The significance of autologous hematopoietic stem cell transplantation on immunoglobulin reconstitution and prognosis in elderly patients with multiple myeloma.

OBJECTIVES: Autologous hematopoietic stem cell transplantation (ASCT) is a crucial method used in patients with multiple myeloma (MM). This study aims to evaluate the role of ASCT in immunoglobulin (Ig) reconstitution and long-term outcomes in patients aged ≥ 60 years. METHODS: From March 2008 to May 2019, 93 patients aged ≥ 60 years who were diagnosed with MM and underwent ASCT were retrospectively analyzed. All patients underwent follow-ups and the deadline for follow-up was October 31, 2022. The Ig levels were measured using the immune turbidimetry method at 3, 6, and 12 months after transplantation. Patients who died or experienced relapse were excluded from the analysis. The prognostic value of Ig levels was estimated using the Kaplan-Meier survival curve and Cox regression method. RESULTS: No patients died, and all patients with complications showed improvements after treatment. Patients in the Ig reconstitution group had a lower international staging system (ISS) stage, whereas those in the immunoparesis group had a higher ISS stage. The median duration of follow-up was 36 (range, 13-120) months. The Ig reconstitution within 12 months indicated a longer overall survival and progression-free survival outcomes. The detection of Ig levels was an independent indicator for the prognosis of MM. DISCUSSION AND CONCLUSION: The Ig reconstitution within 12 months of ASCT could predict the overall outcomes of patients with MM aged ≥ 60 years.

Dynamic assessment of measurable residual disease in favorable-risk acute myeloid leukemia in first remission, treatment, and outcomes.

We aimed to investigate outcomes of different post-remission treatment (PRT) choices based on dynamic measurable residual disease (MRD) by multiparameter flow cytometry in favorable-risk AML (FR-AML). Four hundred and three younger patients with FR-AML in first complete remission (CR1) were enrolled in this registry-based cohort study, including 173 who received chemotherapy (CMT), 92 autologous stem cell transplantation (auto-SCT), and 138 allogeneic SCT (allo-SCT). The primary endpoint was the 5-year overall survival (OS). Subgroup analyses were performed based on dynamic MRD after the 1st, 2nd, and 3rd courses of chemotherapy. In subgroups of patients with negative MRD after 1 or 2 course of chemotherapy, comparable OS was observed among the CMT, auto-SCT, and allo-SCT groups (p = 0.340; p = 0.627, respectively). But CMT and auto-SCT had better graft-versus-host-disease-free, relapse-free survival (GRFS) than allo-SCT in both subgroups. For patients with negative MRD after three courses of chemotherapy, allo-SCT had better disease-free-survival than CMT (p = 0.009). However, OS was comparable among the three groups (p = 0.656). For patients with persistently positive MRD after 3 courses of chemotherapy or recurrent MRD, allo-SCT had better OS than CMT and auto-SCT (p = 0.011; p = 0.029, respectively). Dynamic MRD might improve therapy stratification and optimize PRT selection for FR-AML in CR1.

Association Between Measurable Residual Disease in Patients With Intermediate-Risk Acute Myeloid Leukemia and First Remission, Treatment, and Outcomes.

Importance: Measurable residual disease (MRD) is widely used as a therapy-stratification factor for acute myeloid leukemia (AML), but the association of dynamic MRD with postremission treatment (PRT) in patients with intermediate-risk AML (IR-AML) has not been well investigated. Objective: To investigate PRT choices based on dynamic MRD in patients with IR-AML. Design, Setting, and Participants: This cohort study examined 549 younger patients with de novo IR-AML in the South China Hematology Alliance database during the period from January 1, 2012, to June 30, 2016, including 154 who received chemotherapy, 116 who received an autologous stem cell transplant (auto-SCT), and 279 who received an allogeneic SCT (allo-SCT). Subgroup analyses were performed according to dynamic MRD after the first, second, and third courses of chemotherapy. The end point of the last follow-up was August 31, 2020. Statistical analysis was performed from December 1, 2019, to September 30, 2020. Exposures: Receipt of chemotherapy, auto-SCT, or allo-SCT. Main Outcomes and Measures: The primary end points were 5-year cumulative incidence of relapse and leukemia-free survival. Results: Subgroup analyses were performed for 549 participants (314 male participants [57.2%]; median age, 37 years [range, 14-60 years]) according to the dynamics of MRD after 1, 2, or 3 courses of chemotherapy. Comparable cumulative incidences of relapse, leukemia-free survival, and overall survival were observed among participants who had no MRD after 1, 2, or 3 courses of chemotherapy. Participants who underwent chemotherapy and those who underwent auto-SCT had better graft-vs-host disease-free, relapse-free survival (GRFS) than those who underwent allo-SCT (chemotherapy: hazard ratio [HR], 0.35 [95% CI, 0.14-0.90]; P = .03; auto-SCT: HR, 0.07 [95% CI, 0.01-0.58]; P = .01). Among participants with MRD after 1 course of chemotherapy but no MRD after 2 or 3 courses, those who underwent auto-SCT and allo-SCT showed lower cumulative incidence of relapse (auto-SCT: HR, 0.25 [95% CI, 0.08-0.78]; P = .01; allo-SCT: HR, 0.08 [95% CI, 0.02-0.24]; P < .001), better leukemia-free survival (auto-SCT: HR, 0.26 [95% CI, 0.10-0.64]; P = .004; allo-SCT: HR, 0.21 [95% CI, 0.09-0.46]; P < .001), and overall survival (auto-SCT: HR, 0.22 [95% CI, 0.08-0.64]; P = .005; allo-SCT: HR, 0.25 [95% CI, 0.11-0.59]; P = .001) vs chemotherapy. In addition, auto-SCT showed better GRFS than allo-SCT (HR, 0.45 [95% CI, 0.21-0.98]; P = .04) in this group. Among participants with MRD after 1 or 2 courses of chemotherapy but no MRD after 3 courses, allo-SCT had superior cumulative incidence of relapse (HR, 0.10 [95% CI, 0.06-0.94]; P = .04) and leukemia-free survival (HR, 0.18 [95% CI, 0.05-0.68]; P = .01) compared with chemotherapy, but no advantageous cumulative incidence of relapse (HR, 0.15 [95% CI, 0.02-1.42]; P = .10) and leukemia-free survival (HR, 0.23 [95% CI, 0.05-1.08]; P = .06) compared with auto-SCT. Among participants with MRD after 3 courses of chemotherapy, allo-SCT had superior cumulative incidences of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.16 [95% CI, 0.08-0.33]; P < .001; leukemia-free survival: HR, 0.19 [95% CI, 0.10-0.35]; P < .001; overall survival: HR, 0.29 [95% CI, 0.15-0.55]; P < .001) and auto-SCT (relapse: HR, 0.25 [95% CI, 0.12-0.53]; P < .001; leukemia-free survival: HR, 0.35 [95% CI, 0.18-0.73]; P = .004; overall survival: HR, 0.54 [95% CI, 0.26-0.94]; P = .04). Among participants with recurrent MRD, allo-SCT was also associated with advantageous cumulative incidence of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.12 [95% CI, 0.04-0.33]; P < .001; leukemia-free survival: HR, 0.24 [95% CI, 0.10-0.56]; P = .001; overall survival: HR, 0.31 [95% CI, 0.13-0.75]; P = .01) and auto-SCT (relapse: HR, 0.28 [95% CI, 0.09-0.81]; P = .02; leukemia-free survival: HR, 0.30 [95% CI, 0.12-0.76]; P = .01; overall survival: HR, 0.26 [95% CI, 0.10-0.70]; P = .007). Conclusions and Relevance: This study suggests that clinical decisions based on dynamic MRD might be associated with improved therapy stratification and optimized PRT for patients with IR-AML. Prospective multicenter trials are needed to further validate these findings.

Diagnosis of Felty's syndrome, distinguished from hematological neoplasm: A case report.

Felty's syndrome (FS) is characterized by the three conditions of rheumatoid arthritis (RA), neutropenia and splenomegaly, and occurs in few cases of longstanding erosive RA. Discriminating between rare occurrences of autoimmune diseases and malignancies is crucial. The present study describes the case of a 17-year-old female with a two-year history of RA, presenting with an irregular fever, hepatosplenomegaly and enlarged lymph nodes. The antinuclear antibody titer was 1:320, while antibody results for anti-dsDNA, anti-Sm and rheumatoid factor were negative. The clinical presentation was similar to that of lymphoma. However, the fluorodeoxyglucose-positron emission tomography and biopsy examinations of the liver and cervical lymph node did not support the diagnosis of lymphoma. According to the laboratory results and clinical symptoms, the differential diagnosis indicated FS, and immunosuppressive agents were administered. Two weeks later, the patient no longer had a fever, and the transaminase levels were normal, associated with shrinkage of the liver and spleen.

Diagnosis and treatment of a patient with isolated spinal granulocytic sarcoma: A case report.

A previously healthy 34-year-old female presented with a 5-month history of progressive backache and weakness in the left fingers. Magnetic resonance imaging (MRI) showed soft tissue masses in the spinal canal distributed along the nerve course. The patient's baseline laboratory data were normal. Surgical intervention was performed and histological examination identified isolated spinal granulocytic sarcoma (GS). A bone marrow biopsy also presented normal findings. However, the patient developed numbness and pain in the right lower limb two months later. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) showed FDG uptake in the left trapezius muscle, cervix uteri, iliac bone, lymphadenectasis of the pelvic wall and left axillary fossa. Cerebrospinal fluid (CSF) examination allowed a diagnosis of central nervous system leukemia (CNSL). The patient underwent chemotherapy and intrathecal injection, resulting in the elimination of the residual lesion. Correct diagnosis and adequate treatment are essential to achieve optimal results in patients with isolated spinal GS.

Inhibition of extracellular signal-regulated kinase activity by sorafenib increases sensitivity to DNR in K562 cells.

The mitogen-activated protein kinase (MAPK) pathway has a protective function on the management of hematologic malignancies. The aim of this study was to assess whether the induction of MAPK-mediated effects contributes to the therapeutic value of combination sorafenib and daunorubicin (DNR) treatment. Herein, we found that DNR increased phosphorylation of extracellular signal-regulated kinases (ERK1/2) in K562 cells. ERK1/2 activity was blocked by either the mitogen-induced extracellular kinase (MEK) inhibitor U0126 or a multi-kinase inhibitor sorafenib. Of note, sorafenib sensitized K562 to DNR by inhibiting proliferation and inducing apoptosis in a dose-dependent manner which was through blocking the RAF/MEK/ERK pathway. Moreover, K562 cells transfected with a constitutively active MEK2DD plasmid showed increasing IC50 values following DNR treatment compared with control cells. Combination of DNR with MEK inhibitor U0126 synergistically inhibited K562 cell growth. In conclusion, our results indicated that sorafenib sensitized K562 cells to DNR-induced cytotoxicity by downregulating p-ERK1/2 expression. DNR in combination with sorafenib may represent a new and potential therapeutic strategy in treating acute leukemia with high p-ERK1/2 levels.

[Decitabine inhibits cell proliferation and induces apoptosis of all-trans retinoid acid-resistant acute promyelocytic leukemia NB4-R2 cell line].

The aim of this study was to investigate the proliferation-inhibitory and inducing apoptotic effects of decitabine (DAC) on acute promyelocytic leukemia NB4-R2 cells. Cell inhibitory rate was determined by cell proliferation and cytotoxicity assay (WST-1 assay) after NB4-R2 cells were treated with 0.01 - 0.5 µmol/L DAC for 24, 48 and 72 h. Apoptosis of NB4-R2 cells treated with 0.05 - 5 µmol/L DAC for 48 h was detected by flow cytometry with PI staining and AnnexinV/PI staining. Reverse transcription-PCR (RT-PCR) was used to determine the mRNA expression level of MDR1 gene encoding P-glycoprotein (P-gp). The results indicated that DAC (0.01 - 0.5 µmol/L) inhibited the proliferation of NB4-R2 cells in both time- and concentration-dependent manners. The IC(50) of DAC on the viability of NB4-R2 cells after treatment for 48 and 72 h were 0.089 and 0.064 µmol/L respectively. DAC (0.05 - 5 µmol/L) induced NB4-R2 cell apoptosis in dose-dependent manner with down-regulation of MDR 1 gene expression. It is concluded that a low concentration of DAC (< 0.5 µmol/L) inhibits cell proliferation, while higher concentration of DAC (1 or 5 µmol/L) induces apoptosis on NB4-R2 cells, accompanied with reduction of MDR1 levels.

[Sorafenib induces apoptosis of U937 cells via inhibiting WNT signal pathway].

This study was aimed to investigate the effect of multikinase inhibitor sorafenib on the proliferation and apoptosis of U937 cells and its possible mechanism. U937 cells were treated with different concentrations of sorafenib for 48 hours. Cell viability was determined by Cell Counting Kit-8; cell apoptosis and cell ratio in cell cycle were detected by flow cytometry with Annexin V/PI staining and PI staining respectively; expressions of GSK-3ß, ß-catenin and cyclin-D1 were assayed by Western blot. The results showed that the proliferation of U937 cells was inhibited by sorafenib in a dose-dependent manner (p < 0.05). Sorafenib induced cell apoptosis and cell cycle G(1)/G(0) arrest. Compared with results of Western blot before treatment, expression of inactivated GSK-3ß, ß-catenin and Cyclin-D1 down-regulated in a dose-dependent manner after treatment with sorafenib, this same changes were observed after up-regulation of inactivated GSK-3ß by LiCl (p < 0.05). It is concluded that sorafenib inhibits the proliferation of U937 cells and induces cell apoptosis through reducing negative regulation of WNT signal pathway on inactivated GSK-3ß and down-regulating ß-catenin and cyclin-D1 level, which result in U937 cell cycle G(1)/G(0) arrest.