From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

Several programmed cell death protein 1 (PD-1) or its ligand (PD-L1) immune checkpoint blocking antibodies are available for clinical treatment, but only some patients show clinical response, so an alternative strategy for tumor immunotherapy is needed.A therapeutic tumor vaccine targeting PD-L1 is a meaningful attempt.In this study, we designed an epitope peptide vaccine targeting PD-L1, and then screened the immunogenic PD-L1 epitope peptide based on the humanized immune system (HIS) mouse model and further investigated its anti-tumor activity.The results show that the designed and screened PD-L1-B1 epitope peptide vaccine not only successfully induced PD-L1-specific humoral and cellular immunity, but also exhibit anti-tumor activity.In addition, immunotherapy increased T-lymphocyte infiltration of tumors and reshaped the tumor immunosuppressive microenvironment.In conclusion, PD-L1-B1 epitope peptide vaccine exhibits potent anti-tumor activity and may be an effective alternative immunotherapeutic strategy for patients insensitive to PD-1/PD-L1 blockade.

Humans ; Multiple Myeloma/genetics* ; Karyotyping ; Translocation, Genetic/genetics*

Objective:To investigate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (RVD) in patients with newly diagnosed multiple myeloma (NDMM).Methods:A total of 100 consecutive NDMM patients treated with RVD from August 2016 to September 2020 at Peking University People′s Hospital were retrospectively analyzed, including response, drug toxicity, follow-up and survival, and subgroup analysis.Results:The median follow-up time was 19.5 (2.0-57.0) months. For patients undergoing autologous stem cell transplantation (ASCT) after RVD regimen, the objective response rate (ORR)/complete response+stringent complete response (CR+sCR)/≥very good partial response (VGPR) rates were 100%, 73.3% (33/45), 95.6% (43/45) respectively. For 54 patients not receiving transplantation, the ORR/CR+sCR/≥VGPR rates were 79.6% (43/54), 18.5% (10/54), 51.9% (28/54) respectively. As to the survival analysis, 2-year progression free survival (PFS) rates were 84.5% and 70.9% in transplant and non-transplant patients respectively ( P=0.102). Two-year overall survival (OS) rates were 100% and 80.8% in transplant and non-transplant patients respectively ( P=0.003). The common hematologic adverse events (AEs) were thrombocytopenia (33%) and neutropenia (25%). Abnormal liver function (43%) and peripheral neuropathy (24%) were recognized more as non-hematologic AEs. Conclusion:RVD as front-line regimen has high efficient response rate and acceptable safety in Chinese NDMM patients.

Objective:This study aimed to explore variables associated with remission rate and survival in patients with acute myeloid leukemia (AML) after induction failure and relapse.Methods:Data of 373 consecutive patients with AML were analyzed after induction failure and relapse. Binary logistics and the Cox model regression were used to identify variables associated with remission rate and outcomes.Results:In patients with AML after induction failure and relapse, the total CR+CRi rates were 50.6% and 40.3%, respectively; among those who achieved CR/CRi, the 3-year RFS rates were 34.4% and 30.4%, respectively, and the 3-year overall survival rates were 40.1% and 31.6%, respectively. In the multivariate analyses, using CLAG or FLAG regimen as a re-induction chemotherapy regimen, age <39 years and SWOG low-risk were significantly associated with higher remission rates in patients with induction failure. Male, secondary AML, SWOG high-risk, the interval from the first remission to relapse within 12 months, and bone marrow blasts ≥20% at the time of relapse were significantly associated with lower remission rates in relapsed patients. Transplantation was significantly associated with prolonged relapse-free survival and overall survival in patients achieving hematologic remission; the SWOG low-risk group was significantly associated with longer overall survival in those with induction failure; and achieving CR (not CRi) or having female gender was associated with longer RFS or overall survival in relapsed patients.Conclusion:Reinduction chemotherapy regimen, age, gender, SWOG risk, secondary AML, the interval from the first remission to relapse, and bone marrow blast percentage at the time of relapse were significantly associated with remission rates in the patients with AML after induction failure and relapse. Transplantation, SWOG low-risk, achieving CR, or female gender were associated with longer survivals in those achieving remission.

Objective:To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis.Methods:Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed.Results:All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients.Conclusion:Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.

Objective:To analyze the effect and safety of plerixafor combined with G-CSF mobilization in plasma cell disease.Methods:The clinical baseline data, success rate of collection, and adverse reactions of consecutive cases of plasma cell disease were analyzed retrospectively, where the patients received plerixafor combined with G-CSF for autologous hematopoietic stem cell mobilization in Peking University People's Hospital from January 2018 to December 2019.Results:Forty-nine patients with plasma disease were included, of which 39 (79.6% ) were multiple myeloma, 8 (16.3% ) were amyloidosis, and 2 (4.1% ) were monoclonal gammopathy of renal significance. A total of 16 patients (32.7% ) had renal insufficiency, and 7 patients (14.3% ) had previous collection failure. The median times of apheresis was 1 (1-3) , median days of apheresis was 2 (1-3) days, 47 patients (95.9% ) were successfully collected for once, and the success rate of collection for twice was 100% after using plerixafor for mobilization. In 16 patients with renal insufficiency, collection was successful in 5 patients (31.3% ) on the first day, while aphresis was required in 8 patients (50% ) on the second day and 3 (18.8% ) on the third day. The main adverse reactions were fatigue, insomnia, abdominal pain, diarrhea, dizziness, and arthralgia. A total of 37 patients underwent autologous hematopoietic stem cell transplantation with 11 (8-13) days for neutrophil engraftment, and 11 (9-26) days for platelet engraftment.Conclusions:Plerixafor combined with G-CSF has a high success rate in mobilizaion of autologous hematopoietic stem cells in patients with plasma cell disease with minimum side effects, even in patients with renal insufficiency.

Objective:To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM).Methods:The efficacy and adverse events (AEs) of daratumumab based regimens were retrospectively analyzed in 37 patients with RRMM from Peking University People′s Hospital, Beijing Hospital and Fu Xing Hospital affiliated to Capital Medical University in China. The deadline for inclusion was December, 2019.Results:Among the 37 patients, 35 patients were available for response evaluation. The overall response rate (ORR) was 68.6%, which was better in patients receiving 16 mg/kg daratumumab than in those with fixed doses of 800 mg daratumumab [ORR: 78.3%(18/23) vs. 40.0%(4/10)]. The percentage of infusion related reactions of daratumumab was 27.0%(10/37). The most common hematological AEs were lymphocytopenia and thrombocytopenia, with the incidences of grade 3 or more severe 59.5%(22/37) and 43.2%(16/37) respectively. Pulmonary infections(37.8%, 14/37) were the most common non-hematological AEs. One patient with positive hepatitis B surface antigen (HBsAg) and two patients dependent on dialysis were safely treated with daratumumab.Conclusion:Daratumumab is highly effective in relapsed and refractory multiple myeloma. Adverse reactions are mild and well tolerable.

Objective:To investigate the clinical manifestation, diagnosis and prognosis of heavy- and light-amyloidosis (AHL).Methods:The clinical data of two patients with AHL in Peking University People's Hospital and 21 cases of reported literature were reviewed to clarify the clinical and prognostic characteristics of AHL.Results:Compared with light-amyloidosis, most AHL patients were male, with high positive rate of blood and urine immunofixation electrophoresis and complete immunoglobulin. The manifestations of the kidneys were proteinuria, mainly composed of albumin, nephrotic syndrome and microscopic haematuria. The pathology of renal biopsy showed that Congo red staining positive substances were deposited in many sites (mesangial area, capillary wall, arteriole and renal interstitium), and immunofluorescence showed that monoclonal heavy chain with light chain (the type was consistent with the hematuria M protein) were clumpy deposition, which was consistent with amyloid deposition site. Heart involvement was rare, and the proportion of plasma cells in bone marrow was high.Conclusion:AHL is rare and its clinical manifestations of AHL are different from those of light-amyloidosis. The prognosis needs to be further observed.

Objective:To investigate the characteristics of T cell immunophenotype and its relationship with clinical manifestation in patients with systemic light chain amyloidosis (AL) .Methods:The peripheral blood mononuclear cells from 36 patients with AL were collected and analyzed by multicolor flow cytometry, and the expression of surface antigen CD3, CD56, CD4, CD8, CD25, CD45RA, CD28, CD57 and nuclear antigen FOXP3 were examined. Samples from 28 age-matched healthy donors (HD) were also examined. Patients were divided by Mayo 2012 staging system and the difference between immunophenotype of Ⅰ-Ⅱ and Ⅲ-Ⅳ stage patients were analyzed. The correlations between the proportion of T-cell subpopulation and clinical manifestations in λ light chain type AL patients were analyzed.Results:The differences in the peripheral total T cells and T cell subsets, including CD4 +, CD8 +, regulatory T cells, and natural killer T cells were not significantly between AL and HD. The ratio of CD57 + cells in CD8 + T cells was lower in AL than in HD, and there was no significantly difference in the rate of CD45RA + and CD28 +cells between these two groups. No differences were found in the ratio of total T cells or T cell subsets between stages Ⅰ-Ⅱ and Ⅲ-Ⅳaccording to the standard of Mayo 2012. Within λ light chain type AL patients, peripheral CD8 + T cell ratio was positively correlated with 24-hour urine protein and creatinine level and negatively correlated with estimated glomerular filtration rate (eGFR) . Conclusion:The overall T cell distribution in the periphery is not significantly different between AL patients and age-matched healthy donors. However, the percentages of CD8 + T cells are positively correlated with renal injury, indicating the importance of CD8 + T cell subset in the prognostic evaluation of renal involvement.