Pimjai Niparuck

Treatment outcome of thalidomide based regimens in newly diagnosed and relapsed/refractory non-transplant multiple myeloma patients: a single center experience from Thailand.

BackgroundThalidomide based regimen is an effective and well tolerated therapy in multiple myeloma (MM) patients, however, there were a small number of studies written about the results of thalidomide therapy in non-transplant MM patients. We therefore conducted a retrospective study of 42 consecutive patients with newly diagnosed and relapsed/refractory MM treated with thalidomide- based induction regimens followed by thalidomide maintenance therapy.ResultsInduction regimens with thalidomide and dexamethasone, and the oral combination of melphalan, prednisolone and thalidomide were administrated in 22 and 16 patients, respectively. The remaining 4 patients received other thalidomide- containing regimens. Twenty-nine patients received thalidomide as a salvage regimen. Twenty-three out of 26 patients achieving complete remission (CR) and very good partial remission (VGPR) received thalidomide maintenance. Of the 41 evaluable patients, median time of treatment was 21 months (3- 45 months), ORR was 92.7% with a 63.4% CR/VGPR. With a median follow up of 23 months, 3-year- PFS and 3-year-OS were 58.6 and 72.6%, respectively. Median time to progression was 42 months. While 3-year-PFS and 3-year-OS in non-transplant patients receiving thalidomide maintenance therapy were 67 and 80%, respectively.ConclusionsProlonged thalidomide therapy enhanced survival rate and less frequently developed serious toxicity in non-transplant multiple myeloma patients.

Successful treatment of acquired amegakaryocytic thrombocytopenic purpura refractory to corticosteroids and intravenous immunoglobulin with antithymocyte globulin and cyclosporin

Four patients with acquired amegakaryocytic thrombocytopenic purpura, who had failed corticosteroids, intravenous immunoglobulin and cyclophosphamide therapy, were treated with antithymocyte globulin, followed by cyclosporin. Three patients achieved complete remission in 28–178 days and the response duration was 16–60 months from the beginning of treatment. One patient achieved a partial response for 2 months followed by myelodysplastic syndrome 5 months later. He died in 9 months due to intracerebral bleeding. Marrow cytogenetics showed 47, XY, +21.

Therapy-related myelodysplastic syndrome/acute myeloid leukemia following fludarabine therapy for non-Hodgkin lymphoma and chronic lymphocytic leukemia in Thai patients

Therapy related myelodysplastic syndrome (t-MDS) and secondary acute myeloid leukemia (AML) are seriously late complications of the use of alkylating agents, topoisomerase II inhibitors, and other chemotherapies. Deoxyribonucleic acid (DNA) damage that leads to chromosomal deletions or balanced translocations partly cause t-MDS. Deletions of chromosomes 5 and 7 are also commonly found in alkylator-associated MDS/AML. Over the last half decade, fludarabine has been widely used as frontline therapy for indolent B-cell lymphomas and chronic lymphocytic leukemia (CLL). The incidence of t-MDS/AML following fludarabine-based therapies is 0.5%, 3.5%, 9%, and 2% of patients receiving treatment with fludarabine alone, fludarabine plus chlorambucil, fludarabine combined with cyclophosphamide, and the combination of rituximab, fludarabine, and cyclophosphamide, respectively [1,2]. Nevertheless, the risk factor for fludarabine-induced t-MDS/AML has not been established. We therefore performed a retrospective study to analyze the predicting factors for t-MDS/AML in patients with B-cell lymphomas and CLL treated with fludarabinebased therapy. Thirty-eight patients with B-cell lymphomas and CLL receiving fludarabine-based therapy at Ramathibodi Hospital between January 2003 and December 2008 were included in the analysis. This included all patients with CLL treated with fludarabine at our hospital, with the following exceptions: patients who died within 1 year after fludarabine therapy from non-MDS causes, or patients who received treatment with stem cell transplant, immunoradiotherapy, or a salvage regimen, such as ICE (ifosfamide, carboplatin, etoposide), ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin), IMVP-16 (ifosfamide, methotrexate, etoposide), and hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), were excluded. Thirty-eight patients were treated with fludarabine (F) 30 mg/m/day intravenously (i.v.) for 3 consecutive days, and cyclophosphamide was included for 33 patients receiving the FC regimen. The doses of cyclophosphamide were as follows: cyclophosphamide 600 mg/m/day i.v. on day 1 (nine patients), or cyclophosphamide 200 mg/m/day i.v. for 3 consecutive days (24 patients). Rituximab 500 mg/day

The use of hematocrit level for predicting the efficiency of peripheral blood CD34(+) cell collection after G-CSF Mobilization in Healthy Donors.

Recently, peripheral blood stem cell (PBSC) has been widely used and replaced bone marrow (BM) as the stem cell source in allogeneic hematopoietic stem cell transplantation (HSCT) because of a more rapid engraftment, easier accessibility, and lower risk of donor complications. We, therefore, report the predicting factors for the high PBSC harvest yields in 50 healthy donors. Among the 50 donors, median collected CD34+ cell number was 4.6 × 106/kg (1.5–16.3 × 106/kg). Number of circulating CD34+ cells and hematocrit (HCT) level increased parallelly whereas peripheral CD34+ cell numbers were decreased with increasing donor age. In univariate analysis, HCT level≥ 35.5% at the time of PBSC collection was significantly associated with high PBSC number (≥ 5.0 × 106 cells/kg) and donor aged <30 years was significantly associated with collected CD34+ cells ≥ 6.0 × 106/kg, P = 0.03. HCT level ≥35.5% was an independent parameter for high WBC count (≥50 × 109/L), P < 0.05. None of donor who had both HCT < 35.5% and WBC < 50 × 109/L had circulating CD34+ cells ≥ 5.0 × 106/kg. Platelet count ≥ 200 × 109/L was found significantly in donors with WBC ≥ 40 × 109/L (P = 0.03) and HCT ≥ 35.5%, P < 0.05. Collected PBSC number tended to be higher in our donors with high levels of HCT, WBC, and platelet. We also found that HCT and platelet levels in our donors decreased after receiving G‐CSF administration compared with the initial complete blood counts (CBC) results. We, therefore, concluded that HCT level at the time of initiation leukapheresis was an important predictor for PBSC collection yields. J. Clin. Apheresis 30:329–334, 2015.

Inferior progression-free survival for Thai patients with diffuse large B-cell lymphoma treated under Universal Coverage Scheme: the impact of rituximab inaccessability

The impact of health insurance with inequitable rituximab coverage on the survival of patients with diffuse large B-cell lymphoma (DLBCL) has never been reported. We conducted a nationwide multicenter analysis on the outcome of 553 adult patients consecutively diagnosed with DLBCL between July 2003 and June 2006, in whom treatment cost was reimbursed under the Civil Servant Medical Benefit Scheme (CSMBS) (n =201) or the Universal Coverage Scheme (UCS) (n =352). The international prognostic index was comparable between the two payment groups. Rituximab-based therapy was administered in 45.3% and 3.1% of CSMBS and UCS patients, respectively (p <0.001). With a median follow-up of 24.6 months, the 6-year progression-free survival (PFS) was superior for CSMBS patients (34.2 vs. 23.2%, p =0.005). “Not treated with rituximab-based therapy” was the strongest adverse prognostic feature indicating a short PFS (hazard ratio 2.1, p <0.001). It is concluded that lack of access to rituximab is the principal factor accounting for the inferior PFS observed in Thai patients with DLBCL who are treated under the UCS.

Deferiprone as adjunctive treatment for patients with invasive mucormycosis: A retrospective case series

Mucormycosis is a life-threatening disease requiring multimodal treatment with antifungals and surgery. The mortality rate remains high, prompting consideration of alternative treatment strategies. Deferiprone has in vitro activity against Mucorales, but its efficacy has never been evaluated in humans. Here, we retrospectively analyzed patients with confirmed mucormycosis who received deferiprone from 2011 to 2017. Five patients had hematologic malignancies and one was diabetic. The sites of infection included sinus-orbit-cerebral (67%), lung (17%), and disseminated infection (17%). Surgery was performed in 83% of cases and achieved local control for 33% of patients. A combination regimen of polyenes plus echinocandins was administered with stepdown treatment using posaconazole. The median duration of antifungal treatment was 86 days (range: 46-435 days) days. Deferiprone was given as adjunctive treatment with a median dose and duration of 100 mg/kd/day (range: 86.2-100 mg/kg/day) and 25 days (range: 15-215 days), respectively. Overall, deferiprone was well-tolerated. Successful outcomes were observed at 12-week follow-up for 67% of patients. The mortality rate at 180- day follow-up was 50%. Adjunctive therapy with deferiprone showed safety and tolerability.

Non-Hodgkin lymphoma in South East Asia: An analysis of the histopathology, clinical features, and survival from Thailand

Systemic reports on the descriptive epidemiology of non‐Hodgkin lymphoma (NHL) from Southeast Asia are scarce. A nationwide multi‐institutional registry was conducted to compare the histopathology, clinical features, and survival of Thai adult patients with NHL using large registries, especially those from Far East Asia (FEA). Using a web‐based registry system, 13 major medical centers from the 4 geographic regions of Thailand prospectively collected, from 2007 to 2014, the diagnostic pathology, according to the World Health Organization classification, 2008, clinical features and survival of 4056 patients who were newly diagnosed with NHL. The median age of the patients was 56 years (range, 16‐99 years). The male‐to‐female ratio was 1.3:1. From the total of 4056 patients, T/NK‐cell lymphoma (TNKCL) accounted for 12.6% of cases, and 5.1% had human immunodeficiency virus–associated lymphoma. The four leading histological subtypes were diffuse large B‐cell lymphoma, not otherwise specified (58.1%); follicular lymphoma (5.6%); extranodal mucosa‐associated lymphoid tissue lymphoma (5.2%); and peripheral T‐cell lymphoma, not otherwise specified (4.0%). With a median follow‐up duration of 46.1 months, the median overall survival of B‐cell NHL was significantly longer than that of patients with TNKCL (76.5 vs 28.8 months, P = .0001). Compared to FEA, the Thai registry had an approximately one‐half lower relative frequency of TNKCL; the prevalence of extranodal mucosa‐associated lymphoid tissue lymphoma was much lower than in Korea, and the frequency of extranodal TNKCL, nasal type, was strikingly low compared to China. It is concluded that while the median age of Thai patients with NHL was approximately a decade younger than for Caucasians, the long‐term survival rates for most histological subtypes were comparable. While the histological distribution generally complied with the characteristic Asian features, some differences from FEA were observed.

Improved Survival of Elderly-fit Patients With Acute Myeloid Leukemia Requiring Intensive Therapy: 3-Year Multicenter Analysis From TALWG

Background: Elderly patients with acute myeloid leukemia (AML) have a poorer prognosis than younger ones. Several factors contribute to the poor outcomes for this patient group. Patients and Methods: This study investigated the epidemiology, clinical characteristics, treatment, and clinical outcomes of elderly Thai patients with AML. This 3‐year, prospective, multicenter study was focused on Thai patients with AML aged over 60 years who were diagnosed between 2014 and 2016. Results: Of 680 patients with AML, 235 elderly patients with AML (34.6%) were identified, with a mean age of 70 ± 8 years. Using a 3‐group cytogenetic risk classification (favorable, intermediate, and adverse risk), the proportions of patients in each category were 3.6%, 73.8%, and 22.6%, respectively. The median follow‐up time for surviving patients was 846 days. The median overall survival (OS) of the patients was 128.2 days (range, 0‐1205 days), with a 1‐year OS of 13%. From a multivariate analysis, the significant factors associated with an improved long‐term OS were patients with an Eastern Cooperative Oncology Group performance status 0 to 2 and those receiving intensive therapy. Conclusion: Our study confirms the high prevalence of AML in elderly patients with generally poor outcomes. Selected patients with a good performance status and those who received intensive induction treatment could have a long‐term survival.

Atypical central retinal artery occlusion as the first presentation of POEMS syndrome: a case report

BackgroundPOEMS syndrome is a plasma cell disorder, which clinically manifests from paraneoplastic syndrome: polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. The most common ocular manifestation is optic disc swelling, whereas other ocular manifestations; cystoid macular edema, serous macular detachment, venous sinus thrombosis, infiltrative orbitopathy, uveitis, neovascularization of the disc, peripapillary choroidal neovascularization and optic disc drusen, had also been reported.Case presentationA 52-year-old Thai man presented with 5-day sudden painless visual loss in the left eye. Ocular examination revealed visual acuity of 20/20 and no light perception in the right and left eye, respectively. Right fundoscopic examination was significant for hyperemic generalized optic disc swelling. Left fundoscopic examination revealed opaque and edematous entire retina giving the appearance of central retinal artery occlusion (CRAO) along with pallid “chalky white” optic disc swelling. Fluorescein angiography showed profound leakage of bilateral optic nerve heads and arteriolar filling defect in macular area along with leakage of small retinal arterioles in the left eye. Indocyanine green angiography demonstrated choroidal filling defect in the left eye only. Neuroimaging showed enhancement and luminal narrowing of left internal carotid artery, early subacute watershed infarctions in the left cerebral hemisphere and pachymeningeal enhancement. Cerebrospinal fluid analysis revealed high protein level with normal opening pressure. Intravenous methylprednisolone was initially started without any benefit. After extensive investigations, diagnosis of “POEMS syndrome” was made based on polyneuropathy, elevated lambda light chain level, elevated plasma vascular endothelial growth factor (VEGF), hepatomegaly, spinal sclerotic bone lesions, and thrombocytosis. Furthermore, sural nerve biopsy demonstrated neuropathy and positive VEGF staining. He was treated with eight cycles of bortezomib, cyclophosphamide and dexamethasone (BorCyDex). Polyneuropathy and thrombocytosis had remarkably improved after 2nd cycle, whereas, visual impairment had shown no recovery. Hepatomegaly was significantly reduced after the completion of BorCyDex. Our case eventually received autologous hematopoietic stem cell transplantation with high dose melphalan.ConclusionsTo our knowledge, we illustrated the first patient given CRAO as the first presentation and ocular finding ever reported in POEMS syndrome. Both cerebral and ocular infarctions were presumably the result of VEGF-induced cranial vasculopathy as evidenced by neuroimaging.

The Frequency of SF3B1 Mutations in Thai Patients with Myelodysplastic Syndrome

Genetic mutations in genes encoding critical component of RNA splicing machinery including SF3B1 are frequently identified and recognized as the pathogenesis in the development of myelodysplatic syndrome (MDS). In this study, PCR sequencings specific for SF3B1 exon 13, 14, 15, and 16 were performed to analyse genomic DNA isolated from bone marrow samples of 72 newly diagnosed MDS patients. We found that 10 of 72 (14%) patients harbor SF3B1 missense mutations including E622D (1/72), R625C/G (2/72), H662Q (1/72), K666T (1/72), K700E (4/72) and G740E (1/72), respectively. Mutations were predominantly located on exon 14 and 15 of SF3B1 coding sequence. Interestingly, patients with SF3B1 mutations exhibited higher platelet counts (195×109/L VS. 140×109/L, p-value = 0.025) as well as lower hemoglobin levels (81 g/L VS. 92 g/L, p-value = 0.009) and associated with ring sideroblast phenotype (p-value < 0.001) when compared with patients without the SF3B1 mutation. In summary, we reported the frequency of SF3B1 mutations in Thai patients with different subtypes of MDS. SF3B1 mutations were predominantly occurred in MDS-RS and considered as favourable prognosis value. This study further highlighted the clinical important of SF3B1 mutations analysis for the classification of MDS.