617F mutation was detected by allele-specific polymerase chain reaction. Potential risk factors including JAK2 V617F that might impact on thrombosis and outcome were studied by multivariate analysis with Cox proportional hazard model. Results: Of 141 patients studied, JAK2 V617F was found in 80 cases (57%). JAK2 V617F was positively correlated with hemoglobin and leukocyte count at diagnosis. Univariate analysis showed significant thrombotic risks to be JAK2 V617F (P=0·006), hemoglobin >13 g/dl (P=0·015), and age >55 years (P=0·011). However, in multivariate analysis, only age and hemoglobin were independent risk factors. JAK2 V617F was unrelated to survival or leukemic/myelofibrotic transformation. Conclusion: In Chinese patients with ET, JAK2 V617F was positively associated with age, hemoglobin, and leukocyte count, but was not an independent risk for thrombosis.

Low-dose nivolumab-induced responses in acute lymphoblastic leukaemia relapse after allogeneic haematopoietic stem cell transplantation

Dear Editor, Relapse of acute leukaemia after allogeneic haematopoietic stem cell transplantation (HSCT) has a dismal prognosis, despite the use of chemotherapy, donor lymphocyte infusion (DLI) or second HSCT [1]. For relapses within 1 year postHSCT, current strategies lead to survival in fewer than 10% of cases [1, 2]. Immunotherapy including the use of monoclonal antibodies inotuzumab ozogamicin (anti-CD22) and blinatumomab (anti-CD19) [3], and chimeric antigen receptor T cells [4], is highly effective for relapsed B cell acute lymphoblastic leukaemia (ALL) with or without prior allogeneic HSCT [5–7]. These strategies are limited to leukaemia cells expressing specific B cell antigens and are not applicable to those not expressing these targets. Blockade of the programmed cell death protein 1 (PD1) on effector T cells is a powerful antineoplastic strategy [8]. PD1blocked T cells recognize putative neoantigens and not targets specific to any tumour subtype. Therefore, PD1 blockade is potentially useful in a wide array of malignancies. Its use after allogeneic HSCT, however, is considered a relative contraindication, because of the possible incitement of graft-versushost disease (GVHD). Recently, we tested the hypothesis that PD1 blockade with the antibody nivolumab might exert anti-leukaemic effects in ALL relapsing after allogeneic HSCT, via enhancement of a putative graft-versus-leukaemia (GVL) effect. In order to avoid exacerbating GVHD, a low-dose regimen was used. Patient 1 was a 31-year-old woman presenting in 2013with B cell ALL. Induction chemotherapy with hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, steroid, cytarabine, methotrexate) resulted in first complete remission (CR1). She underwent a matched unrelated donor (MUD)-HSCT. Relapse occurred 10months later, and CR2was achieved withMOAD (methotrexate, vincristine, L-asparaginase, dexamethasone). She then received a second MUD-HSCT from a different donor. Five months later, multiple subcutaneous nodules, renal masses, mediastinal and intra-abdominal lymphadenopathy developed. Biopsy showed extramedullary relapse. Bonemarrow aspirate and trephine biopsies were normal. She was treated with ICE (idarubicin, cytarabine, etoposide) followed by mobilized HSCs from the second donor. Remission could not be achieved, and a biopsy of the left renal lesion 4 months afterwards showed persistence of leukaemia (Fig. 1a). With informed consent, nivolumab was given at the lowest practical dose (40 mg, smallest vial available). No adverse reactions developed, and a second dose of nivolumab (40 mg) was administered 2 weeks later. However, immediately after the second dose, there was a sudden rise in transaminases (Fig. 1b), clinically consistent with hepatitic GVHD [9]. High dose intravenous methylprednisolone (2 mg/kg/day) with mycophenolate mofetil (500 mg twice daily) was started. There was rapid improvement, although transaminases did not return to normal. Positron emission tomography computed tomography (PET/CT) scan 4 weeks after the second dose of nivolumab showed near complete resolution of pre-existing lesions, with residual low-grade metabolic uptake in the renal lesion (Fig. 1a). Owing to ongoing hepatic derangement (Fig. 1c), no further nivolumab was administered. Another PET/CT scan 2 months later showed that the left renal lesion was static in size with increased metabolic uptake (Fig. 1a). Two new cutaneous lesions appeared, which on biopsy showed leukaemic infiltration. Despite radiological evidence * Yok-Lam Kwong ylkwong@hkucc.hku.hk

Favorable response of relapsed/refractory gray-zone lymphoma to brentuximab vedotin

Dear Editor, The two most common lymphomas in the mediastinum are classical Hodgkin lymphoma (cHL) and primary mediastinal large B cell lymphoma (PMBCL) [1]. They present with similar clinic features. Molecularly, PMBCLs are different from other diffuse large B cell lymphomas (DLBCLs) but resemble cHL. Gene expression profiling showed that over one third of genes preferentially expressed in PMBCL, as compared with DLBCLs, were also expressed in cHL [2, 3]. Furthermore, PMBCLs showed low expression levels of multiple components of B cell receptor signaling, which was different from DLBCLs but similar to cHL [3]. A third type of mediastinal lymphoma is gray-zone lymphoma (GZL) [4]. It is diagnosed as B cell lymphoma, unclassifiable, with features intermediate between DLBCL and cHL [5]. Morphologically, GZLs show sheets of lymphoma cells, many of which resemble lacunar cells or Reed-Sternberg cells [6]. Immunophenotypic features are intermediate between cHL and DLBCL, such as uniform staining for CD20, CD15, and CD30. There may be morphologic and immunophenotypic discrepancies, including DLBCL features with a CD20-negative CD15-positive phenotype, or cHL features with a CD20-positive CD15-negative phenotype [6]. GZLs are aggressive, with outcome worse than cHL and PMBCL [7]. CD30 is expressed in cHL, PMBCL, and GZL. The antiCD30 antibody conjugate brentuximab vedotin (BV) is highly effective for relapsed/refractory cHL, inducing an overall response rate (ORR) of 75% (complete response, CR, 34%) [8], and is undergoing evaluation in newly diagnosed diseases [9]. However, BV appears ineffective in relapsed/refractory PMBCL, with an ORR of merely 13.3% (all partial responses, PR) [10]. The efficacy of BV in GZL is not well defined. In a 43-month period (March 1, 2014 to September 31, 2017), we treated 25 cases of hematologic malignancies with BV, of which four cases were GZL. One patient (26-year-old man) was referred with terminal lymphoma and died after the first dose of BV. The response to BV was evaluable in three other patients (Table 1). Patient 1 was a 45-year-old woman presenting in 2014with stage IV DLBCL, who achieved CR after six cycles of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone). She relapsed 1 month later. Excisional biopsy of a supraclavicular lymph node showed features simulating DLBCL. The lymphoma cells were positive for CD30 and CD79a, focally positive for CD15 and BCL6, and negative for CD20. Review of the initial lymph node biopsy showed similar findings, with CD20 only weakly positive. Overall features were consistent with GZL. Positron emission tomography computed tomography (PET/CT) showed widespread dissemination (Fig. 1A). She refused chemotherapy. With informed consent, BV (1.8 mg/kg every 3 weeks) was administered. Serial PET/CT scan showed good response, and all index lesions resolved after the eighth cycle (Fig. 1B), with small foci of minimal metabolic activity present in the liver. The disease progressed after the eleventh cycle. Salvage chemotherapy withDHAP (dexamethasone, cytarabine, cisplatin) was given, followed by autologous hematopoietic stem cell transplantation (HSCT). At the latest follow-up 6 months post HSCT, she has remained in remission. Patient 2 was a 29-year-old woman presenting with a 14cm mediastinal mass invading the pericardium and multiple lymphadenopathy. Cervical lymph node biopsy showed * Yok-Lam Kwong ylkwong@hkucc.hku.hk