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Autologous hematopoietic stem-cell transplantation (ASCT) is one of the most effective therapies for the treatment of multiple myeloma (MM). In this study, we explored factors influencing patients in selecting ASCT by analyzing population-based epidemiological data on patients’ sociodemographic and clinical variables. This multicenter study was conducted across 14 medical centers in Zhejiang Province in China. Patient survey was conducted via face-to-face interviews, telephone interviews, or online completion of questionnaire with patients’ informed consent. Patients were divided into transplantation (TR) and non-transplantation (non-TR) groups. The difference in education levels, occupational status, and annual income between the TR group and non-TR group was significant (P

The heart is a rare primary site of lymphoma, and cardiac involvement is thought to bring a poorer prognosis. A framework of known clinical presentations, diagnostic features, disease complications, treatments, and outcomes to improve prognostication was constructed by a systematic review in 2011. However, some aspects must be discussed further in light of recent advances in lymphoma research. We collected cardiac lymphoma case reports published from January 2009 to January 2019, collected statistics from each patient, and performed a systematic analysis. The epidemiological characteristics, clinical manifestations, treatments, responses, and survival of primary cardiac lymphoma (PCL) patients are described. We obtained 158 cases of heart lymphoma, of which 101 were defined as PCL. There were more male than female cases. Most cases were diffuse large B-cell lymphoma. Six cases of PCL in cardiac myxomas were described. Patients with arrhythmia had shorter progression-free survival compared those without (HR 0.334, 95% CI 0.112-0.999, log-rank P = 0.042). Surgery did not improve patients' long-term prognosis or reduce the risk of death within 1 month. These data suggest that central nervous system prophylaxis is necessary. The overall survival was longer than that in data from 1949 to 2009.

Modulating PD-1 expression can constrain tumor growth. Hodgkin's lymphoma patients commonly express PD-L1 on tumor cells. We report the case of a 60-year-old male patient with relapsed classical Hodgkin's lymphoma who suffered from immediate-onset chill, hyperthermia and polyuria following initial treatment with sintilimab, an anti-PD-1 monoclonal antibody. The results revealed central diabetes insipidus (cDI). After 3 months of treatment with glucocorticoids and desmopressin acetate, his symptoms and the results were consistent with the resolution of cDI and the treatment course was discontinued. Diabetes insipidus is a rare complication of immunotherapeutic treatment, and this is the first case report to our knowledge to have described immediate-onset cDI caused by anti-PD-1 treatment.Lay abstract For relapsed classical Hodgkin's lymphoma, anti-PD-1 monoclonal antibodies have been related to potent safety profiles and efficacy. Reported here is a case of a 60-year-old man diagnosed as having relapsed classical Hodgkin's lymphoma. He achieved a durable response over 4 months with four rounds of traditional chemotherapy, and then the disease relapsed. Sintilimab, an anti-PD-1 monoclonal antibody, was executed for salvage therapy. In spite of the patient-acquired durable response, central diabetes insipidus was detected after the first application of sintilimab. According to our knowledge this is the first case to report immediate-onset central diabetes insipidus caused by the treatment of anti-PD-1. In the present study, we discussed and analyzed the types and clinical causes of diabetes insipidus for this patient.

Chronic mucocutaneous candidiasis (CMC) is a disorder of recurrent or persistent chronic noninvasive symptomatic infections of the skin, nails and mucous membranes. This disorder is primarily caused by Candida albicans. Many factors, including primary immunodeficiencies, can make a host more susceptible to CMC. Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations are the most common genetic etiologies of CMC. We describe a case of CMC with disseminated Talaromyces marneffei infection caused by a new pathogenic Y287N mutation at amino acid 287 in the coiled-coiled domain of STAT1, which was identified using whole-exome sequencing. Position 287 might be a hot spot for missense mutations because several amino acid substitutions were found there. Flow cytometry suggested that the Y287N mutation might reduce the expression of IL-17 of Th17 cells in peripheral blood mononuclear cells stimulated by phorbol myristate acetate and ionomycin. The STAT1 Y287N GOF mutation may be the direct cause of recurrent cutaneous and mucosal candidiasis, including the T. marneffei infection in this patient.

Background: In December 2019, the novel coronavirus pneumonia was detected in Wuhan and named COVID-19. It is an international outbreak of the respiratory illness caused by severe acute respiratory syndrome coronavirus 2. Recent papers pointed out the cytopenia in COVID-19 patients including lymphopenia, neutrophilia, thrombocytopenia and lower level of hemoglobin had prognostic significance. This systemic review and meta-analysis summaries the latest evidence from available data and determine the hematological abnormality caused by severe acute respiratory syndrome coronavirus 2 and potential efficacy on the outcomes in patients with COVID-19. Methods: This protocol for a systematic reviews and meta-analysis will be performed according to the preferred reporting items for systematic reviews and meta-analysis protocols 2015 guidelines. The database of Cochrane Library, PUBMED, EMBASE, Medline, Web of Science, Google Scholar, CNKI, WanFang, as well as gray literatures from the inception to present will be comprehensively and systematically searched without limitations of regions or language. The main study outcomes will be the mortality of COVID-19 patients. The meta-analysis was performed by RevMan V.5.3 program and Stata V.12.0 software after 2 reviewers independently selected literature, data extraction, bias risk evaluation and study quality assessment. Any disagreement will be resolved by consensus to the third researcher. Results: This systematic review and meta-analysis may help provide clarify on the effect of cytopenia in patients with COVID-19. The result will be published at a peer-reviewed journal. Conclusions: This proposed study will evaluate the existing evidence on the effectiveness of cytopenia in COVID-19 patients. Ethic and dissemination: The content of this article does not involve moral approval or ethical review because no individual data will be collected. PROSPERO registration: CRD42020187524.

Epidemiologic studies of the relationship between nitrite or nitrate consumption and risk of non-Hodgkin lymphoma (NHL) remain controversial. The current meta-analysis aimed to reexamine the evidence and quantitatively evaluate that relationship. Manuscripts were retrieved from the Web of Science, Chinese National Knowledge Infrastructure and PubMed databases up to May 2019. From the studies included in the review, results were combined and presented as odds ratios (OR). To conduct a dose-response (DR) analysis, studies presenting risk estimates over a series of categories of exposure were selected. Our data indicate that the consumption of nitrite was linked to a significantly increased hazard of NHL (OR: 1.37; 95% CI: 1.14–1.65), rather than nitrate (OR: 1.02; 95% CI: 0.94–1.10). According to Egger’s and Begg’s tests (P > 0.05), there was no evidence of significant publication bias. Moreover, our DR analysis indicated that the risk of NHL grew by 26% for each additional microgram of nitrite consumed in the diet per day (OR: 1.26; 95% CI: 1.09–1.42). Through subset analysis of the nitrite studies, data from the high-quality studies indicated that consumption was positively associated with carcinogenicity, leading to NHL (OR: 1.44; 95% CI: 1.17–1.77) and positively correlated with the development of diffuse large B-cell lymphoma (OR: 1.55; 95% CI: 1.07–2.26), but not other NHL subtypes. In addition, the data suggested that females (OR: 1.50; 95% CI: 1.15–1.95) and high levels of nitrite intake (OR: 1.64; 95% CI: 1.28–2.09) had a higher risk of NHL. Our meta-analysis supports the hypothesis that nitrite intake, but not that of nitrate, raises the risk of developing NHL. In the future, better designed prospective research studies should be conducted to confirm our findings, clarify potential biological mechanisms and instruct clinicians about NHL prophylaxis.

Acute promyelocytic leukemia (APL) is a rare leukemia characterized by the balanced reciprocal translocation between the promyelocytic leukemia gene on chromosome 15 and the retinoic acid receptor α (RARα) gene on chromosome 17, and accounts for 10-15% of newly diagnosed acute myeloid leukemia each year. The combined use of all-trans retinoic acid and arsenic trioxide (ATO) as primary therapy has markedly improved the survival rate of patients with APL. Mortality in the first 30 days following therapy remains a major contribution to treatment failure. In the present study, published data was reviewed with a focus on the factors associated with early mortality. When treated with ATO as a primary treatment, the fms-like tyrosine kinase-internal tandem deletion has no impact on early mortality. Low lymphoid enhancer binding factor-1 expression may be a reliable marker for early mortality and the target of therapy if it could be proven by further studies. Cluster of differentiation (CD)56+ and CD34+/CD2+ may be candidates to select high-risk patients. The risk of early mortality in APL still cannot be predicted via the cell surface makers, despite multiple studies on their prognostic significance. Typically, a complex translocation did not alter the survival rate in patients with APL; however, if an abnormal karyotype [e.g., Ide(17), ZBTB16/RARα and STAT5B/RARα] appeared singularly or as part of a complex mutation, there is a high possibility of early mortality if clinicians are unable to identify or monitor it.

Objective: To evaluate the efficacy and safety of the combination of haploidentical hematopoietic with low-doseTotal body irradiation（TBI）and cord blood transplantation for hematologic malignancies. Methods: This study was conducted as a retrospective review of medical records of 5 patients with hematologic malignancies who received a combination of haploidentical hematopoietic with low-dose TBI and cord blood transplantation at Affiliated HangZhou first people's hospital of Zhejiang University school of medicine, from March to June 2021. Results: 5 patients were included for the analysis. There were 1 acute myeloid leukemia (AML),2 acute lymphoblastic leukemia (ALL) and 2 Non-Hodgkin's Lymphoma(NHL). The minimal residual disease (MRD) of the two patients with ALL was positive before allo-HCT.Median age of patients at the time of allo-HCT was 30 years (range 21-63 years). All patients received low-dose TBI(4-6GY) +antithymocyte globulin（ATG）based conditioning.Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates. The median values of absolute total nucleated cell counts were 139.0 (80.8-240.0) × 10 7 / kg in The haploidentical grafts and 2.25 (1.32-3.10)× 10 7 / kg in the cord blood units,respectively. The median doses of CD34+ cells infused were 28.6 (22.0-51.1) × 10 5 / kg in the haploidentical grafts and 1.5 (1.0-3.5)×10 5/kg in the cord blood units, respectively.All patients attained complete engraftment,of which 3 were haploidentical engraftment and 2 were mixed hematopoietic chimerism that included haploidentical and cord blood engraftment.The median time to neutrophil engraftment was 12 (10-22) days and 13 (11-22) days for platelets. All patients were in complete remission with MRD-negetive during a median follow-up of 83 (34-136) days.No patients developed grade II-IV acute graft versus host desease. Conclusion:The results suggested that the combination of haploidentical hematopoietic with low-dose TBI and cord blood transplantation may potentially improve the outcome of HSCT. It offers a transplant alternative for patients with hematologic malignancies who lack matching donors. Disclosures No relevant conflicts of interest to declare.

Background Research has demonstrated that histone deacetylase (HDAC) is overexpressed in plasma cells. Panobinostat was the first HDAC inhibitor (HDACi) approved by FDA for the treatment of patients with relapse and refractory multiple myeloma (RRMM) in 2015. Chidamide is an oral subtype-selective HDACi, which was independently developed in China and approved as peripheral T-cell lymphoma. Preclinical findings have demonstrated the anti-myeloma activities of chidamide in vitro and in vivo. Currently, patients are recommended to take bortezomib and/or lenalidomide in first line treatment and might become less sensitive or resistant when disease progressed. Choices are limited for these patients as not all the new agents (i.e., second generation of PIs/ IMiDs, monoclonal antibody, et al.) were covered by insurance in China, which calls for more efficient and economical options. Here we report the initial efficacy and safety of this prospective, phase IIa, multicenter clinical trial with the chidamide based oral quadruplet regimen in patients with RRMM (ChiCTR2000035100). Methods The TC2D regimen (thalidomide 100mg on days 1-28, chidamide 5mg on days 1-24, cyclophosphamide 50mg on days 1-24 and dexamethasone 20mg on days 1,8,15 and 22) was administered to patients with RRMM of a 28-day cycle. In this trial, evaluation of overall response rate (ORR) was based on patients whose response ≥MR and clinical beneficial rate (CBR) was calculated in patients completed at least 3 cycles of TC2D regimen and reached ≥SD in this trial. Results A total of 32 patients were enrolled as of June 30, 2021, with a median age of 63.5 years (range 49-74). iFISH detected high-risk cytogenetics (defined by the presence of del (17p) or p53 mutation, t (4:14), t (14:16), t (14:20), amp (1q)) in 23 patients, and 82% (19/23) of which had unfavorable cytogenetics. All patients were exposed to at least one kind of PIs and/or IMiDs and 75% were double refractory to bortezomib and lenalidomide. 18 patients received 1-3 prior lines and 43% (14/32) were heavily pre-treated (>3 lines). The median number of cycles completed was 3 (range 1-15) and 59% (19/32) patients completed ≥ 3cycles at the cut-off date (Table 1). With the median follow-up of 6 months (range 0.7-19.5), the median progression free survival (PFS) was 3.3 months and the 6-mon PFS rate was 27.5% (Fig1a). Median overall survival (OS) has not reached yet, 6-mon survival rate was 82%, and the estimated 12-month survival rate was 65% (Fig 1b). Study end points were death (8 cases, 25%) and disease progression (24 cases, 75%). Patients who received ≥3 cycles of treatment had a superior median PFS (3.8 vs 1.4 months, P=0.01) than < 3 cycles. Of the 28 patients whose follow-up time more than 3 months, ORR was 25% and CBR was 46.4%, respectively. Better CBR (56.3% vs. 33.3%) and ORR (31.3% vs. 16.7%) were observed in patients who received less than 3 prior lines of therapy, although with no significant statistical difference. Stratified analysis of PFS showed no significant differences in sex, age, clinical classification, cytogenetic risk, prognosis score (DS and ISS staging system), and the status of ASCT. Stratified analysis of OS showed similar results to those associated with PFS. Grade 3/4 adverse events were mainly hematological toxicity (neutropenia 28%, anemia 34%, thrombocytopenia 15.6%), which could be tolerated. Fatigue was reported in 68.8% (22/32) of the patients. The incidence of all-cause infection was 37.5% (12/32). There were no treatment related deaths observed. Conclusions To our knowledge, this is the first report of chidamide-based oral quadruplet regimen for patients with RRMM. The preliminary results suggested excellent efficacy and relatively high safety, and different groups of patients could benefit from treatment with this regimen. A longer treatment period may strengthen this effect. The most common adverse events were hematological toxicity which could be controlled. As we known, choices of treatment are also influenced by physical and emotional impact of hospitalization or frequent hospital visits, which reflects the patient's ability to continue their treatment and quality of life. Hospitalization and intravenous fluids are not involved in this oral quadruplet treatment, which bring far more convenience and could be a cost-effective alternative for patients with RRMM. Updated results will be presented at the following trial. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Mucormycosis is an angioinvasive fungal infection with a high mortality rate. Patients with hematological malignancies following voriconazole therapy are at high risk from mucormycosis. Here, the present study reports on a 68-year-old man diagnosed with multiple myeloma and secondary myelodysplastic syndrome, who was infected with disseminated mucormycosis with cerebellum involvement confirmed by mycological culture and histopathological examination. For patients with hematological malignancies who are receiving antifungal therapy, an opportunistic infection of mucormycosis should be considered if a 'breakthrough' infection occurs in the predilection sites (such as the sinuses, lungs, skin, brain and gastrointestinal tract). It is difficult to diagnose mucormycosis because of the limited reliable detection methods, and because mucormycosis often presents with an acute onset and progresses rapidly, particularly in immunocompromised patients. Antifungal therapy with amphotericin B or posaconazole should be started as soon as possible considering the empirical diagnosis.

Mucormycosis is an angioinvasive fungal infection with a high mortality rate. Patients with hematological malignancies following voriconazole therapy are at high risk from mucormycosis. Here, the present study reports on a 68-year-old man diagnosed with multiple myeloma and secondary myelodysplastic syndrome, who was infected with disseminated mucormycosis with cerebellum involvement confirmed by mycological culture and histopathological examination. For patients with hematological malignancies who are receiving antifungal therapy, an opportunistic infection of mucormycosis should be considered if a ‘breakthrough’ infection occurs in the predilection sites (such as the sinuses, lungs, skin, brain and gastrointestinal tract). It is difficult to diagnose mucormycosis because of the limited reliable detection methods, and because mucormycosis often presents with an acute onset and progresses rapidly, particularly in immunocompromised patients. Antifungal therapy with amphotericin B or posaconazole should be started as soon as possible considering the empirical diagnosis.

Background COVID-19 is an international outbreak of the respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The diseases themselves, as well as the intensity of chemotherapy, lead to significant immunosuppression, leading hematological malignancy patients susceptible to infections. Methods This protocol will be performed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and reported follow the Cochrane Collaboration Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Electronic databases of PubMed, MEDLINE, Google Scholar, Web of science, Cochrane Library, EMBASE, CNKI, CMB, and Wangfang database from the inception to present will be comprehensively and systematically searched without limitations of language, date, and publication status. Observational, retrospective cohort, prospective case-control, cohort studies, cross-sectional studies, or clinical trials will be included. All assessment of study selection, data extraction, and study quality assessment will be independently performed by 2 reviewers. RevMan V.5.3 program and Stata V.12.0 software will be utilized for the methodological quality assessment and statistical analysis. Results The result of this systematic review will provide evidence for clinicians on the management of COVID-19 patients with hematological malignancy. Conclusion This systematic review will help raise awareness and guide management of COVID-19 patients with hematological malignancy, as well as to improve outcomes in this population. Ethic and dissemination The content of this article does not involve moral approval or ethical review because no individual data will be collected. Prospero registration CRD42020187493.

More than half of the patients with acute myeloid leukemia (AML) fail to achieve long-term disease-free survival with current therapies and novel therapeutic strategies are urgently needed. The effects of homoharringtonine (HHT) on the growth of AML cell lines and primary leukemia cells were examined using MTT, colony formation assay. The effects of HHT on both eukaryotic translation initiation factor 4E (eIF4E) and phospho-eIF4E(p-eIF4E) were examined through western blot and immunofluorescence staining. HHT selectively reduced levels of p-eIF4E and its downstream oncoprotein Mcl-1, and potently inhibited in vitro and in vivo the growth of a distinct subset of AML cells and primary leukemia cells expressing high level of p-eIF4E through apoptosis. Our findings suggest that HHT might be a first-in-class p-eIF4E-targeted drug and offer a novel therapeutic option for AML patients expressing high level of p-eIF4E.

The current study presents the case of a 9-year-old Chinese boy who presented with eosinophilia and elevated serum levels of immunoglobulin G4 (IgG4). A bone marrow puncture identified an elevated eosinophil rate of 23% (normal range

This case report describes a 44-year-old female with hepatitis C virus-related thrombocytopenia. The laboratory tests showed a platelet count of 3×109/l, positive HCV serology and high serum concentration of HCV-RNA of 6.74×106 copy/ml. She was refractory to standard therapies including corticosteroids, intravenous immunoglobulin (IVIG), thrombopoietin (TPO) and even interferon (IFN) regimens, due to the persistence of a low platelet count. At first, splenectomy was thought to be impossible, but then splenectomy was successfully performed and patient showed good tolerance and a constant normal platelet count after surgery. In conclusion, splenectomy is feasible in selected patients and may allow us to acquire a reasonable platelet count and completion of an anti-HCV protocol. Low platelet count itself should not be the contraindication of operation specifically for these patients. Further studies in larger numbers of patients and over a longer period of time are warranted.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease disease with 40% of patients presenting as refractory/relapsing disease following R-CHOP treatment. Recently, CD30 was reported as a useful predictor with favorable clinical outcome. However, CD30 expression patterns and the clinicopathologic features of CD30 positive DLBCL are not well described thus far, Here, we studied149 patients with de novo DLBCL to investigate clinicopathologic features of CD30-positive DLBCL by immunohistochemistry. useing a >0% cut-off,CD30 was expressed in approximately 13% (19)patients with DLBCL, showing a lower frequency of MYC/BCL2 co-expression. The clinic features were very similar between the CD30+ and CD30- groups,such as age, sex, B symptoms, staging, ECOG PS, LDH level, extranodal site involvement, IPI, GCB or non GCB type, bone marrow involvement. By univariate analysis Patients with CD30-positive DLBCLs showed better progression-free survival and overall survival compared with patients with CD30-negative DLBCLs, although the superior outcome of CD30 positivity had minimal effects on DLBCL with MYC/BCL2 co-expression. Epstein-Barr virus (EBV) was identified in 8(5.3%) cases, all of which were almost exclusively positive for CD30 expression (8/8) (P < 0·001). We conclude CD30 is expressed in a substantial proportion of DLBCL and CD30 immunohistochemistry may be a useful prognostic marker in R-CHOP treated GCB-DLBCL. The significant association of CD30 with EBV-positive DLBCL suggests a distinct pathobiology for these cases. We concluded that CD30 may be useful as a prognostic marker in rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treated DLBCLs, indicating favorable outcomes Disclosures No relevant conflicts of interest to declare.

Backgroud Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurred non-Hodgkin's lymphoma (NHL). With the development of chemotherapy and immunotherapy, some patients get a good prognosis, but still a considerable number of patients suffer from a strongly aggressive DLBCL with poor treatment effects. Due to the discovery of "double hit" of MYC/Bcl-2 genes, the coexpression of these two proteins has attracted more attention. Further investigations will be necessary to investigate the role of MYC/Bcl-2 co-expression in the clinical features of DLBCL as well as its relationship with prognosisto explore the significance of MYC/Bcl-2 protein coexpression in DLBCL. Methods 89 confirmed DLBCL cases treated with the chemotherapy regimen of CHOP or R-CHOP between February 2008 and March 2014 were collected. Complete clinical data and paraffin-embedded tissues samples were available from these cases. immunohistochemistry analysis of MYC and Bcl-2 protein expression were carried out. In addition, the relationship between MYC/Bcl-2 protein coexpression and factors such as the age, gender, primary site, Ann Arbor staging, international prognostic index (IPI), immunohistochemical Hans type, and Ki-67 expression rate of patients were statistically analyzed in this paper. Furthermore, we investigated how the abovementioned indicators and whether or not Rituximab or MYC/Bcl-2 coexpression was applied were associated with the progression-free survival (PFS) and overall survival (OS) of patients. Results 1. 89 cases with DLBCL were collected. The median age was 65 years with a range of 18-82. 54 cases were over 60 years old. 64 patients had a primary tumor in the lymph nodes .As per the IPI score, there were 30 low-risk cases (IPI 2. 37 cases had high MYC protein expression, accounting for 41.5%. Also, 51cases (57.3%) had high Bcl-2 protein expression. There were 29 cases (32.6%) of MYC/Bcl-2 co-expression Compared with non-coexpression group, the median PFS (16m VS 33m, P 3. Single factor analysis with other common risk factors indicated that in the high-risk group, including advanced aged (grouping by 60 years old)、treating without rituximab III-IV stages, and high IPI score, both PFS and OS decreased, and the difference was statistically significant (P 0.05). 4. In the multivariate regression analysis, It was found that MYC/Bcl-2 coexpression, IPI score, age, and use of rituximab, staging were independent prognostic factors to PFS (P Conclusions Bcl-2/MYC protein coexpression is significantly associated with IPI score of high-risk patients. Patients with MYC/Bcl-2 coexpression had a poorer prognosis than non-coexpression, with shortened PFS. They had a prognosis poorer than single high expressions of MYC or Bcl-2. The influence of MYC/Bcl-2 coexpression to the OS of DLBCL needs a longer follow-up time to study.MYC/Bcl-2 coexpression, IPI score, age, and use of rituximab, staging were independent prognostic factors to prognosis. Disclosures No relevant conflicts of interest to declare.

Thalidomide (Thal), a novel agent in the treatment of multiple myeloma, is presumed to act through a variety of mechanisms. In the present study, we examined the relationship between fibroblast growth factor receptor 3 (FGFR3) expression and the therapeutic effect of Thal. The DNA synthesis of KMS-11 clone, which overexpresses FGFR3, was inhibited by Thal in a dose-dependent manner; whereas U266 cells, which lack FGFR3 expression, failed to respond to Thal inhibition. To further examine the intertwining of Thal's therapeutic effects, wild-type human full-length FGFR3 cDNA was transfected into U266 cells. FGFR3 transfected U266 clones revealed increased FGFR3 expression, but resulted in decreased DNA synthesis and increased apoptosis under Thal treatment. Under Thal treatment, the myeloma proliferation-related protein, vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) were decreased in U266 FGFR3 transfectant as well. These results suggest that Thal inhibits myeloma cell proliferation and may depend on FGFR3 expression status. To further confirm this observation, we transfected a plasmid constructed anti-FGFR3 ribozyme (Rz52) into KMS-11 cells. In the ribozyme transfectant KMS-11 clone, FGFR3 expression was decreased; whereas the effects of Thal in cell growth inhibition were abrogated in KMS-11 Rz52 clone. Further results suggested that Thal inhibition of DNA synthesis, induction of apoptosis, and down-regulation of VEGF and IL-6 might be dependent on FGFR3-associated signal transduction of the ERK and STAT3 phosphorylation pathway. Thus, FGFR3 may be a predictive/surrogate marker for selection of Thal treatment in myeloma.

Cytokine-induced killer (CIK) cells are activated T cells with natural killer (NK) properties that can be expanded in vitro in presence of recombinant human interleukin-2 (rhIL-2) starting from peripheral blood mononuclear cells stimulated by interferon-γ and anti-CD3 antibody. They express CD3 and CD56 as well as the NKG2D antigen and show major histocompatibility complex (MHC)–unrestricted cytotoxicity toward neoplastic but not normal targets. CIK cells express several chemokine receptors, and in vivo models suggest that they can migrate to the site of tumors after intravenous administration, there carrying out their cytotoxic potential and helping to control tumor growth. CIK cells have shown cytotoxic activity in vitro and in vivo against hematopoietic neoplastic cells, including AML (acute myeloid leukemia), CML (chronic myelogenous leukemia), and CLL (chronic lymphocytic leukemia). Their cytotoxicity against patient with B-NHL (B-cell non-Hodgkin lymphoma) , however, has not been fully investigated. The elderly population is susceptible to haematological malignancies, and these elderly patients are intolerant to cytotoxic drugs. Therefore, the exploration of a safe and reliable strategy reduse dose of chemotherapy is critical in improving the prognosis of elderly patients with haematological malignancies. To evaluate the effectiveness and safety of autologous cytokine-induced killer (CIK) cells for consolidation treatmemt in elderly patients with diffuse large B-cell lymphoma. Peripheral blood mononuclear cells (PBMC) were isolated from 20 elderly patients with diffuse large B-cell lymphoma. PBMCs were augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. Autologous CIK cells (range 5 × 10(9)-1 × 10(10)) were then infused back to individual patients. The regimen was repeated every 4 weeks. The host cellular immune function, tumour-related biological parameters, imaging characteristics, disease condition, quality of life and survival time were assessed. Fourteen patients received 6 cycles of transfusion and 6 received 4 cycles. After treatment of CIK cells plus IL-2, the general conditions of 20 patients were to different extent improved No adverse effects were observed. The percentages of CD3(+), CD3(+) CD8(+) and CD3(+) CD56(+) cells were significantly increased (p < 0.05), and the levels of serum β2 microglobulin and lactate dehydrogenase (LDH) were markedly decreased (p < 0.05) after autologous CIK cell transfusion. Cancer-related symptoms were profoundly alleviated, as demonstrated by the improved quality of life (p < 0.01)., Complete remission(CR) observed in 11 patients before the treatmemt of CIK was still CR; Partial remission(PR) in 9 patients ,After the treatmemt of CIK, the transformation of disease state from partial remission to complete remission was seen in 4 patients. At the end of follow-up, the mean survival time was 24 months. Transfusion with autologous CIK cells is safe and effective for treating haematological malignancies in elderly patients. Disclosures No relevant conflicts of interest to declare.

Background. Neutropenic enterocolitis (NE) is a life-threatening complication occurring after intensive chemotherapy; however, only a few data are available for adults with hematological malignancy in China. The aim of this retrospective study was to elucidate the incidence, risk factors, and outcome of NE in adults with hematological malignancy after intensive chemotherapy. Methods. The medical records of 226 adult patients who were diagnosed with hematological malignancy and neutropenic enterocolitis after intensive chemotherapy from 2004 to 2013 were reviewed. Diagnosis of NE was established in case of neutropenic fever, abdominal pain or diarrhea, and bowel wall thickening >4mm on abdominal sonography or CT. Results. Amongst 1804 patients with hematological malignancy treated at the department of hematology, Hangzhou first people's hospital from 2004 to 2013, NE was diagnosed in 226 patients (12.5%), amedian +14(10–19) days after chemotherapy, with a death rate of 11.9%. Bloodstream infections were present in 23 patients, with gram-negative bacteria in 17 patients. Previous therapy with cytarabine and an intestinal wall thickness of ≥10 mm in the ultrasonographic examination affected survival, were associated with greater mortality. In multivariate analysis, the clinical findings of 4 or more symptoms was associated with higher risk of death. Conclusions. NE is a rare but severe complication in patients undergoing intensive chemotherapy. Use of cytarabine, an intestinal wall thickness of ≥10 mm and the clinical findings of 4 or more symptoms were associated with a higher death rate. Disclosures No relevant conflicts of interest to declare.

The aim of this study was to investigate the fibroblast growth factor receptor 3 (FGFR3) mRNA cleavage by ribozymes targeting FGFR3, effect of growth inhibition and associated with mechanism on multiple myeloma (MM). We designated two ribozyme-expressing plasmids that target the FGFR3 genes, Rz52 and Rz32. In vitro catalytic activity of Rz52 and Rz32 in KMS11 cells decreased FGFR3 mRNA expression to 45% (p0.05) and 80% (p0.5), respectively, of that of the control. In vivo examination of the Rz52-transfected KMS11 clone showed that FGFR3 mRNA expression decreased to 20% (p0.05) of the control. In the Rz52-transfected H929 clone, FGFR3 mRNA decreased to 50% of the control. Protein expression of FGFR3 decreased to 70% of the parental KMS11 and H929 clones. DNA synthesis in the Rz52-transfected KMS11 clone decreased to 20% of that of the control, whereas the viability of cells decreased to 2% (p0.01) of that of the control. Ribozyme cleavage-associated increase in apoptosis of Rz52 KMS11 transfectants was twice that of the control. The inhibition of FGFR3 expression by ribozymes was associated with decreased vascular endothelial growth factor (VEGF) expression and upregulation of Flt-1 but not of the KDR receptor. Our data indicate that FGFR3 is an important cell survival and antiapoptotic factor for MM cells and that ribozyme-targeted downregulation of FGFR3 might be useful as a novel therapeutic intervention in MM characterized by t(4;14).

Abstract 3998 The recurrent immunoglobulin translocation, t(4;14)(p16;q32) occurs in 15% of multiple myeloma patients and is the worst prognostic subgroup in MM, although the basis for this poor prognosis is unknown. The t(4;14) is unusual in that it involves 2 potential target genes: fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET). MMSET is universally overexpressed in t(4;14) MM, whereas FGFR3 expression is lost in one-third of cases. Nonetheless, The involvement of MMSET in the pathogenesis of t(4;14) multiple myeloma and the mechanism or genes deregulated by MMSET upregulation are still unclear. Here we demonstrate a role for MMSET in t(4;14) MM cells. We found that Down-regulation of MMSET expression in KMS11 cell by RNA interference and by selective disruption of the translocated MMSET allele using gene targeting dramatically reduced DNA synthesis in KMS11 decreased to 20% of that of the control, whereas the viability of cells decreased to 2% (p_ 0.01) of that of the control and increase in apoptosis was twice that of the control. These findings were associated with reduced expression of genes (e.g. CCND2, CCNG1, MAF and VEGF). These results provide direct evidence that MMSET plays a significant cell survival and antiapoptotic role in t(4;14) MM and suggest that therapies targeting this gene could impact this particular subset of poor-prognosis patients. Disclosures: No relevant conflicts of interest to declare.

Abstract 4838 BACKGROUND: The aim of this study was to determine the safety, tolerance and efficacy of linezolid for the treatment of infections from Gram-positive bacteria in immunocompromised patients with Hematological Malignancy. METHODS: This was a prospective non-comparative unblinded and multi-center study in the Hematology Unit over a one-year period, administering combined use of linezolid in patients with Hematological Malignancy. RESULTS: Fifth-four adult patients received linezolid (600 mg, iv, q12h per day). Thirty-four children received linezolid (30 mg/kgr: 3 i.v. per day).Mean duration of linezolid administration was 12.8 days (range, 10–23days). Among the evaluable patients, fifty four were adults, the median age was 67(range, 30–101years); thirty four were children (range, 11 months-12.6 years), while the median age was 6 years. Primary diagnosis was acute lymphoblastic leukemia (forty-five patients), lymphoma (twenty-three patients), multiple myeloma (eleven patients), Aplastic anemia(four patients), myelodysplasia syndrome(one patients), leucopenia and hemophagocytic syndrome (two patient each). All patients were immunocompromised, 90% of them in the midst of chemotherapy cycles. The mean base number of platelet was 41×109/L(range, 30 – 138×109/L), platelet count less than 30×109/L patients were 28 cases (33%), among them, less than 10×109/L were 13 cases (14.8%). 27 out of 88 patients had positive blood cultures, methicillin-resistant Staphylococcus aureus, eighteen patients; Enterococcus, seven patients; Methicillin Resistant Staphylococcus Epidermidis and hemolytic streptococcus (one patient each).All patients were considered clinically cured after the end of the linezolid regimen (100% efficacy). The main adverse events were thrombocytopenia. There were 11 cases happened transient thrombocytopenia, Among them, four cases were happened within 4 days, seven cases happened four to seven days after received linezolid. Eliminate the possibility caused by reasons such as severe infection which can also result in thrombocytopenia, Linezolid related thrombocytopenia were only two cases (2.3%). Chemotherapy-induced myelotoxicity (90% patients) was not worsened during linezolid therapy. The platelet recovery time was also not lengthened during linezolid therapy. No bleeding episodes were presented, no Self-limited diarrhea were happened. The total adverse event rate was 2.3%; however, there was no premature cessation of linezolid in any patient. CONCLUSIONS: Linezolid may be another effective and safe therapy to treat infections from resistant Gram-positive bacteria in immunocompromised patients, even in children. Disclosures: No relevant conflicts of interest to declare.

Abstract 4723 Chronic disseminated candidiasis (CDC) is typically observed during neutrophil recovery in patients with acute leukemia and requires protracted antifungal therapy. Our objective was to document the efficacy and tolerance of corticosteroid therapy (CST) in patients with symptomatic CDC, including those who experienced fever and abdominal pain despite ongoing antifungal therapy. We performed a study involving 6 adult patients who experienced ongoing symptomatic CDC despite receipt of appropriate antifungal therapy for whom adjuvant oral CST therapy was initiated. All cases of CDC were proven or probable, as determined on the basis of the European Organization for Research and Treatment of Cancer-Mycosis Study Group definition criteria, and occurred in patients with leukemia.The common manifestations in these six patients were persistent fever, splenohepatomegalia and percussion pain in hepatic region. Meanwhile, 2 of them were accompanied with appearance of painful and diffuse cataneous nodules, expectoration and dyspnoea. The abnormal laboratory test observed of them was increase of alkaline phosphatase. Computed tomography scan showed multiple hypodense lesions in the liver and spleen in all the five patients; one of them showed multiple nodular patchy shadows in bone. Nuclear magnetic resonance imaging showed multiple abnormal signal in liver, spleen and kidneys in one of the patients. Three patients had positive blood candida tropicalis cultures. liver biopsy in one patient was negative for fungal. Two patients received Fluconazole therapy empirically, but it was replaced by Itraconazole later in one because of unresponsiveness to the drug. Three patients received Itraconazole therapy and in one received voriconazole therapy empirically. CDC-attributable clinical symptoms resolved with CST, which was started an average of 31 day since antifungal therapy was initiated. Fever and abdominal pain disappeared a median of 5–6 days, and serum fibrinogen and C-reactive protein levels returned to normal values within 14–30 days. Hepatosplenic microabscesses decreased or disappeared within a mean period of 45 days (range, 27–167 days). All the six patients received further chemotherapy smoothly after the treatment antifungal therapy combined with CST,No relapses of CDC were observed during a median duration of follow-up of 3.2 years (range, 2.6–3.8 years).CONCLUSION: In adults who experience persistently symptomatic CDC despite ongoing receipt of antifungal therapy, CST involving a prednisone equivalent at a dosage of > or =0.25 mg/kg per day for at least 3 weeks is associated with a prompt resolution of symptoms and of inflammatory response. These findings support the pathophysiological hypothesis that CDC belongs to the spectrum of fungus-related immune reconstitution inflammatory syndrome. Disclosures: No relevant conflicts of interest to declare.

Abstract 4736 Fusarium is a saprophytic organism that is found widely distributed in soil, subterranean and aerial plants, plant debris and other organic substrates. The organism can cause local tissue infections in immunocompetent patients such as onychomycosis, bone and joint infections, or sinusitis. Since the first case of disseminated Fusarium was described, the incidence of disseminated disease has increased significantly, particularly affecting those immunocompromised with hematological malignancies. We report here a disseminated Fusarium infection with skin manifestations and cerebral aneurysm bleeding in a patient of acute monocytic leukemia. A 49 year old female with acute monocytic leukemia (M5) underwent three courses of therapy with FlAG(cytarabine puls Fludarabine) in second relapse. At the time of hospital admission, she was receiving G-CSF for severe granulocytopenia post-intensification with FLAG, and had also received broad-spectrum antibiotics and fluconazole prophylaxis during previous episodes of febrile neutropenia. Despite treatment with liposomal amphotericin B for five days, She presented persistent fevers, he developed, nonpruritic erythematous Skin Eruption or bleb on her right shin, right shoulder (Figure 1), scalp and foot. The lesions developed central necrosis after four days. The Exudatin in erythematous skin bleb on foot culture was positive for Fusarium solani(Figure 2), which was also confirmed on two different skin lesional drainage culture. Although the patient was treated with liposomal amphotericin B, the clinical symptoms worsened. After liposomal amphotericin B was replaced with voriconazole (VRCZ), Recovery was observed after voriconazole introduction and resolution of neutropenia. Thrombocyte count increased up to 50×109. she suddenly lost consciousness duing lunch. Brain CT scan revealed the hemorrhage in brain. Magnetic Resonance Imaging(MRI) and CTA revealed rupture of brain aneurysm(Figure 3 A,B). Cerebral aneurysm caused by infections differ from congenital brain aneurysm, which often occur the junctions where these arteries come together and form weak spots. The clinical presentation, diagnosis, prognosis and therapeutic options of fusariosis in immunocompromised patients are briefly discussed.Figure 1:Skin EruptionFigure 1:. Skin EruptionFigure 2:The Exudatin in erythematous skin bleb culture was positive for Fusarium solaniFigure 2:. The Exudatin in erythematous skin bleb culture was positive for Fusarium solaniFigure 3:Magnetic Resonance Imaging(MRI) and CTA revealed rupture of brain aneurysm(Figure 3 A,B).Figure 3:. Magnetic Resonance Imaging(MRI) and CTA revealed rupture of brain aneurysm(Figure 3 A,B). Disclosures: No relevant conflicts of interest to declare.

Abstract 4893 The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been shown to improve the outcome in all age groups with newly diagnosed diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis to evaluate the impact on clinical outcomes of adding rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment for diffuse large B-cell lymphoma (DLBCL) patients in china. A propensity score method was used to compensate for the non-randomized study design. From January 2004 to December 2009, 68 patients were newly diagnosed with DLBCL Using Hans' algorithm based on CD10, BCL-6, and MUM1, the non-germinal center (N-GCB) subgroup 45(66.2%) and germinal center B-cell-like (GCB) 23(33.8%). 32 in the rituximab plus CHOP-based chemotherapy (R+) group, and 36 in the CHOP-based chemotherapy only (R-) group. The complete response rate was significantly higher in the R+ group than in the R- group (81.1 vs. 68.1%, P < 0.005,); The complete response rate of N-GCB and GCB in the R+ group was78.2% and 82.1%, p>0.05 respectively. The complete response rate of N-GCB and GCB in the R- group was58.2% and 71.3 %, p P < 0.001. The rituximab can overcome poor outcomes for N-GCB subgroup of DLBCL. The progression-free survival (PFS) at 2 years was 62.4% in the R+ group and 57.0% in the R- group. The 2-year overall survival (OS) was 76.9% for the R+ group and 69.5% for the R- group, P < 0.001. The 2-year overall survival (OS) was 72% in N-GCB Subgroup and 78% in GCB Subgroup for the R+ group, and 48% in N-GCB Subgroup and 68% in GCB Subgroup for the R- group. A multivariate analysis revealed that the addition of rituximab was a strong independent prognostic factor for PFS (hazard ratio 0.64, 95% CI 0.43–0.96, P = 0.031). A subgroup analysis revealed that R+ particularly benefited N-GCB subgroup patients). IPI also showed significant impact for PFS (hazard ratio 1.72, 95% CI 1.34–2.14 for one score increase, P < 0.001 as well as OS P < 0.001. In summary, the addition of rituximab to CHOP-based chemotherapy results in better outcomes for DLBCL patients, particularly patients N-GCB subgroup of DLBCL. Disclosures: No relevant conflicts of interest to declare.

Abstract 4943 The clinical safety of intravenous itraconazole use exceeding 14 days is unknown. However, many cases need further treatment, but the absorption of itraconazole oral in severely ill patients is variable and unpredictable. Gastric acidity and food influence the absorption of oral formulation. The intravenous formulation, on the other hand, achieves adequate blood levels more rapidly and its bioavailability is predictable and invariable compared to the oral formulation. We performed this study to investigate the clinical safety of long-term intravenous itraconazole for the treatment of invasive fungal infection (IFI) in severely ill patients with hematological malignancies. 20 patients (median age, 70 years; range, 38–82 years) with hematological malignancies who had met the IFI inclusion criteria were enrolled. All the infection sites were the lung. These patients were given intravenous itraconazole for 14 days. There were significant effective but the lesions were not fully absorbed and no severe adverse events were found. So the long-term intravenous itraconazole therapy was enabled. Clinical efficacy and adverse events were recorded. Itraconazole 200 mg via intravenous infusion (administered over 1 hour) twice a day for 4 doses followed by 200 mg once a day until the lesions was fully absorbed. The treatment median time was 27(18-58) days. During this period, closely monitor changes in vital signs, chest CT, liver enzymes, renal function, electrocardiogram and electrolytes were assessed. We found that the patients achieved composite endpoints including survival, defervescence and undetectable lesions, except one patient died of primary disease - acute myeloid leukemia. Treatment-related adverse events were found in 7 patients (35%) during the study and none of them were severe adverse events. Such as hypokalemia (10.0%), gastrointestinal disorders (10.0%), elevation of liver enzymes (10.0%) and pleural effusion (5.0%). All the adverse events occurred during the first two weeks of the treatment and no significant exacerbation in the following days. In conclusion, long-term intravenous itraconazole therapy was effective for IFI and the drug-related adverse events have been shown to be generally predictable and manageable. Disclosures: No relevant conflicts of interest to declare.

Abstract 4138 To report a case of All–Trans-Retinoic Acid(ATRA)-induced rhabdomyolysis and acute renal failure in a patient with Acute Promyelocytic Leukemia(APL). A 44-year-old man with underlying APL. Results of the laboratory investigation were as follows: WBC 1.400/dl, hemoglobin 5.7 g/dl and platelets 15000/dl; prothrombin time 15.8 sec, activated partial thromboplastin time 23.4 sec, fibrinogen 75mg/dL (200-590 mg/dL), 3P(+), D-dimer>0.8 mg/dl(0.8 mg/dl( Conclusion,: although ATRA-induced rhabdomyolysis in the induction treatment of APL is a very rare complication, rhabdomyolysis - related ARF carries the risk of high morbidity and mortality. The authors recommended CK monitoring in all patients undergoing ATRA therapy, and withdrawal of ATRA when CK levels exceed 5 times the normal values. Disclosures: No relevant conflicts of interest to declare.

The clinical characteristics and prognosis remain unclear for nasal-type NK/T-cell lymphoma. The aim of this study is to determine the clinical features and outcome. 26 patients diagnosed as nasal-type NK/T cell lymphoma were included in the analysis. Immunophenotype was analyzed by immunohistochemical staining for LCA, CD79α, CD20, CD56, CD3, CD45RO, All the cases of nasal NK/T cell lymphoma were LCA, The positivity rates of CD45RO and CD56 were 89.8%, and 66%, respectively. Tumor cells didn’t express antigens of B and histiocyte, According to Ann Arbor system, 2, 7, 12, and 5 patients had stage I, II, III, and IV. 24 patients received combined chemotherapy(CHOP plus Ara-c) and radiotherapy, and 2 patients received chemotherapy alone. The disease is characterized by predominant young males, a propensity for nodal involvement, frequent stage II–III diseases, low frequency of elevated LDH, low-risk international prognostic index (IPI), high sensitivity to radiotherapy, and intermediate sensitivity to chemotherapy. The 3-year overall survival and progression-free survival for all patients were 88% and 71%, respectively The age, B symptoms, stage, and IPI were important prognostic factors. Combined chemotherapy(CHOP plus Ara-c) and radiotherapy tended to improve the survival for patients with stage and II or III diseases. The distant extranodal dissemination were the primary failure patterns. nasal-type NK/T-cell lymphoma appears to have distinct clinical characteristics and favorable outcomes.

Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (i.e. not yet molecularly defined) myeloproliferative disorder (MPD), along with essential thrombocythemia (ET) and polycythemia vera (PV). All three MPDs represent stem-cell-derived clonal myeloproliferation that, in the case of MMM, is accompanied by an intense bone marrow stromal reaction that includes collagen fibrosis, osteosclerosis, and angiogenesis. To present the results of a long-term analysis of 2 sequential phase 2 trials of thalidomide (alone or in combination) for palliation of myelofibrosis with myeloid metaplasia (MMM). We analyzed (March 2003 to August 2005) initial and long-term outcomes from 33 patients with symptomatic MMM who had enrolled in either our thalidomide single-agent trial (n=12) or our trial of low-dose thalidomide (50 mg/d) combined with prednisone (n=21). Among the 33 study patients, 18 (54%) showed some improvement in their clinical course. Response rates for specific end points included improvements in anemia (12 of 33 [36%]), thrombocytopenia (8 of 12 [66%]), or splenomegaly (5 of 30 [17%]). The combination of low-dose thalidomide and prednisone, as opposed to single-agent thalidomide, was better tolerated and more efficacious. After a median follow-up of 17 months (range, 9–27 months), 10 of 33 patients (33%) showed an ongoing response, including 8 patients in whom protocol treatment has been discontinued for a median of 21 months (range, 16–27 months). Durable treatment responses were documented for only anemia and thrombocytopenia. Treatment response was not affected by the baseline status of bone marrow fibrosis, angiogenesis, osteosclerosis, cytogenetics. Unusual drug effects, all reversible, included leukocytosis (8 patients) and/or thrombocytosis (6 patients). Thalidomide (alone or combined with prednisone) is an effective first-line treatment of symptomatic anemia or thrombocytopenia in MMM. Thalidomide-based therapy has the potential to produce durable responses in MMM-associated cytopenias, even after discontinuation of the drug.

Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus and various partner loci frequently are associated with multiple myeloma (MM). We investigated the expression profiles of the FGFR3/MMSET, CCND1, CCND3, MAF genes, which are involved in t(4;14)(p16.3;q32), t(11;14)(q13;q32), t(6;14)(p21;q32), and t(14;16)(q32;q23), respectively. The analysis was performed by RT-PCR from purified plasma cell populations from 57 MMs and we compared the results with the presence of translocations as assessed by dual-color FISH. A t(4;14) was found in 11MMs, t(11;14) in 9 MMs, t(6;14) in 5 MM, and t(14;16) in 4 MMs. In all cases, the translocations were associated with the spiked expression of target genes. Furthermore, gene expression profiling enabled the identification of putative translocations causing dysregulation of CCND1 (1 MM) and MAF (1 MM) without any apparent involvement of immunoglobulin loci. Notably, all of the translocations were mutually exclusive. IGH-MMSET hybrid transcripts were found in 10 of the 57 (17.7%) MM samples. There was complete concordance between the findings of RT-PCR and FISH analyses of the MM samples, with 19.2% (11/57) t(4; 14) detected by FISH. Samples were separated further into three major groups based on the size of the RT-PCR product. The 1064bp, 438bp, and 275bp of IGH-MMSET were found in 7, 2, and in 1 sample, respectively. We then screened all 57 MM samples for the expression of FGFR3 using RT-PCR, with primers amplifying the 283bp fragments. Specific transcripts were detected in 11 (19.2%) samples that validate the t(4; 14) from cytogenetic studies. In the remaining 46 MM patients without t(4; 14), and 10 normal bone marrow controls, the FGFR3 amplified transcript was barely detectable. Only one patient sample without t(4; 14) revealed detectable levels of FGFR3 expression. Thus, RT-PCR assay for FGFR3 expression can detect all cases with evident or cryptic t(4; 14) translocation (P< 0.01). Using the primers corresponding to 7–10 exon in 11 cases of MM patients with overexpression of FGFR3, we directly sequenced the FGFR3 cDNA fragments amplified by PCR. Polymorphism (GGC>GGT) was detected in nine of the 11 patients. This polymorphism was tightly associated with higher expression of FGFR3. No FGFR3 mutations were found in the remaining 2 MM patients with overexpression of FGFR3. Our data indicate that RT-PCR is a sensitive and reliable method for the detection of FGFR3 and IGH-MMSET. Translocation t(4; 14) in MM detected by FISH can be validated by RT-PCR method. We examined our result by the Chi-Square test and revealed 90% sensitivity and 100% specificity. The Youden Index remains 0.9. This rapid and reliable detection of FGFR3 and IGH-MMSET overexpression may have practical clinical utility in the analysis and monitoring of the disease in MM patients with t(4; 14). Our data suggest the importance of using combined molecular cytogenetic and gene expression approaches to detect genetic aberrations in MM.