Efficacy Analysis of Bortezomib Combined with Lenalidomide in Newly Diagnosed Multiple Myeloma with 1q21 Gain/Amp.

OBJECTIVE: 1q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in patients with newly diagnosed multiple myeloma (NDMM). To explore the optimal induction treatment, we analyzed and compared the efficacy of combinations of bortezomib-lenalidomide-dexamethasone (VRD) and only bortezomib-based triplet regimens without lenalidomide (only bortezomib-based) as induction therapy in patients with NDMM with 1q21 gain/Amp. METHODS: Seventy-six NDMM patients with 1q21 gain/Amp who were admitted to our center from 2016 to 2022 were retrospectively analyzed in this study. The progression and efficacy of the patients were observed. RESULTS: Within our study group, the overall survival rate stood at 75.0%, and the progression-free survival (PFS) rate reached 40.8% in NDMM patients with 1q21 gain/Amp. The best outcome assessment was that 17.1% achieved complete response (CR) and 44.7% achieved very good partial response (VGPR). Patients in the VRD group had a deeper response (VGPR: 63.6% vs 37.0%, P = 0.034), lower disease progression rate (31.8% vs 70.3%, P = 0.002), longer sustained remission (median 49.7 months vs 18.3 months, P = 0.030), and longer PFS (median 61.9 months vs 22.9 months, P = 0.032) than those treated with only bortezomib-based induction therapy. No significant differences were found among patients with partial response or better (86.4% vs 77.8%, P = 0.532) or CR (27.3% vs 13.0%, P = 0.180). Multivariate analysis showed that only bortezomib-based induction therapy (P = 0.003, HR 0.246, 95% CI 0.097-0.620), International Staging System stage III (P = 0.003, HR 3.844, 95% CI 1.588-9.308) and LMR <3.6 (P = 0.032, HR 0.491, 95% CI 0.257-0.940) were significantly associated with adverse PFS. CONCLUSIONS: When compared with the sequential administration of bortezomib and lenalidomide or only bortezomib-based protocols, NDMM patients with 1q21 gain/Amp may benefit more from VRD as initial treatments.

A novel PEGylated form of granulocyte colony-stimulating factor, mecapegfilgrastim, for peripheral blood stem cell mobilization in patients with hematologic malignancies.

BACKGROUND: The Pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) has longer half-life and is given once only, which is more comfortable for patients. We aimed to evaluate the efficacy of mecapegfilgrastim for hematopoietic stem cell (HSC) mobilization in patients with hematologic malignancies and to explore the potential factors related to HSC mobilization. METHODS: A retrospective analysis was performed on patients who underwent HSC mobilization in the hematology department of Mianyang Central Hospital from April 2016 to November 2022. The number of CD34 + cells collected was compared between the patients receiving mecapegfilgrastim (PEG group) and those receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF group), and the possible factors for mobilization failure were analyzed. RESULTS: The success rates of collecting CD34 + cells in the PEG group and rhG-CSF group were 80.6% and 67.7%, respectively (χ = 1.444, P = 0.229). The median CD34 + cell counts were 3.62 × 10^6/kg and 2.92 × 10^6/kg (P = 0.178), respectively. After combination with plerixafor for mobilization, the median number of CD34 + cells collected in the PEG group and rhG-CSF group were 3.64 × 10^6/kg and 3.92 × 10^6/kg, respectively, with no significant difference (P = 0.754). There was no significant difference in hematopoietic cell recovery or infection between the groups (P > 0.05). Multivariate analysis showed that more than 5 cycles of chemotherapy (OR = 15.897, 95% CI: 1.766-143.127, P = 0.014), a precollection WBC count < 32 × 10^9/L (OR = 14.441, 95% CI: 2.180-95.657, P = 0.006) and a precollection to premobilization lymphocyte ratio < 1.7 (OR = 11.388, 95% CI: 2.129-60.915, P = 0.004) were independent risk factors for HSC mobilization failure. CONCLUSIONS: The HSC mobilization efficacy of mecapegfilgrastim in patients with hematologic malignancies was comparable to that of rhG-CSF, and combination with plerixafor for mobilization was feasible and effective. Patients with more than 5 cycles of chemotherapy before HSC mobilization, a precollection WBC count lower than 32 × 10^9/L, and a precollection lymphocyte count less than 1.7 times the premobilization lymphocyte count have a high probability of HSC mobilization failure.

[Application of Mecapegfilgrastim for Peripheral Blood Hematopoietic Stem Cell Mobilization in Patients With Hematologic Neoplasms and Analysis of Predictors for Poor Mobilization].

Objective: To evaluate the efficacy of applying mecapegfilgrastim for peripheral blood hematopoietic stem cell (PBSC) mobilization in patients with hematologic neoplasms, and to investigate the influencing factors of PBSC collection. Methods: Patients who underwent PBSC mobilization in the Department of Hematology, Mianyang Central Hospital between April 2016 and May 2022 were retrospectively analyzed. The CD34 + cell collection results of two groups, the mecapegfilgrastim group ( n=28), or the PEG group, and the recombinant human granulocyte colony-stimulating factor (rhG-CSF) group ( n=30), were compared, and the influencing factors of collection failure were analyzed. Results: The success rates of CD34 + cells collection in the PEG group and the rhG-CSF group were 75.0% and 63.3%, respectively ( P>0.05). The median CD34 + cell counts were 3.37×10 6/kg and 2.68×10 6/kg, respectively, showing no significant difference. After combined mobilization with plerixafor, the median counts of CD34 + cells collected in the PEG group and rhG-CSF group were 4.23×10 6/kg and 3.26×10 6/kg, respectively, showing no significant difference ( P>0.05). There was no significant difference in hematopoietic system reconstruction and infections between the two groups ( P>0.05). Multivariate analysis found non-plasma cell disease (odds ratio [ OR]=19.697, 95% confidence interval [ CI] : 1.501-258.537, P=0.023), anemia before collection ( OR=18.571, 95% CI: 1.354-254.775, P=0.029) and white blood cell count before collection under 32×10 9 L -1 ( OR=85.903, 95% CI: 4.947-1491.807, P=0.002) to be independent risk factors for PBSC collection failure. Conclusion: The effect of PBSC mobilization with mecapegfilgrastim was comparable to that of rhG-CSF in patients with hematologic neoplasms. Furthermore, combined mobilization with plerixafor was feasible and effective. Patients with leukemia or lymphoma, anemia, and WBC<32×10 9 L -1 before stem cell collection have a high probability of PBSC collection failure.

Effects of peripheral blood leukocyte count and tumor necrosis factor-alpha on early death in acute promyelocytic leukemia.

BACKGROUND: Early death remains a major factor in survival in APL. We aimed to analyze the risk factors for differentiation syndrome and early death in acute promyelocytic leukemia (APL). METHODS: The clinical data of APL patients who were newly diagnosed at Mianyang Central Hospital from January 2013 to January 2022 were retrospectively analyzed. RESULTS: Eighty-six newly diagnosed APL patients (37 males and 49 females) were included in this study. The median age was 46 (17-75) years. Sixty-one patients (70.9%) had low/intermediate-risk APL, and 25 patients (29.1%) had high-risk APL. The incidence of differentiation syndrome (DS) was 62.4%. The multivariate analysis showed that a peak white blood cell (WBC) count ≥16 × 10^9/L was an independent risk factor (OR = 11.000, 95% CI: 2.830-42.756, P = 0.001) for DS in all APL patients, while a WBC count ≥10 × 10^9/L on Day 5 was an independent risk factor for DS in low-intermediate risk APL patients (OR = 9.114, 95% CI: 2.384-34.849, P = 0.001). There were 31 patients (36.5%) with mild DS and 22 patients (25.9%) with severe DS. The multivariate analysis showed that WBC count ≥23 × 10^9/L at chemotherapy was an independent risk factor for severe DS (OR = 10.500, 95% CI: 2.344-47.034, P = 0.002). The rate of early death (ED) was 24.4% (21/86). The multivariate analysis showed that male gender (OR = 7.578,95% CI:1.136-50.551, P = 0.036), HGB < 65 g/L (OR = 16.271,95% CI:2.012-131.594, P = 0.009) and WBC count ≥7 × 10^9/L on Day 3(OR = 23.359,95% CI:1.825-298.959, P = 0.015) were independent risk factors for ED. The WBC count at diagnosis, WBC count on Day 3 and WBC count on Day 5 had moderate positive correlations with tumor necrosis factor-α (TNF-α) at diagnosis, and the correlation coefficients were 0.648 (P = 0.012), 0.615 (P = 0.033), and 0.609 (P = 0.035), respectively. The WBC count had no correlation with IL-6. CONCLUSION: During induction treatment, cytotoxic chemotherapy may need to be initiated to reduce the risk of DS for APL patients with a low-intermediate risk WBC count ≥10 × 10^9/L on Day 5 or for all patients with a peak WBC count ≥16 × 10^9/L. Patients with WBC > 7 × 10^9/L on Day 3 have a higher risk of ED. Leukocyte proliferation is associated with TNF-α rather than IL-6, and TNF-α may be a potential biomarker for predicting ED.

Efficacy and safety analysis of bortezomib-based triplet regimens sequential lenalidomide in newly diagnosed multiple myeloma patients.

The aim of this study is to analyze the efficacy and safety of sequential therapy with bortezomib-based triplet regimens without lenalidomide (PXD, including VTD, PAD, and VCD) followed by continuous lenalidomide and dexamethasone (Rd) or bortezomib and dexamethasone (Vd) treatment. The main objective is to evaluate the advantages of PXD followed by Rd compared to the combinations of bortezomib-lenalidomide-dexamethasone (VRd) in newly diagnosed multiple myeloma (NDMM). Fifty-eight nontransplant NDMM patients who were admitted to our department from 2017 to 2019 were included in this study. Bortezomib-based triplet regimens were initially selected and followed by Rd or Vd as continuous treatment once the patients achieved partial remission (PR) or better response. The efficacy and safety of the patients were observed. The Rd continuous treatment cohort was compared with historical data from the EVOLUTION trial on continuous VRd treatment. In our cohort, the overall survival rate was 100%, and progression-free survival (PFS) was 38.5% after a median of 19 (4-36) cycles of Rd continuous therapy was applied. During the follow-up period, the best outcome assessments achieved were 53.8% complete response (CR) and 84.6% excellent partial response (VGPR). A total of 23.1% had grade 3-4 or higher drug-related adverse reactions, mainly hematological toxicity, and no patients died of adverse reactions. Compared with the Vd group, the Rd group had a better PFS and VGPR rate (2-year PFS: 92.3% vs. 56.3%, P = 0.002; 3-year PFS: 69.2% vs. 8.0%, P < 0.001; VGPR: 84.6% vs. 69.2%, P = 0.02). No significant differences were found in ORR (100% vs. 92.3%) or CR (53.8% vs. 35.7%, P = 0.082). Compared with the EVOLUTION study, patients in the Rd group had a more advanced disease stage (stage III rate of 40% vs. 19%, P = 0.039) and worse physical status (KPS 50-60 rate of 25.0% vs. 2.0%, P = 0.000). However, a higher proportion of ORR (100% vs. 73.0%, P < 0.001), VGPR or better (75.0% vs. 32.0%, P < 0.001), and PFS at 12 months (90.0% vs. 68%, P = 0.011) were achieved. Sequential administration of bortezomib-based triplet regimens without lenalidomide as an initial therapy followed by Rd as a continuous treatment may not be inferior to VRd for first-line treatment in NDMM patients.

Predictors of early death and clinical features in newly diagnosed patients with low-intermediate risk acute promyelocytic leukemia.

Background: Although most acute promyelocytic leukemia(APL) with low-intermediate risk could survive the induction treatment, early death still a big problem to have effects on overall survival in real world.This study aimed to analyze the clinical characteristics and possible predictors of early death in newly diagnosed patients with low-intermediate-risk acute promyelocytic leukemia. Methods: Sixty patients with newly diagnosed low/intermediate-risk APL admitted to Mianyang Central Hospital from January 2013 to December 2021 were retrospectively analyzed. Results: Sixty patients with a median age of 46 years (range, 17-75 years) were included. Fourteen patients (23.3%) were in low-risk group, and 46 patients (76.7%) were in intermediate-risk group. Fourteen patients (23.3%) died during induction treatment. Five patients died of hemorrhage, 5 of severe infection and 4 of differentiation syndrome. Multivariate analysis showed that HGB <65g/L at diagnosis (OR=38.474, 95%CI: 2.648~558.923, P=0.008) during induction treatment was an independent risk factors for early death in low- intermediate risk APL patients. In survival group, all patients achieved complete remission, the time to achieve remission was 25.87 ± 5.02 days, the average ATO dosage was 0.16 ± 0.03 mg/kg/day. In univariate analysis, there was no statistically significant difference in time span for remission when ATO dosage was in the 0.11~0.16mg/kg/day range. Compared with patients with low-risk APL, those with intermediate-risk APL had higher white blood cell counts (at diagnosis, day 3, day 5 and peak), higher level of lactate dehydrogenase, higher percentage of bone marrow promyelocytes, more platelet transfusions during treatment, and more early deaths (P<0.05). The overall survival of intermediate-risk APL patients seemed worse than those with low-risk APL (χ=5.033, P =0.025). Conclusions: In patients with low-intermediate risk APL, HGB <65g/L at diagnosis was an independent risk factors for early death. Remission could still be achieved at low-dose ATO without affecting the required time for low-intermediate risk APL patients. Differences in clinical characteristics were found between low-risk and intermediate-risk APL. The intermediate-risk group had higher early mortality risk than the low-risk group.

Guillain-Barré syndrome and hemophagocytic syndrome heralding the diagnosis of diffuse large B cell lymphoma: A case report.

BACKGROUND: Central nervous system (CNS) lesions and peripheral neuropathy are rare among patients with non-Hodgkin's lymphoma (NHL). Lymphomatous infiltration or local oppression usually accounts for CNS or peripheral nerve lesions. The incidence of peripheral neuropathy was 5%. Guillain-Barré syndrome (GBS) is rare and may occur in less than 0.3% of patients with NHL. Hemophagocytic syndrome (HPS) is a rare complication of NHL. It has been reported that 1% of patients with hematological malignancies develop HPS. Diffuse large B-cell lymphoma (DLBCL) combined with GBS has been reported in 10 cases. CASE SUMMARY: We report the case of a 53-year-old man who was initially hospitalized because of abnormal feelings in the lower limbs and urinary incontinence. He was finally diagnosed with DLBCL combined with GBS and HPS after 16 d, which was earlier than previously reported. Immunoglobulin pulse therapy, dexamethasone, and etoposide were immediately administered. The neurological symptoms did not improve, but cytopenia was relieved. However, GBS-related clinical symptoms were relieved partially after one cycle of rituximab - cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) chemotherapy and disappeared after six cycles of R-CHOP. CONCLUSION: GBS and HPS heralding the diagnosis of Epstein-Barr virus DLBCL are rare. Herein, we report a rare case of DLBCL combined with GBS and HPS, and share our clinical experience. Traditional therapies may be effective if GBS occurs before lymphoma is diagnosed. Rapid diagnosis and treatment of DLBCL are crucial.

Isolated coagulopathy without classic CRAB symptoms as the initial manifestation of multiple myeloma: A case report.

BACKGROUND: Multiple myeloma patients usually present with CRAB symptoms (hypercalcemia, renal disease, anemia and bone diseases) as initial manifestations. Bleeding symptoms are less common, most of which result from thrombocytopenia or infiltration of plasmacytoma. Relatively, coagulopathy is not so common, especially isolated coagulopathy without CRAB manifestations, which is very rare. Herein, we report a 54-year old female who was hospitalized for intermittent and recurrent mild oral mucosal hemorrhage without other bleeding symptoms for almost one month or typical myeloma features. CASE SUMMARY: Two months before admission, the patient underwent implantation of a permanent pacemaker due to sick sinus syndrome. Prothrombin time and activated partial thromboplastin time were significantly prolonged. Factor X deficiency was demonstrated to account for the coagulation dysfunction. An M protein peak was shown by serum protein electrophoresis. 26.11% of abnormal plasma cells were detected in bone marrow by flow cytometry, expressing CD38, CD138, CD56 and intracellular immunoglobulin Kappa light chain. Bone marrow biopsy also proved the presence of abnormal plasma cells, but Congo red stain was negative. The patient was finally diagnosed with multiple myeloma IgA-κ type. A literature review indicated that factor X deficiency was highly related to amyloidosis. Before bleeding signs, the patient had cardiac arrhythmia, enlargement of the heart, and progressive heart failure; thus, cardiac amyloidosis was suspected. CONCLUSION: Bleeding related to coagulation dysfunction is uncommon in multiple myeloma, especially as the initial manifestation. Amyloidosis is a well-recognized cause of isolated acquired factor X deficiency.

A clinical study of peripherally inserted central catheter-related venous thromboembolism in patients with hematological malignancies.

This study aimed to explore the risk factors of peripherally inserted central catheter (PICC)-related venous thromboembolism (CRT) in patients with hematological malignancies and the predictive ability of the thrombotic risk assessment models (RAMs). The clinical data of the 117 eligible patients with hematological neoplasms at Mianyang Central Hospital with PICC from May 2018 to May 2020 were analyzed in this retrospective study. Thrombosis risk scores were calculated in patients with image-confirmed PICC-related thromboembolism. CRT occurred in 19 cases. Compared to the CRT-free group, the CRT group was older and showed higher body mass index (BMI), leukocyte count level, and the prevalence of diabetes mellitus. Multivariable logistic regression analysis showed that BMI (P = 0.03) was a significant risk factor for CRT. The area under the receiver operating characteristic curve for the Caprini scale (P = 0.01) was higher than that of the modified Wells scale (P = 0.94), the revised Geneva scale (P = 0.83), Padua scale (P = 0.59), and Michigan scale (P = 0.80). The sensitivity and specificity for the Caprini scale, Padua scale, modified Wells scale, the revised Geneva scale, and Michigan risk score were 63.3%/73.7%, 100%/0.00%, 95.9%/5.3%, 31.6%/73.7%, and 1.0%/99.0%, respectively. Caprini RAM had a better predictive ability for CRT in patients with hematological malignancies. Michigan risk score may not be better than Caprini RAM in this population.

Dynamic changes and multiplication rate of white blood cell count may direct the timing of cytoreduction chemotherapy during induction treatment in newly diagnosed acute promyelocytic leukemia with low-intermediate risk.

In order to explore the optimal timing for initiating cytoreduction chemotherapy following all-trans retinoic acid plus arsenic trioxide administration, 58 newly diagnosed patients with acute promyelocytic leukemia (APL) with low-intermediate mortality risk were retrospectively analyzed. During induction treatment, white blood cell (WBC) count >4x109/l and multiplication rate of WBC <3 days were defined as rapid WBC multiplication. Patients were divided into two groups: With or without rapid WBC multiplication. Comparison between the two groups revealed that the incidence of differentiation syndrome (DS) (48.1% vs. 6.5%; P<0.001), grade 3-4 bleeding (34.8% vs. 6.5%; P=0.022) and peak WBC count (30.4±20.0x109/l vs. 8.67±5.4x109/l; P<0.001) were significantly higher in the group with rapid WBC multiplication compared with in the group without rapid WBC multiplication. No significant differences were observed in bone marrow depression, infection, complete remission (CR) rate, time to achieve CR and early mortality rate between the two groups. Multivariate analysis revealed that WBC count at chemotherapy initiation was an independent risk factor for the occurrence of DS (P=0.040). Peak WBC count and rapid WBC multiplication were significantly associated with grade 3-4 bleeding (P=0.019 and P=0.002, respectively). Hence, WBC count at chemotherapy initiation along with its multiplication rate may direct the timing of cytoreduction chemotherapy during induction treatment in newly diagnosed APL with low-intermediate risk.

A rare case of acute promyelocytic leukemia with IRF2BP2-RARA fusion; and literature review.

BACKGROUND: Acute promyelocytic leukemia (APL) is commonly characterized by the fusion of retinoic acid receptor alpha (RARA) with promyelocytic leukemia (PML). Most APL patients acquire long-term survival after treatment with all-trans retinoic acid (ATRA) or arsenic agents-based chemotherapy. CASE PRESENTATION: A rare case of APL was reported after IRF2BP2-RARA was detected in the relapsed process using next-generation RNA-sequencing analysis. In addition, the mutation of NRAS was also detected. ATRA and arsenic trioxide combined with daunorubicin were used during induction treatment. The patient acquired complete remission but relapsed in 12 months. The patient was resistant to all other chemotherapies and refused any further therapy. The literature review indicated that allogeneic hematopoietic stem cell transplantation might be a therapeutic method to treat APL with IRF2BP2-RARA fusion. CONCLUSION: Atypical APL should be considered even if the patients present with normal chromosomal karyotype and no classic PML-RARA fusions, but classical clinical features and bone marrow cell morphology. We reported a case of APL with IRF2BP2-RARA fusion was shown to harbor the NRAS mutation at relapse.

The role of renal damage on cardiac remodeling in patients with diabetic nephropathy.

BACKGROUND: Cardiovascular damage and diabetic nephropathy are major complications in patients with Type 2 diabetic nephropathy (T2DN); however, the role of renal damage on cardiac remodeling is not yet fully known. METHODS: A retrospective research was conducted in 254 T2DN patients. All were divided into three groups according to urinary albumin excretion (UAE): the normoalbuminuria group (UAE < 30 mg/g, n = 18), the microalbuminuria group (UAE 30 - 300 mg/g, n = 99) and the macroalbuminuria group (UAE > 300 mg/g, n = 137). The parameters of cardiac remodeling, left atrial diameter (LAD), left ventricular diameter at the end of diastole (LVDd), interventricular septum (IVS), posterior wall of left ventricle (PWLV) and ejection fraction (EF), were determined by Doppler echocardiography. The effects of renal damage on cardiac remodeling were analyzed. RESULTS: Among the 254 patients, LAD and LVDd enlargement was found in 180 (70.86%) and 53 (20.86%) patients, respectively; 46 cases (18.11%) suffered from both LAD and LVDd enlargement. Compared with normal LAD/LVDd groups, creatinine clearance (Ccr) and hemoglobin (Hb) were significantly lower in the left atrial (LA) and left ventricular (LV) dilated groups. LAD was positively correlated with mesangial sclerosis, tubular-interstitial lesions, interstitial fibrosis, as well as tubular basement membrane thickness (r = 0.273, 0.208, 0.176, 0.155, p < 0.05, respectively). Moreover, in comparison to patients with LA enlargement, more severe renal damage was detected in patients with LV enlargement. CONCLUSION: There is a strong correlation between echocardiographic parameters and kidney lesions in patients with T2DN in China; the more severe the renal damage, the more severe the cardiac structural alteration. Renal damage contributes to cardiac remodeling, which may provide new insights into the pathogenesis of cardiovascular complications ,in diabetes mellitus.