Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of αβ or γδ type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 γδ enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) β,γ and, in cases tested, δ negative (presumptive NK origin); 5% were TCR γδ, 3% were TCR αβ, 1% were TCR αβ/γδ, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only αβ T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with γδ EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ≥2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal γδ EATL.
BackgroundCytogenetic abnormalities and mutated genes indicate the role of consolidation therapy with hematopoietic stem cell transplantation (HSCT) or chemotherapy in acute myeloid leukemia (AML). In this study, we conducted a retrospective study in adult AML patients with newly diagnosed with de novo AML who did not undergo HSCT, to study long term relapse free survival (RFS) and overall survival (OS) after consolidation chemotherapy.MethodsWe recruited 141 consecutive AML patients during January 2010–June 2017, the patients received induction chemotherapy with standard dose Ara-C and Idarubicin (7 + 3 or 5 + 2 regimen) followed by intermediate (IDAC) or high dose Ara-c (HiDAC) consolidation therapy.ResultsNormal karyotype, complex, favorable, intermediate and adverse chromosomal aberrations were found in 59%, 16%, 5%, 14% and 6%, respectively. Mutated NPM1, FLT3-ITD and CEBPA genes in CN-AML were seen in 33%, 18% and 19%, respectively. A 5 year follow up, 5y-RFS was 16% and 5y-OS was 14% in the whole study population. 5y-RFS and 5y-OS in patients completed 4 cycles of consolidation therapy were 25% and 40%, respectively. Adverse cytogenetic risk and mutated FLT3-ITD were significantly associated with poor RFS (9 and 15 months, respectively) and OS (14 and 16 months, respectively), whereas patients with mutant NPM1 had favorable outcomes (RFS/OS = 51/63 months). Patients receiving 4 cycles of consolidation therapy had significantly impacts on median RFS and OS compared with those treated with 1 or 2 cycles; 15 versus 11 months (p = 0.006) and 31 versus 15 months (p < 0.001), respectively.ConclusionsCytogenetic and mutation tests for FLT3-ITD, NPM1 and CEBPA genes were meaningful for predicting outcomes in adult AML patients. Adverse cytogenetic abnormalities and FLT3-ITD mutation showed dismal RFS and OS.
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.
Objectives Standard treatment with a thiotepa-based regimen in countries with a limited resource is less feasible. Aims of the study were to evaluate the treatment outcome, and identify the prognostic factors in patients with primary central nervous system lymphoma (PCNSL). Methods We conducted a retrospective study of 43 patients diagnosed with PCNSL, DLBCL subtype, who were treated with either HDMTX-based regimen, whole brain radiotherapy (WBRT), or both between 2010 and 2017. Results There were 43 patients with a median age of 65 years (range 34–89 years). Protein expression of CD10, Bcl6, MUM1, Bcl2 and MYC were found in 19, 86, 91, 91 and 23%, respectively. Both germinal center B cell (GCB) and double-expressor (MYC+/Bcl2+) lymphomas were found in 21%. Multiple brain lesions and maximum tumor diameter (MTD) ≥5 cm were seen in 27 and 10 patients, respectively. Chemotherapy combined with WBRT, chemotherapy and WBRT were given to 20, 14 and 9 patients, respectively. Overall complete remission (CR) rate was 55.8%. Those receiving a combined-modality therapy had a higher CR rate than those treated with either chemotherapy (75% versus 36%, p = 0.036) or WBRT (75% versus 44%, p = 0.109). Median follow-up time was 17 months, and a 7-year overall survival (OS) was 40%. Features associated with a prolonged OS were an ECOG score ≤ 2 ( p = 0.001), multiple brain lesions ( p = 0.010), multiple area of brain involvement ( p = 0.023), MTD < 5 cm ( p = 0.004), GCB subtype ( p = 0.003) and positive CD10 staining ( p = 0.007). Expression of Bcl2 protein was associated with a significantly worse OS in the non-GCB DLBCL patients. Discussion The factors affecting treatment outcomes in PCNSL were cell of origin of DLBCL, lesion characteristics, patients’ status and treatment regimen.
Persistent immune thrombocytopenia (ITP) patients require second-line treatments, for which information on clinical outcomes are lacking. A systematic review and network meta-analysis (NMA) were conducted. Only randomised controlled trials (RCT) of second-line drugs in adult persistent ITP patients with platelet response, platelet count, any bleeding or serious adverse events (SAE) outcome were eligible. Twelve RCTs (n = 1313) were included in NMA. For platelet response outcome, eltrombopag and romiplostin were the best relative to placebo; the former had a non-significant advantage [risk ratio (RR) = 1Á10 (95% confidence interval: 0Á46, 2Á67)]. Both treatments were superior to rituximab and recombinant human thrombopoietin (rhTPO)+rituximab, with corresponding RRs of 4Á56 (1Á89, 10Á96) and 4Á18 (1Á21, 14Á49) for eltrombopag; 4Á13 (1Á56, 10Á94) and 3Á79 (1Á02, 14Á09) for romiplostim. For platelet count, romiplostim ranked highest, followed by eltrombopag, rhTPO+rituximab, and rituximab. For bleeding, rituximab had lowest risk, followed by eltrombopag and romiplostim. For SAEs, rhTPO+rituximab had highest risk, followed by rituximab, eltrombopag and romiplostim. From clustered ranking, romiplostim had the best balance between short-term efficacy and SAEs, followed by eltrombopag. In conclusion, romiplostim and eltrombopag may yield high efficacy and safety. Rituximab may not be beneficial due to lower efficacy and higher complications compared with the thrombopoietin receptor agonists. RCTs with long-term clinical outcomes are required.
Introduction Vaccine‐induced thrombotic thrombocytopenia (VITT) has been reported after vaccination with the adenoviral vector coronavirus disease 2019 (COVID‐19) vaccine ChAdOx1 nCoV‐19 in European countries. To date, two cases of VITT have been reported in Thais after COVID‐19 vaccination. We determined the frequency of anti–platelet factor 4 (PF4)/polyanionic antibodies in the Thai population receiving the COVID‐19 vaccines. Methods We conducted a cross‐sectional study to evaluate the prevalence of anti‐PF4/polyanionic antibodies in health care workers who received COVID‐19 vaccination with ChAdOx1 nCoV‐19 or CoronaVac within 7 to 35 days. A control population who had not been vaccinated was also included. Anti‐PF4/polyanionic antibodies were detected using ELISA. Functional assay with platelet aggregation was performed for all positive anti‐PF4/polyanionic antibody ELISA tests. Results A total of 646 participants were included in the study; 221 received ChAdOx1 nCoV‐19, 232 received CoronaVac, and 193 participants were in the control group. The prevalence of anti‐PF4 antibodies was 2.3% (95% confidence interval [CI], 0.7‐5.2), 1.7% (95% CI, 0.5‐4.4) in the ChAdOx1 nCoV‐19 and CoronaVac groups, respectively. There was no positive test in the control group. None of the PF4/polyanionic positive sera induced platelet aggregation. Conclusion We found a low prevalence of anti‐PF4 antibodies in Thais after vaccination with ChAdOx1 nCoV‐19 and CoronaVac. None of the antibodies were functional and lacked an association with VITT.
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 × 10(6/) kg (1.5-16.3 × 10(6) /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 × 10(6) cells/kg) and donor aged <30 years was significantly associated with collected CD34+ cells ≥ 6.0 × 10(6) /kg, P = 0.03. HCT level ≥35.5% was an independent parameter for high WBC count (≥50 × 10(9) /L), P < 0.05. None of donor who had both HCT < 35.5% and WBC < 50 × 10(9) /L had circulating CD34+ cells ≥ 5.0 × 10(6) /kg. Platelet count ≥ 200 × 10(9) /L was found significantly in donors with WBC ≥ 40 × 10(9) /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.
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