Guangzhong Yang

Retrospective analysis of genetic abnormalities and survival in 131 patients with multiple myeloma.

Genetic abnormalities in patients with multiple myeloma (MM) are important risk factors in terms of prognosis. In the present study, the prognostic value of several common MM genetic abnormalities was investigated. Interphase fluorescence in situ hybridization (iFISH) was used to detect genetic abnormalities, including 1q21 gain, t(4;14), t(11;14), t(14;16) and 17p13 deletion in 131 patients. A total of 46.6% patients were detected with one or more abnormalities using iFISH analysis. The 1q21 gain, t(4;14), t(11;14), t(14;16) and 17p13 deletion abnormalities were detected in 42.5, 6.9, 17.5, 0.8 and 10.7% of patients, respectively. Patients with t(4;14) commonly exhibited lower levels of albumin and hemoglobin. The progression-free survival (PFS) and overall survival times of iFISH-positive patients (particularly patients with two or more iFISH abnormalities) were significantly shorter than those of the patients without detectable abnormalities. The 1q21 gain and 17p13 deletion were also adverse prognostic factors for MM. Bortezomib-based therapies improved the PFS times in the patients with unfavorable iFISH abnormalities. These findings demonstrate that patients with two or more iFISH abnormalities, a gain of the 1q21 region or a 17p13 deletion were more likely to have a poor prognosis; however, bortezomib treatment improved the outcome for MM patients with unfavorable iFISH abnormalities.

Primary mediastinal myelolipoma: A case report and review of the literature

Myelolipoma is a rare, benign neoplasm composed of mature adipocytes and hematopoietic tissue, mainly occurring in the adrenal glands. The majority of extra-adrenal myelolipomas have been identified in the presacral region and primary mediastinal myelolipoma is very rare. Computed tomography (CT) and magnetic resonance imaging (MRI) are effective methods to detect myelolipoma, while fine-needle aspiration (FNA) combined pathology is able to definitively rule out malignancy. There is no standard method of treatment for the disease. Small (<4 cm) asymptomatic tumors should be monitored, while symptomatic tumors or large (>7 cm) myelolipomas should be removed by surgery. This study describes a patient who presented with two mediastinal myelolipomas that were not encapsulated and presented as a string-of-pearls-type. The pathological diagnosis was myelolipoma and the patient did not relapse within the three years following resection.

Significance of oligoclonal bands after stem cell transplantation in multiple myeloma cases.

OBJECTIVE To determine the characteristics of oligoclonal bands that are frequently detected by serum protein electrophoresis (SPEP) and immunofixation electrophoresis (IFE) after stem cell transplantation. METHODS We retrospectively analyzed 56 patients with multiple myeloma (MM) undergoing transplantation, and standard immunofixation electrophoresis was used to identify and quantify paraproteins. RESULTS The median follow-up was 35 months (range, 10-76 months) and 21 patients relapsed. Twelve (25.0%) demonstrated oligoclonal bands after a median time 1.4 months (range, 1-3 months), with a median duration of 5.8 months (range, 1-15 months). The majority patients with oligoclonal bands had normal quantities of immunoglobulins and the one year event free survival (EFS) was 92%, even higher than for patients without OBs (P=0.002). CONCLUSION Oligoclonal bands frequent develop post-transplantation in MM cases. In the vast majority of patients, they may not represent relapsed disease, and more likely represent a transient phenomenon representing recovery of impaired immunoglobulin production.

Toll-Like Receptor 4 Is Required for the Cytotoxicity of Cytokine-Induced Killer Cells

Cytokine-induced killer (CIK) cells are heterogeneous effector T cells with diverse T-cell receptor specificities with non-major histocompatibility complex-restricted cytolytic activities against tumor cells and are considered a promising therapeutic approach against hematologic malignancy. Recently, it has been reported that IL-15-activated CIK cells are superior to cells generated according to the standard protocol; however, the underlying mechanism remains to be elucidated. In the present study, we found that in IL-15-stimulated CIK cells, Toll-like receptor 4 (TLR4) expression was upregulated. Upon knockdown of TLR4, the cytolytic activity was considerably compromised. Re-expression of TLR4 in CIK cells restored their function, confirming the essential role of TLR4 in CIK cell cytotoxicity. Collectively, our study demonstrated that TLR4 was essential for the cytotoxicity of CIK cells against tumor cells, which might provide a novel approach to promote the therapeutic efficacy of CIK cells against hematologic malignancy.

Retrospective analysis of 264 multiple myeloma patients

Multiple myeloma (MM) is the second most common hematological malignancy in China. However, there are only a small number of large cohort studies demonstrating the clinical features of newly diagnosed MM. In the present study, 264 newly diagnosed MM patients from the Beijing Chaoyang Hospital were retrospectively analyzed. The median patient age was 59 years (range, 28–84) and the most common monoclonal protein (42%) was the IgG subtype. Of the 49 patients detected by FISH, 10.2, 2.0 and 12.2% demonstrated del(17p), t(14;16) and t(4;14), respectively. In total, 228 (86%) patients achieved either a complete response (CR), a very good partial response (VGPR) or a partial response (PR). The overall response rate (ORR) in non-autologous stem cell transplantation (non-ASCT) patients was 83.0%, with 48 (18.2%), 7 (2.7%) and 121 (45.8%) patients achieving CR, VGPR and PR, respectively. ASCT patients achieved at least a PR prior to ASCT, and ASCT was not able to increase the ORR (P=0.55). Non-ASCT patients who received bortezomib-based regimens demonstrated an improved ORR compared with those who received regimens that did not contain bortezomib (92.3% vs. 75.8%; P<0.05). With a median follow-up time of 20 months, the estimated median progression-free survival (PFS) and overall survival (OS) times were 27.6 and 61.0 months, respectively. The OS time of patients with high-risk cytogenetic abnormality, del(17p), t(14;16) and t(4;14), was shorter compared with that of other patients (30.2 months vs. not reached, P=0.029). Patients who achieved a CR/VGPR in the ASCT group demonstrated a greater OS time compared with non-ASCT patients (P=0.031). Relapsed patients who received bortezomib-based regimens did not demonstrate a longer survival time post-relapse compared with those who received non-bortezomib-based regimens (26.5 months vs. 10.5 months; P=0.271). The current study presented the clinical characteristics of MM patients who were initially treated at the Beijing Chaoyang Hospital. Bortezomib-based regimens and ASCT were able to improve the OS of MM patients.

Bortezomib, dexamethasone plus thalidomide for treatment of newly diagnosed multiple myeloma patients with or without renal impairment

OBJECTIVE To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) with or without renal impairment receiving the therapy of bortezomib, dexamethasone plus thalidomide (BTD) regimen in order to analyze the effects of BTD regimen on the prognosis of the MM patients with renal impairment compared with the patients without renal impairment. METHODS Seventy-two newly diagnosed MM patients entered into our study and all the patients belonged to International Stage System (ISS) 3 in which transplantation patients were excluded or the patients refused receiving transplantation therapy. According to the level of serum creatinine (Scr), the patients were divided into two groups including group 1 (n=42) (Scr <2 mg/dL) and group 2 (n=30) (Scr ≥2 mg/dL). All the patients received the therapy of BTD regimen as induction therapy, and the median treatment time was 5 (range, 2-8) cycles. The outcome was analyzed retrospectively. RESULTS The overall remission (OR) rates were 81.0% (group 1) and 80.0% (group 2). There was no statistical difference between the two groups (P>0.05). In group 2, 10 patients (33.3%) got renal function reversal, 14 patients (46.7%) got improved renal function and the median time to renal function reversal was 1.4 (range, 0.7-3.0) months. Among 12 patients with hemodialysis at diagnosis, 8 patients got rid of hemodialysis after median 4 cycles of therapy (range, 3-6 cycles). After a median follow-up period of 16 (range, 2-31) months, 5 patients (11.9%) in group 1 died and 9 patients (30.0%) in group 2 died (P=0.056). The 2-year estimate of overall survival was 77.3% in group 1 and 63.8% in group 2, respectively (P=0.188). During a median follow-up time of 13.0 months (range, 2-25 months), 15 patients (35.7%) in group 1 progressed and 13 patients (43.3%) in group 2 progressed (P=0.513). The 2-year estimate of response duration was 50.6% in group 1 and 42.1% in group 2, respectively (P=1). The main toxicities in the two groups included thrombocytopenia, peripheral neuropathy (PN), infection, herpes zoster and so on. The incidence of grade 3 and 4 adverse events was low. CONCLUSIONS BTD regimen may become the front-line therapy for the newly diagnosed MM patients with renal impairment because BTD regimen can improve the prognosis of the patients with renal impairment as good as the patients without renal impairment.

Management of Tumor Lysis Syndrome in Patients With Multiple Myeloma During Bortezomib Treatment

BACKGROUND Tumor lysis syndrome (TLS) is a severe, life-threatening complication that typically occurs in highly proliferative malignancies. Although TLS is unusual in multiple myeloma (MM), it is still associated with significant morbidity. Bortezomib has been widely used for the treatment of MM with encouraging results, but TLS seems to occur more frequently in patients with MM receiving bortezomib than in patients receiving other conventional agents. OBJECTIVES The purpose of this article is to present and examine several significant risk factors for the development of TLS, based on the results of a study involving patients with MM who developed TLS during bortezomib treatment. METHODS Patients with MM were treated with bortezomib-containing regimens. FINDINGS The early identification and intervention of high-risk patients with MM is imperative. Timely and efficient management could decrease TLS incidence rates and improve the efficacy of treatment outcomes.

Autoantibodies against β1-adrenergic receptor: response to induction therapy with bortezomib-containing regimens for multiple myeloma patients

Abstract This study aims to investigate the predictive value of pre-chemotherapy β1R-AABs by evaluating the response of newly diagnosed symptomatic multiple myeloma (MM) patients to their treatment with a bortezomib-containing regimen. Forty-five de novo MM patients and 50 normal controls (NCs) were prospectively enrolled in this study. Serum titers of β1R-AABs were detected by ELISA. These 45 MM patients were divided into two groups (positive and negative groups) according to their β1R-AABs. Follow-up examinations were performed on these patients during chemotherapy induction. The final analysis covered all 45 MM patients, including 19 patients who were positive for MM and 26 patients who were negative for MM. Multivariate analysis revealed that pre-chemotherapy β1R-AABs are possibly independent predictors for less than very good partial response (VGPR) after the bortezomib-containing regimen treatment (odds ratio: 5.967, 95% confidence interval: 1.513–23.531; p = .011). This study demonstrates for the first time that the presence of β1R-AABs is associated with MM. Pre-chemotherapy β1R-AABs are independent predictors for less than VGPR in de novo MM patients after the bortezomib-containing regimen was administrated. Bortezomib might not significantly give rise to cardiac impairment in MM patients.

A Report of 134 Newly Diagnosed Multiple Myeloma Patients with Renal Impairment

To analyze the effects of bortezomib on the prognosis of the newly diagnosed multiple myeloma patients with renal impairment, we assessed the outcomes of 134 multiple myeloma patients with renal impairment (serum creatinine ≥178 μmol/l) who were treated at Beijing Chaoyang Hospital. The patients were divided into two groups: bortezomib (n = 83) and nonbortezomib (n = 51). The overall response rate of the bortezomib group was higher than that of the nonbortezomib group. There was no significant difference in the time to restore renal function, but the complete renal response ratio was significantly higher in the bortezomib group. The 2-year overall survival (OS) rate of the bortezomib group was significantly greater than the nonbortezomib group, as was the 3-year OS rate. Kaplan-Meier analysis revealed significantly better survival for the bortezomib group. The main side effects in the bortezomib group were thrombocytopenia, peripheral neuropathy, infection, and herpes zoster, and there was a low incidence of grades 3 and 4 adverse events. Our findings indicate that bortezomib-based combination chemotherapy can improve the prognosis of the newly diagnosed multiple myeloma patients with renal impairment and should be considered as a first-line therapy.

Target and resistance related proteins of recombinate mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) on myeloma cell lines

Recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) has become a potential therapeutic drug for multiple myeloma (MM). However, the exact targets and resistance mechanisms of rmhTRAIL on MM cells remain to be eluci- dated. The present study aimed to investigate the target and resistance-related proteins of rmhTRAIL on myeloma cell lines. A TRAIL-sensitive myeloma cell line, RPMI 8226, and a TRAIL-resistance one, U266, were chosen and the differ- entially expressed proteins between the two cell lines were analyzed prior and subsequent to rmhTRAIL administration by a liquid chromatography-tandem mass spectrometry method. The results showed that following TRAIL treatment, 6 apoptosis-related proteins, calpain small subunit 1 (CPNS1), peflin (PEF1), B‑cell receptor‑associated protein 31 (BAP31), apoptosis-associated speck-like protein containing CARD (ASC), BAG family molecular chaperone regulator 2 (BAG2) and chromobox protein homolog 3 (CBX3), were upregulated in RPMI 8226 cells while no change was identified in the U266 cells. Furthermore, small ubiquitin‑related modifier 1 and several other ubiquitin proteasome pathway (UPP)-related proteins expressed higher levels in TRAIL-resistant cells U266 compared to the RPMI-8226 cells prior and subse- quent to rmhTRAIL treatment. These results suggested that CPNS1, PEF1, BAP31, ASC, BAG2 and CBX3 were possibly target proteins of rmhTRAIL on RPMI 8226 cells, while UPP may have a vital role in mediating TRAIL-resistance in U266 cells.