Germline variants in acquired aplastic anemia: current knowledge and future perspectives.

Aplastic anemia (AA) is a disease characterized by hematopoiesis failure, bone marrow aplasia, and pancytopenia. It can be inherited or acquired. Although acquired AA is believed to be immune-mediated and random, new evidence suggests an underlying genetic predisposition. Besides confirmed genomic mutations that contribute to inherited AA (such as pathogenic mutations of TERT and TERC), germline variants, often in heterozygous states, also play an unignorable role in the onset and progression of acquired AA. These variants, associated with inherited bone marrow failure syndromes (IBMFS) and inborn errors of immunity (IEI), contribute to the disease possibly through mechanisms including gene homeostasis, DNA repair, and immune injury. This article explores the nuanced association between acquired AA and germline variants, detailed the clinical significance of germline variants in diagnosing and clinical management of this condition. More works are encouraged to better understand the role of immunogenic pathogenic variants and whether somatic mutation participate as secondary "hit" in the development of bone marrow failure.

Prolonged haematologic toxicity in CAR-T-cell therapy: A review.

Chimeric antigen receptor-T-cell (CAR-T-cell) therapy is a novel immunotherapy with encouraging results for treatment of relapsed/refractory haematologic malignancies. With increasing use, our understanding of immune-mediated side effects such as cytokine release syndrome and neurotoxicity has improved; nevertheless, prolonged haematologic toxicity (PHT), with a high incidence rate, remains underrecognized. Owing to heterogeneity in populations, the CAR-T cells used and diseases treated as well as differences in the definition of PHT, its rate, risk factors and management vary across studies. In this review, we provide a narrative of PHT occurring in patients following CAR-T-cell therapy; evidence of PHT treatment strategies is also presented, with the aim of contributing to systematic understanding of PHT.

Comparison of haploidentical-allogeneic hematopoietic stem cell transplantation and intensive immunosuppressive therapy for patients with severe aplastic anemia with an absolute neutrophil count of zero: a retrospective study.

A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical-allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0% vs. 40.0%, P = 0.001; 80.0% vs. 17.1%, P = 0.001). With a median follow-up of 18.5 months (4.3~30.8 months), patients in the HID-HSCT group had longer overall survival and event-free survival (80.0% vs. 47.9%, P = 0.0419; 79.2% vs. 33.5%, P = 0.0048). These data suggested that HID-HSCT might be an effective alternative treatment option for adult patients with SAA with an ANC of zero, which requires further validation in an additional prospective study.

Whole-exome sequencing identifies FANC heterozygous germline mutation as an adverse factor for immunosuppressive therapy in Chinese aplastic anemia patients aged 40 or younger: a single-center retrospective study.

Acquired aplastic anemia (AA) is a bone marrow failure disorder characterized by pancytopenia, and immunosuppressive therapy (IST) is the optional first-line management. Several studies identified the influencing factors on IST response; however, there are still a considerable number of patients suffering from poor prognoses. In this study, we enrolled 61 AA patients aged ≤ 40 years old, and whole-exome sequencing (WES) found unexpected high FANC heterozygous germline mutations (28/61, 45.9%). Patients with FANC mutations have a significantly lower absolute reticulocyte count and CD34+ % in the bone marrow and also lower 3-, 6-, and 9-month IST response than that without mutation, which were 0% vs. 25% (P = 0.017), 26.3% vs. 42.1% (P = 0.495), and 29.4% vs. 72.2% (P = 0.011), especially in anti-thymocyte globulin combined with the cyclosporin A (ATG + CsA) group, which were 0% vs.33.4% (P = 0.143), 25% vs.83.3% (P = 0.103), and 25% vs. 100% (P = 0.003), respectively. The event-free survival in the FANCwt group was also better than that in the FANCmut group (P = 0.016) and also showed in patients who received ATG + CsA treatment (P = 0.045). In addition, all the adverse effects of FANC germline mutation were not significant in stem cell-transplanted group. Our result indicated that the WES-based detection of FANC heterozygous germline mutations may have a great meaning in predicting IST response of acquired AA. This study was registered at chictr.org.cn (# ChiCTR2100054992).

Research progress on the hematopoietic microenvironment in aplastic anemia.

Aplastic anemia (AA) is a disease of bone marrow hematopoietic failure, and the main clinical manifestation is pancytopenia. Its pathogenesis is still unclear. In recent years, more research has been done on its immune abnormalities to explain its pathogenesis and less on the hematopoietic microenvironment, but there are still some advances. This article summarizes the research on the hematopoietic microenvironment of AA in recent years to provide new ideas for the clinical treatment of AA.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Effectiveness of prophylactic antiviral therapy in reducing HBV reactivation for HBsAg-positive recipients following allogeneic hematopoietic stem cell transplantation: a multi-institutional experience from an HBV endemic area.

Hepatitis B virus reactivation (HBVr) is not uncommon in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Hepatitis B surface antigen (HBsAg)-positive patients receiving allo-HSCT have a very high risk of HBVr. However, the validity of prophylactic antiviral treatment in HBsAg-positive allo-HSCT recipients has not been well studied. We aimed to add experience in dealing with HBsAg-positive patients following allo-HSCT. We conducted a cohort study that included 11 years of data of HBsAg-positive allo-HSCT patients in multiple centers. The cumulative incidence of HBVr with antiviral prophylaxis at 60 months following transplantation was 8.9%. Both lamivudine (LAM) and entecavir (ETV) effectively reduced the incidence of HBVr. Patients with absent-mild cGVHD had a lower HBVr rate than that of patients with moderate-severe cGVHD (HR = 0.201, P = 0.020). The incidence of HBsAg seroclearance at 60 months following transplantation was 34.3%. Recipients accepting from anti-HBs-negative donors were associated with a lower HBsAg seroclearance rate than that of those accepting from anti-HBs-positive donors (HR=0.255, P < 0.001). The peripheral blood stem cell (PBSC) donor source had a higher HBsAg seroclearance rates than that of the PBSC plus bone marrow stem cell source (HR = 4.700, P = 0.047). The prophylactic antiviral treatment effectively reduced HBVr in HBsAg-positive recipients receiving allo-HSCT. HBsAg-positive recipients accept anti-HBs-positive PBSC donor sources may facilitate the acquisition of HBsAg seroclearance after transplantation.

Outcome after allogeneic hematopoietic stem cell transplantation following Venetoclax-based therapy among AML and MDS patients.

The use of Bcl-2 inhibitor Venetoclax (VEN) combined with hypomethylating agents or chemotherapy has shown efficacy in treating acute myeloid leukemia (AML) as frontline treatment and for relapse, allowing more patients to bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the influence of VEN-based therapy on the prognosis of subsequent allogeneic HSCT remains unknown. We retrospectively collected data from patients who proceeded to allo-HSCT between November 2018 and November 2020 after VEN-based therapy at five transplant centers in Zhejiang Province, China. A total of 39 patients were analyzed. Thirty-one patients were diagnosed with AML (28 de novo, 3 secondary to MDS), 6 with MDS, and 2 with CMML. The majority (74.4%) of patients received VEN-based therapy for the treatment of relapse (38.5%) or refractory disease (35.9%); 5 (12.8%) received it as an initial treatment, and 5 (12.8%) patients who were already in complete remission (CR) received VEN for further consolidation or deep remission before HSCT. Twenty-seven (69.2%) patients were in CR at the time of HSCT. Day + 100 cumulative incidences of grade I-IV acute graft-versus-host disease (aGVHD) and grade II-IV aGVHD were 43.6% and 15.4%, respectively. Of 34 evaluable patients, 6.4% and 25.6% developed chronic GVHD at 1 year and 2 years. The 100-day cytomegalovirus (CMV) reactivation occurred in 76.3% of patients and Epstein-Barr virus (EBV) reactivation occurred in 29.7% of patients. With a median follow-up of 14.7 months, overall survival, progression-free survival, relapse, and non-relapse mortality incidence at 1 year were 75.5%, 61.6%, 16.7%, and 21.7%, respectively. Both univariate and multivariate analysis revealed that relapsed/refractory (R/R) disease was associated with inferior PFS (HR 4.849, 95% CI 1.009-23.30; p = 0.049). Prior poor response to VEN was found to be a significant factor predicting higher risk of relapse (HR 4.37, 95% CI 1.130-16.9; p = 0.033). Our results showed that VEN-based regimen therapy followed by allo-HSCT in AML patients is feasible and does not increase the risk of transplant-related mortality and toxicity.

Effect of avatrombopag in the management of severe and refractory chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors.

Chemotherapy-induced thrombocytopenia (CIT) is a common complication in cancer patients, especially after multiple cycles of chemotherapy, which leads to the delayed treatment or reduced dosage. The treatment of CIT is limited for refractory and severe cases. Herein we reported a single-center study of avatrombopag, a type of thrombopoietin receptor agonist (TPO-RA), for the treatment of severe and refractory (S/R) CIT who failed from multi-line treatments. A total of 13 cancer patients with S/R CIT were enrolled at the First Affiliated Hospital of Zhejiang Chinese Medical University from September 2020 to February 2021. All the patients were administered oral avatrombopag at an initial dose of 60 mg/day, which could be decreased as needed, over a period of 8 weeks. Eight (8/13, 61.5%) patients responded to avatrombopag (with a platelet count ≥50 × 109/L and transfusion independent), with a median response time of 27.5 (11-50) days, and the median cumulative day of platelet response was 79 (20-167). Ten of 13 patients (76.9%) no longer required platelet transfusion at the study endpoint. The predictor of response was the level of hemoglobin (HB) at study entry, patients with an HB over 90 g/L achieved a response rate of 88.9%. In addition, platelet count showed 87.5% sensitivity and 100% specificity to predict the treatment response at a cutoff value of 25.5× 109/L at the end of the third week management. No drug-related side effects were noticed during administration. Our study showed that avatrombopag could be a novel and effective drug for the treatment of severe and refractory CIT, especially for those with hemoglobin above 90 g/L. This study was registered at chictr.org.cn as # ChiCTR2100050646.

Apolipoprotein-A is a potential prognostic biomarker for severe aplastic anemia patients treated with ATG-based immunosuppressive therapy: a single-center retrospective study.

BACKGROUND: Anti-thymoglobulin (ATG)-based immunosuppressive treatment (IST) is the standard first-line management for patients with severe AA/very severe AA (SAA/VSAA) and is not suitable for allogeneic stem cell transplantation. The response predictor was not fully investigated. OBJECTIVE: The present study attempted to explore other characteristics, such as serum lipid changes, during ATG-based IST and analyzed their significance in predicting IST response and survival. METHODS: A total of 61 newly diagnosed SAA/VSAA patients who received ATG-based IST were enrolled from January 2011 to June 2019. The blood lipid levels, immunoglobulins, and peripheral T lymphocytes were retrospectively collected, and their correlations with IST response, estimated 8.5-year overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: The overall response (OR)/complete remission (CR) at 3, 6, and 9 months was 24.6%/6.6%, 52.5%/14.8%, and 65.6%/23.0%, respectively. Based on the 9-month response effect, patients were divided into IST-response (IST-R) and IST-nonresponse (IST-NR) groups. The subgroup baseline characteristics showed that the disease severity grade, absolute neutrophil granulocyte count (ANC), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein-A (Apo-A) differed between the IST-R and IST-NR groups. Patients with lower Apo-A (< 1.205 g/L) level pretreatment had a better event-free survival (EFS), and a moderate negative correlation was established between the pretreatment Apo-A and 9-month response (P = 0.004). In addition, the T-cell subset and immunoglobulin analyses showed that the responsive patients had a low serum IgA level, which decreased further after therapy. Additionally, a moderate negative correlation was established between the 3-month IgA and 9-month response (P = 0.006). CONCLUSION: Serum Apo-A is a prognostic biomarker for newly diagnosed < 60-year-old SAA/VSAA patients who received ATG-based IST (registered at chictr.org.cn as # ChiCTR2100052979).

Quantifying Bone Marrow Fat Fraction and Iron by MRI for Distinguishing Aplastic Anemia from Myelodysplastic Syndromes.

BACKGROUND: Bone marrow of patients with aplastic anemia (AA) is different from that of patients with myelodysplastic syndrome (MDS) and is difficult to identify by blood examination. IDEAL-IQ (iterative decomposition of water and fat with echo asymmetry and least-squares estimation) imaging might be able to quantify fat fraction (FF) and iron content in bone tissues. PURPOSE: To determine if IDEAL-IQ measurements of bone marrow FF and iron content can distinguish between patients with AA and MDS. STUDY TYPE: Retrospective. POPULATION: Fifty-seven patients with AA, 21 patients with MDS, and 24 healthy controls. FIELD STRENGTH/SEQUENCE: 3.0 T, IDEAL-IQ sequence. ASSESSMENT: Three independent observers evaluated the IDEAL-IQ images and measured FF and R2* in the left posterior superior iliac spine. STATISTICAL TESTS: Kruskal-Wallis test, linear correlations, and Bland-Altman analysis were used. A P-value of <0.05 was considered statistically significant. RESULTS: The FF in patients with AA (79.46% ± 15.00%) was significantly higher than that in patients with MDS (42.78% ± 30.09%) and control subjects (65.50% ± 14.73%). However, there was no significant difference in FF between control subjects and patients with MDS (P = 0.439). The R2* value of AA, MDS, and controls was 145.38 ± 53.33, (171.13 ± 100.89, and 135.99 ± 32.41/second, respectively, with no significant difference between the three groups (P = 0.553). DATA CONCLUSION: Quantitative IDEAL-IQ magnetic resonance imaging may facilitate the diagnosis of AA and distinguish it from MDS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Autophagy and Ubiquitin-Mediated Proteolytic Degradation of PML/Rarα Fusion Protein in Matrine-Induced Differentiation Sensitivity Recovery of ATRA-Resistant APL (NB4-LR1) Cells: in Vitro and in Vivo Studies.

BACKGROUND/AIMS: Although the cure rate of acute promyelocytic leukemia (APL) has exceeded 90%, the relapse/refractory APL that resistant to all-trans retinoic acid (ATRA) or ATO was still serious concern. Matrine (MAT) could improve the differentiation ability of ATRA-resistant APL cells. This study aimed to explore how the APL-specific fusion protein was degraded in ATRA-resistant APL with the application of MAT and ATRA. METHODS: ATRA-sensitive (NB4) and ATRA-resistant (NB4-LR1) cell lines were used. Nitroblue tetrazolium reduction assay and flow cytometry were used to detect the differentiation ability. The activity of ubiquitin-proteasome and autophagy-mediated pathways in both cells treated with ATRA with or without MAT were compared in protein and mRNA level (Western blot analysis, qRT-PCR), the Fluorescent substrate Suc-LLVY-AMC detection was used to detect the activity of proteasome, and electron microscope for observing autophagosome. MG 132(proteasome inhibitor), rapamycin (autophagy activator), hydroxychloroquine (lysosomal inhibitor) and STI571 [retinoic acid receptor alpha (RARα) ubiquitin stabilizer] were used as positive controls. The effect of MAT was observed in vivo using xenografts. RESULTS: MAT improved the sensitivity of NB4-LR1cells to ATRA treatment, which was consistent with the expression of PML-RARα fusion protein. MAT promoted the ubiquitylation level in NB4-LR1. MG 132 induced the decrease in RARα in both cell lines, and hampered the differentiation of NB4 cells. MAT also promoted the autophagy in NB4-LR1 cells, with an increase in microtubule-associated protein 1 light chain3 (LC3)-II and LC3-II/LC3-I ratio and exhaustion of P62. The expression of LC3II increased significantly in the MAT and ATRA + MAT groups in combination with lysosomal inhibitors. A similar phenomenon was observed in mouse xenografts. MAT induced apoptosis and differentiation. CONCLUSIONS: Autophagy and ubiquitin-mediated proteolytic degradation of PML/RARα fusion protein are crucial in MAT-induced differentiation sensitivity recovery of NB4-LR1 cells.

Successful use of rituximab in platelet transfusion refractoriness in a multi-transfused patient with myelodysplastic syndrome.

A 61-year-old man with newly diagnosed INT-1 risk myelodysplastic syndrome--refractory cytopenia with multilineage dysplasia (MDS-RCMD) was not responsive to treatment, such as androgen, thalidomide, granulocyte--colony stimulating factor (G-CSF) combined with erythropoietin (EPO), interleukin-11 (IL-11) and thrombopoietin (TPO), and became transfusion dependent. Due to repeated blood transfusions, he developed platelet transfusion refractoriness (PTR) to platelets from cross-matched donors as well as random donors. Anti-HLA class I antibodies were positive with enzyme-linked immunosorbent assay; however, HLA-compatible platelet products were unavailable. PTR was unresponsive to high-dose immunoglobulin and plasma exchange. The patient was then treated with rituximab 375 mg/m(2) on days 1 and 8, and 100 mg total dose on days 15 and 22. Already after the first dose of rituximab, the patient was able to received successful platelet transfusion from all donors. Therefore rituximab may be considered as a potential therapy for PTR.

[Significance of PLSCR1 in Matrine Induced Differentiation of ATRA Resistant APL Cells].

OBJECTIVE: To observe the expression of phospholipid scramblase 1 (PLSCR1) in matrine (MAT) induced differentiation of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) cells, and to explore its correlation to cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signal pathway. METHODS: NB4 (an APL cell line sensitive to ATRA) and NB4-R1 (a resistant strain of ATRA) were observed as subjects in this study. Effects of combined treatment of 0.1 mmol/L MAT and 1 [mol/L ATRA on the differentiation of two cell lines were detected using nitroblue tetrazolium (NBT) reduction test and flow cytometry (CD11b). Expressions of PML/RARot and PLSCR1 protein/gene were detected using Western blot and Real-time fluorescence quantitative PCR assay. Meanwhile, H89, PKA antagonist, was used to observe cell differentiation antigen and changes of aforesaid proteins and genes. RESULTS: MAT combined ATRA could significantly elevate positive rates of NBT and CD11 b in NB4-R1 cells, and significantly down-regulate the expression of PML/RARapha-fusion protein/gene (P < 0.05, P < 0.01). ATRA used alone could obviously enhance the expression of PLSCRI in NB4 cells at protein and mRNA levels (P < 0.01). But the expression of PLSCR1 was up-regulated in NB4-R1 cells, but with statistical.difference only at the protein level (P <0. 01). In combination of MAT, PLSCR1 protein expression was further elevated in the two cell lines (P < 0.01). Besides, there was statistical difference in mRNA expressions in NB4-R1 cells (P < 0.05). All these actions could be reversed by treatment of 10 micromol/L H89 (P < 0.05, P < 0.01). CONCLUSION: MAT combined ATRA could significantly induce the differentiation of NB4-R1 cells, and inhibit the expression of PML/RARalpha fusion gene/protein, which might be associated with up-regulating PLSCR1 expression.

[Treatment of myelodysplastic syndrome by hematopoietic stem cell transplantation combined with Chinese medical syndrome typing: a clinical study].

OBJECTIVE: To evaluate the clinical efficacy of treating myelodysplastic syndrome (MDS) by hematopoietic stem cell transplantation (HSCT) combined with Chinese medical syndrome typing. METHODS: From July 2009 to July 2013, 6 MDS patients were treated with allo-HSCT combined with Chinese medical syndrome typing from HLA-identical sibling donors at Department of Hematology, Zhejiang Provincial Hospital of Chinese Medicine. Patients were classified as refractory anemia (RA, 2 cases), refractory anemia with ringed sideroblast (RARS, 1 case), refractory cytopenia with multilineage dysplasia (RCMD, 2 cases), and RA with excess blasts-I (RAEB-I , 1 case). Modified BuCy conditioning regimen was used in all 6 cases. Two patients received bone marrow transplantation (BMT), 1 patient received peripheral blood stem cell transplantation (PBSCT), and 3 patients received BMT + PBSCT. In order to prevent the occurrence of graft-versus-host disease (GVHD), all patients were treated with cyclosporine + methotrexate + mycophenolate mofetil. Different Chinese medical treatment methods (by syndrome typing) were given to patients according to different criticality of international prognostic scoring system (IPSS, 5 at moderate risk and 1 at high risk). RESULTS: All 6 patients successfully reconstructed their hematopoietic system. The time from transplantation to ANC ≥ 0.5 x 10(9)/L and platelet (PLT) ≥ 20 x10(9)/L were 13 (9-15) days and 11 (9-22) days respectively. Main complications were GVHD. Acute GVHD (aGVHD) occurred in 4 cases, 3 cases of grade I and 1 case of grade II, and local chronic GVHD (cGVHD) occurred in 1 patient. All cases survived with median follow-up of 18 (11-58) months. The overall survival (OS) and disease-free survival (DFS) rate were 100%. CONCLUSIONS: HSCT combined with Chinese medical syndrome typing could improve clinical symptoms, reduce transplant as- sociated complications. So it was an effective treatment choice for MDS.

Matrine cooperates with all-trans retinoic acid on differentiation induction of all-trans retinoic acid-resistant acute promyelocytic leukemia cells (NB4-LR1): possible mechanisms.

Retinoic acid resistance results in refractory disease, and recovery in acute promyelocytic leukemia remains a challenge in clinical practice, with no ideal chemotherapeutic drug currently available. Here we report on the effect of an active compound of Sophora flavescens called matrine (0.1 mmol/L) combined with all-trans retinoic acid (1 µmol/L) in alleviating retinoic acid resistance in acute promyelocytic leukemia-derived NB4-LR1 cells by differentiation induction, as can be seen by an induced morphology change, increased CD11b expression, and nitro blue tetrazolium reduction activity, and a decreased expression of the promyelocytic leukemia-retinoic acid receptor α fusion gene and protein product. We further explored the probable mechanism of how matrine promotes the recovery of differentiation ability in NB4-LR1 cells when exposed to all-trans retinoic acid. We observed that the combination of all-trans retinoic acid and matrine can increase the level of cyclic adenosine monophosphate and protein kinase A activity, reduce telomerase activity, and downregulate the protein expression of topoisomerase II beta in NB4-LR1 cells. The results of this study suggest the possible clinical utility of matrine in the treatment of retinoic acid-resistant acute promyelocytic leukemia.

Myelodysplastic syndrome with IgG4­related disease: A case report.

At present, to the best of our knowledge, there are only a few case reports of IgG4-related disease (IgG4-RD) involving myelodysplastic syndrome (MDS), yet the incidence of MDS and IgG4-RD is increasing in middle-aged and elderly people. The present study presents a case of MDS combined with IgG4-RD admitted to Zhejiang Provincial Hospital of Chinese Medicine in September 2022. The (66-year-old; male) patient was admitted to the hospital due to hematopenia with an elevated IgG4 index. The diagnosis of MDS combined with IgG4-RD was confirmed after various exams, including pathological examination. The condition of the patient improved after 3 weeks of hormone therapy, with a significant increase in complete blood count compared with the pre-treatment period. MDS is a malignant hematological disorder with a high risk of conversion to leukemia, and IgG4-RD is a systemic immune-mediated disease with a poor prognosis often associated with malignancy. The present study presents and reviews the literature to better understand the coexistence of these two diseases.