Combinational therapy of CAR T-cell and HDT/ASCT demonstrates impressive clinical efficacy and improved CAR T-cell behavior in relapsed/refractory large B-cell lymphoma.

BACKGROUND: Approximately two-thirds of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) do not respond to or relapse after anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, leading to poor outcomes. Previous studies have suggested that intensified lymphodepletion and hematological stem cell infusion can promote adoptively transferred T-cell expansion, enhancing antitumor effects. Therefore, we conducted a phase I/II clinical trial in which CNCT19 (an anti-CD19 CAR T-cell) was administered after myeloablative high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in patients with R/R LBCL. METHODS: Transplant-eligible patients with LBCL who were refractory to first-line immunochemotherapy or experiencing R/R status after salvage chemotherapy were enrolled. The study aimed to evaluate the safety and efficacy of this combinational therapy. Additionally, frozen peripheral blood mononuclear cell samples from this trial and CNCT19 monotherapy studies for R/R LBCL were used to evaluate the impact of the combination therapy on the in vivo behavior of CNCT19 cells. RESULTS: A total of 25 patients with R/R LBCL were enrolled in this study. The overall response and complete response rates were 92.0% and 72.0%, respectively. The 2-year progression-free survival rate was 62.3%, and the overall survival was 68.5% after a median follow-up of 27.0 months. No unexpected toxicities were observed. All cases of cytokine release syndrome were of low grade. Two cases (8%) experienced grade 3 or higher CAR T-cell-related encephalopathy syndrome. The comparison of CNCT19 in vivo behavior showed that patients in the combinational therapy group exhibited enhanced in vivo expansion of CNCT19 cells and reduced long-term exhaustion formation, as opposed to those receiving CNCT19 monotherapy. CONCLUSIONS: The combinational therapy of HDT/ASCT and CNCT19 demonstrates impressive efficacy, improved CNCT19 behavior, and a favorable safety profile. TRIAL REGISTRATION NUMBERS: ChiCTR1900025419 and NCT04690192.

Genotype-degree of hemolysis correlation in hereditary spherocytosis.

BACKGROUND: Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt's carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation. RESULTS: In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8-48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13 (8-23), 13 (8-48) and 14 (12-39) days, respectively, with no statistically significant difference (P = 0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8-48), 14 (11-40) and 13 (8-20) days, respectively, with no significant difference (P = 0.514). Similarly, we found no significant difference in the RBC lifespan of patients with mutations located in the spectrin-binding domain and the nonspectrin-binding domain [14 (8-18) vs. 12.5 (8-48) days, P = 0.959]. In terms of the composition of mutated genes, 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations, while 75% of patients with mild hemolysis carried SPTB or SLC4A1 mutations. In contrast, 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% of patients with severe hemolysis had SPTB or SLC4A1 mutations. However, there was no statistically significant difference in the distribution of mutated genes between the two groups (P = 0.400). CONCLUSION: The present study is the first to investigate the potential association between genotype and degree of hemolysis in HS. The present findings indicated that there is no significant correlation between genotype and degree of hemolysis in HS.

Iron overload due to SLC40A1 mutation of type 4 hereditary hemochromatosis.

Hereditary hemochromatosis type 4 is an autosomal-dominant inherited disease characterized by a mutation in the SLC40A1 gene encoding ferroportin. This condition can be further subdivided into types 4A (loss-of-function mutations) and 4B (gain-of-function mutations). To date, only a few cases of type 4B cases have been reported, and the treatment has not been clearly mentioned. Here, we report a genotype of hereditary hemochromatosis type 4B involving the heterozygous mutation c.997 T > C (p. Tyr333His) in SLC40A1. The patient was treated with red blood cell apheresis every month for 1 year, followed by oral deferasirox, and the combined therapy was found to be effective.

Hetrombopag plus porcine ATG and cyclosporine for the treatment of aplastic anaemia: early outcomes of a prospective pilot study.

Hetrombopag, a small molecular thrombopoietin-receptor agonist, has shown encouraging efficiency in immunosuppressive therapy refractory or relapsed severe aplastic anaemia. To investigate the response rate of hetrombopag combined with IST as first-line treatment, we designed a prospective pilot study including 32 patients with SAA treated with anti-human T lymphocyte porcine immunoglobulin (p-ATG), cyclosporine, and hetrombopag. In addition, 96 patients with SAA treated with p-ATG and cyclosporine alone were matched as controls. In total, 21.9% of patients treated with hetrombopag achieved complete response (CR) at 3 months, while 5.2% of patients achieved CR in the control group (P = 0.005). At 6 months, the CR rates were 34.4% in the hetrombopag group and 14.6% in the control group (P = 0.015). The overall response rates at 6 months were 68.7% and 50.0% in the hetrombopag and control groups, respectively. The median time to haematologic response was 56 days and 77 days, and to CR was 96 days and 214 days in the hetrombopag and control groups, respectively. In conclusion, adding hetrombopag to IST as first-line treatment resulted in faster and better haematologic response in SAA.

Nutritional Status as a Risk Factor for New-Onset Atrial Fibrillation in Acute Myocardial Infarction.

Purpose: Our study aimed to identify new-onset atrial fibrillation (NOAF) risk factors in acute myocardial infarction (AMI) patients after treatment with percutaneous coronary intervention (PCI) and investigate whether their nutritional status can be a predicting factor of NOAF. Patients and Methods: We analyzed 662 AMI patients after PCI for NOAF occurrence during follow-up hospitalization and divided them into an NOAF and non-NOAF group. The patients' nutritional status was assessed using the controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI). The Kaplan‒Meier analysis was used to assess NOAF-free survival in varying degrees of malnutrition. Cox proportional hazards models were used to identify the risk factors for NOAF. Results: Eighty-four (12.7%) patients developed NOAF during hospitalization. There was a statistically significant difference in the occurrence of NOAF among different categories of nutritional status. The CONUT score and GNRI classifications were independent predictors of NOAF. NOAF occurrence was associated with older age, higher uric acid levels, higher N-terminal pro-B-type natriuretic peptide levels, greater left atrial size, and worse Killip class upon admission. Conclusion: The nutritional status can affect NOAF occurrence in AMI patients after PCI. The CONUT score and GNRI are ideal tools for evaluating the nutritional status of AMI patients, with an excellent predictive effect on NOAF.

Antihuman T lymphocyte porcine immunoglobulin combined with cyclosporine as first-line immunosuppressive therapy for severe aplastic anemia in China: a large single-center, 10-year retrospective study.

Background: Antihuman T lymphocyte porcine immunoglobulin (p-ATG) has been the most common ATG preparation in immunosuppressive therapy (IST) in Chinese patients with severe aplastic anemia (SAA) since 2009. Objectives: This study aimed to evaluate the early hematologic response and long-term outcomes of a large cohort of patients with SAA who received p-ATG plus cyclosporine (CsA) as first-line therapy from 2010 to 2019. Design: This is a single-center retrospective study of medical records. Methods: We analyzed the data of 1023 consecutive patients with acquired aplastic anemia (AA) who underwent p-ATG combined with CsA as a first-line IST treatment from 2010 to 2019 at our department. Results: The median age of the patients was 24 (4-75) years, and the median follow-up time was 57.2 months (3 days-137.5 months). There was an early mortality rate of 2.8% with a median death time of 0.9 months (3 days-2.9 months). The overall response rates were 40.6% and 56.1% at 3 and 6 months, respectively. The 5-year cumulative incidences of relapse and clonal evolution were 9.0% [95% confidence interval (CI) = 4.2-16.0%] and 4.5% (95% CI = 1.4-10.6%), respectively. The 5-year overall survival (OS) and event-free survival rates were 83.7% (95% CI = 81.1-86.0%) and 50.4% (95% CI = 47.1-53.5%), respectively. Conclusion: p-ATG combined with CsA for the treatment of AA is effective and safe, and p-ATG can be used as an alternative ATG preparation for the standard IST regimen in areas in which h-ATG is not available.

Long-term outcomes of aplastic anemia with cytogenetic abnormalities at diagnosis.

OBJECTIVES: To elucidate the clinical characteristics of AA patients with cytogenetic abnormalities. METHODS: We retrospectively screened 30 patients (30/1206, 2.5%) with cytogenetic abnormalities from 1206 patients with severe and very severe AA who received immunosuppressive therapy (IST) during the years 2012-2019. RESULTS: The most common abnormalities were trisomy 8 (+8, 10/30, 33.3%) and loss of Y (-Y, 8/30, 26.7%). The abnormal clones disappeared 6 months after IST in 14 patients and sustained in 12 patients. Patients with sustained abnormal clones had a lower hematologic response at 6 months after IST than the disappeared (33.3% vs. 64.3%, p = .116). The hematologic response after IST, 5-year overall survival, 5-year event-free survival, myelodysplastic syndrome or acute myeloid leukemia transformation in AA patients with cytogenetic abnormalities were not statistically different from those in normal cytogenetic patients. CONCLUSION: For AA patients with chromosome abnormalities but ineligible for hematopoietic stem cell transplant, IST is effective and appropriate as first-line treatment.

Transient receptor potential vanilloid subtype 1: A potential therapeutic target for fibrotic diseases.

The transient receptor potential vanilloid subtype 1 (TRPV1), belonging to the TRPV channel family, is a non-selective, calcium-dependent, cation channel implicated in several pathophysiological processes. Collagen, an extracellular matrix component, can accumulate under pathological conditions and may lead to the destruction of tissue structure, organ dysfunction, and organ failure. Increasing evidence indicates that TRPV1 plays a role in the development and occurrence of fibrotic diseases, including myocardial, renal, pancreatic, and corneal fibrosis. However, the mechanism by which TRPV1 regulates fibrosis remains unclear. This review highlights the comprehensive role played by TRPV1 in regulating pro-fibrotic processes, the potential of TRPV1 as a therapeutic target in fibrotic diseases, as well as the different signaling pathways associated with TRPV1 and fibrosis.

First-line immunosuppressive therapy with rATG and CsA for severe aplastic anemia: 15 years' experience.

Rabbit antithymocyte globulin (rATG) instead of horse ATG has been used for severe aplastic anemia (SAA) patients in China. This study aimed to investigate the hematologic responses and long-term overall survival (OS) outcomes in SAA patients who received rATG and cyclosporine as first-line immunosuppressive therapy. We analyzed data of 542 SAA patients treated with this therapy between 2005 and 2019. The median age was 20 (range, 2-80) years, and the median follow-up time was 45.5 (range, 0.1-191.4) months. The early mortality rate was 3.9%. The overall response rates (ORRs) were 40.2%, 56.1%, and 62.4% at 3, 6, and 12 months, respectively. The 6- and 12-month ORR of patients treated with 3 mg/kg/d of rATG in 2015-2019 seemed higher than that of patients treated with 3.5-3.75 mg/kg/day in 2005-2014 (60.2% vs. 54.9%, P = 0.30 and 69.9% vs. 60.1%, P = 0.049, respectively). The 10-year cumulative incidences of relapse and clonal evolution were 10.6 ± 2.9% and 7.5 ± 1.5%, respectively. The 10-year OS rate and event-free survival rate were 80.1 ± 2.1% and 75.6 ± 3.7%, respectively. Age, disease severity, treatment periods, and the interval from diagnosis to IST were independent predictors of OS. In conclusion, 3 mg/kg/day rATG is effective as first-line treatment for SAA.

A multicenter phase II study on the efficacy and safety of hetrombopag in patients with severe aplastic anemia refractory to immunosuppressive therapy.

Background: In this single-arm phase II study (NCT03557099), we evaluated the efficacy and safety of hetrombopag, a small molecule thrombopoietin (TPO) receptor agonist, in patients with severe aplastic anemia (SAA) who were refractory to standard first-line immunosuppressive therapy (IST). Methods: SAA patients who were refractory to standard first-line IST were given hetrombopag orally at an initial dose of 7.5 mg once daily to a maximum of 15 mg once daily, for a total of 52 weeks. The primary endpoint was proportion of patients achieving hematologic responses in ⩾1 lineage at week 18. Results: A total of 55 eligible patients were enrolled and received hetrombopag treatment. This study met its primary endpoint, with 23 [41.8%, 95% confidence interval (CI) = 28.7-55.9] patients achieving hematologic response in ⩾1 lineage at week 18 after initiation of hetrombopag treatment. Twenty-four (43.6%, 95% CI = 30.3-57.7) and 27 (49.1%, 95% CI = 35.4-62.9) of the 55 patients responded in ⩾1 lineage at weeks 24 and 52, respectively. Median time to initial hematologic response was 7.9 weeks (range = 2.0-32.1). The responses were durable, with a 12-month relapse-free survival rate of 82.2% (95% CI = 62.2-92.2). Adverse events occurred in 54 (98.2%) patients, and 28 (50.9%) patients had treatment-related adverse events. Seventeen (30.9%) patients had adverse events of grade ⩾3. Serious adverse events occurred in 15 (27.3%) patients and three deaths (5.5%) were reported. Conclusion: Hetrombopag showed encouraging efficacy with durable hematologic responses in patients with SAA who were refractory to IST. Hetrombopag was well tolerant and safe for long-term use. ClinicalTrialsgov identifier: NCT03557099.

Efficacy of eltrombopag with immunosuppressive therapy for children with acquired aplastic anemia.

Background: Eltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial. Methods: We performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) by propensity score matching (PSM). Results: There was no difference in the overall response (OR) rate between the EPAG group and IST group (53.3% vs. 46.7% at 3 months, P = 0.655; 66.7% vs. 57.8% at 6 months, P = 0.543), but the complete response (CR) rate was statistically significant (20.0% vs. 4.4% at 3 months, P = 0.094; 46.7% vs. 13.3% at 6 months, P = 0.012). The median time to achieve a hematological response in the EPAG and IST groups was 105 days and 184 days, respectively. No difference was observed in the event-free survival (EFS) or overall survival (OS) rates. Conclusion: Adding EPAG to standard IST as the first-line treatment for children with acquired SAA improved the rapidity of hematological response and the CR rate but did not improve the OR or EFS rates.

Comparison of Levitt's CO breath test and the 15 N-glycine labeling technique for measuring the lifespan of human red blood cells.

The red blood cell (RBC) lifespan is an important physiological indicator of clear significance in clinical research, used for the differential diagnosis of various diseases such as anemia, compensatory phase hemolysis, and polycythemia. The 15 N-glycine labeling technique is the gold standard method for determining RBC lifespans. However, the usefulness of this technique in clinical settings is seriously hindered by the several weeks required to complete the analyses. Levitt's CO breath test is another reliable technique for determining RBC lifespans, with a simpler protocol giving much faster results, making it more useful in clinical applications. We compared the CO breath test and 15 N-glycine labeling technique for measuring the human RBC lifespan. We investigated human RBC lifespans where each subject undertook both the 15 N-glycine labeling technique and the CO breath test. The correlation between the results from these two methods was analyzed. Eight of the ten subjects successfully completed the study. The RBC lifespan values obtained by Levitt's CO breath test were lower than those obtained by the 15 N-glycine labeling technique. The RBC lifespan values determined from the 15 N-glycine labeling technique and the CO breath test were significantly correlated, with a Pearson correlation coefficient of R = 0.98 (p < 0.05), while the R2 of the linear regression equation was 0.96. The CO breath test exhibits as good performance as the 15 N-glycine labelling technique in distinguishing healthy subjects from subjects with hemolysis. The result suggests that the CO breath test is a reliable method for quickly determining human RBC lifespans in clinical applications.

Time and residual hematopoiesis are crucial for PNH clones escape in hepatitis-associated aplastic anemia.

The presence of paroxysmal nocturnal hemoglobinuria (PNH) clones in aplastic anemia (AA) suggests immunopathogenesis, but when and how PNH clones emerge and proliferate are unclear. Hepatitis-associated aplastic anemia (HAAA) is a special variant of AA, contrarily to idiopathic AA, in HAAA the trigger for immune activation is clearer and represented by the hepatitis and thus serves as a good model for studying PNH clones. Ninety HAAA patients were enrolled, including 61 males and 29 females (median age 21 years). Four hundred three of idiopathic AA have been included as controls. The median time from hepatitis to cytopenia was 50 days (range 0-180 days) and from cytopenia to AA diagnosis was 26 days (range 2-370 days). PNH clones were detected in 8 HAAA patients (8.9%) at diagnosis and in 73 patients with idiopathic AA (IAA) (18.1%). PNH cells accounted for 4.2% (1.09-12.33%) of red cells and/or granulocytes and were more likely to be detected in patients with longer disease history and less severe disease. During follow-up, the cumulative incidence of PNH clones in HAAA increased to 18.9% (17/90). Nine HAAA patients newly developed PNH clones, including six immunosuppressive therapy (IST) nonresponders. The clone size was mostly stable during follow-up, and only 2 of 14 patients showed increased clone size without proof of hemolysis. In conclusion, PNH clones were infrequent in newly diagnosed HAAA, but their frequency increased to one that was similar to the IAA frequency during follow-up. These results suggest that the PNH clone selection/expansion process is dynamic and takes time to establish, confirming that retesting for PNH clones during follow-up is crucial.

[Relationship between Changes of Lymphocyte Subsets and Early Hematologic Response in Immunosuppressive Therapy of Severe Aplastic Anemia Patients].

OBJECTIVE: To explore the relationship between the change of lymphocyte subsets before and after immunosuppressive therapy (IST) with disease severity of severe aplastic anemia (SAA) and hematologic response to IST. METHODS: The clinical data of 94 patients with SAA/VSAA treated by r-ATG and CsA in our hospital from December 2009 to October 2011 was analyzed retrospectively. Among them, 26 patients who had sequential data of lymphocyte subsets and cytokines before and after treatment were enrolled. The relationship between lymphocyte subsets, cytokine level before IST and disease severity, as well as the relationship between changes if lymphocyte subsets, changes of cytokine and the HR after IST for 6 months was analyzed. RESULTS: There were no statistical differences in the ratio and absolute count of lymphocyte, the ratio and absolute count of each lymphocyte subsets, including CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, CD3-CD16+1CD56+NK cells, and CD19+B cells, and the level of cytokines, such as IL-1, IL-2, IL-4, IL-6 and TNF-α before IST between SAA and VSAA groups. Also, there were no statistical difference in the levels of above-motional parameter at 3 and 6 months after IST. The ratio and absolute count of Lym, absolute count of CD3+T cells, absolute count of B cells and IL-2 level in response group after IST for 3 and 6 months was significant lower than those before IST. However, only ratio of Lym showed significant decrease after IST for 3 and 6 months in non-response group. After IST for 3 months, the absolute count of CD3+T and CD4+T cells in response group was significant higher than those in non-response group. CONCLUSION: The hematopoietic recovery and early hematologic remission may be affected by the intensity of immune suppression reflected from the changes of lymphocyte subsets and the immune reconstruction reflected from the recovery of lymphocyte subsets. The immune reconstruction is most significant within 3 months after IST.

Eltrombopag, oral immunosuppressant and androgen combination therapy in twelve patients with refractory severe aplastic anemia.

Objective: Eltrombopag monotherapy or eltrombopag combined with immunosuppressant has achieved robust hematologic responses in severe aplastic anemia (SAA). In patients with refractory SAA, for whom hematopoietic stem cell transplantation is unavailable, we attempted to combine eltrombopag with oral immunosuppressant and androgen, to further improve hematologic response. Methods: We collected and analyzed data retrospectively from twelve refractory SAA cases who had received combination therapy of eltrombopag, oral immunosuppressant and androgen. All these patients had received intensive immunosuppressive treatment (IST) for more than 6 months and were evaluated as nonresponders. Results: A total of 12 SAA patients were treated with a combination of eltrombopag, an oral immunosuppressant (cyclosporine, N = 9; tacrolimus, N = 3) and androgen. The median maximum dose of eltrombopag was 75 mg/day (range, 75-150). After a median follow-up of 8.5 months (7-23), the overall response rate (ORR) was 42% (5/12, including trilineage, N = 4; hemoglobin + platelet, N = 1). Two of 5 responders reached normal blood counts. Optimal hematological response rates were reached at 6 months. The median increase in neutrophil, hemoglobin and platelet count were 1.64 × 109 /L (0.71-2.66), 53 g/L (25-66.5) and 25 × 109 /L (14-230), respectively. In general, the combination therapy was well tolerated; however, two patients suffered from non-lethal upper extremity venous thrombosis when they were platelet transfusion-dependent. Conclusion: Eltrombopag, oral immunosuppressant and androgen combination therapy in patients with IST-refractory SAA is feasible and could restore multi-lineage hematopoiesis. Thrombosis risk of eltrombopag still needs to be monitored.

Efficacy and safety of porcine ALG compared to rabbit ATG as first-line treatment for children with acquired aplastic anemia.

OBJECTIVE: To assess the outcomes of children with acquired aplastic anemia (AA) treated in China with first-line porcine anti-lymphocyte immunoglobulin (p-ALG)/rabbit anti-thymocyte immunoglobulin (r-ATG) combined with cyclosporine A (CSA). METHODS: We performed a single-center, non-randomized, retrospective cohort study to assess the outcomes of 189 children with AA treated in China with first-line p-ALG/r-ATG combined with CSA between 2014 and 2018. RESULTS: No significant differences were observed in the overall response rates at 3, 6, 12, or 24 months (3 months: 61.9% vs 67.4%, P = .5; 6 months: 70.9% vs 73.9%, P = .69; 12 months: 77.3% vs 73.3%, P = .58; 24 months: 81.6% vs 78.6%, P = .59) after either p-ALG- or r-ATG-based immunosuppressive therapy. No significant differences were observed in overall survival or failure-free survival between the p-ALG group and the r-ATG group. CONCLUSION: Our results reveal that the therapeutic efficacy and safety of p-ALG combined with CSA did not differ significantly from those of r-ATG combined with CSA as first-line therapy for pediatric patients with AA. Moreover, p-ALG has the advantage of significantly lower cost compared with r-ATG.

Next generation sequencing reveals co-existence of hereditary spherocytosis and Dubin-Johnson syndrome in a Chinese gril: A case report.

BACKGROUND: Hereditary spherocytosis (HS) is a hereditary disease of hemolytic anemia that occurs due to the erythrocyte membrane defects. Dubin-Johnson syndrome (DJS), which commonly results in jaundice, is a benign hereditary disorder of bilirubin clearance that occurs only rarely. The co-occurrence of HS and DJS is extremely rare. We recently diagnosed and treated a case of co-occurring HS and DJS. CASE SUMMARY: A 21-year-old female patient presented to our department because of severe jaundice, severe splenomegaly, and mild anemia since birth. We eventually confirmed the diagnosis of co-occurring DJS and HS by next generation sequencing (NGS). The treatment of ursodeoxycholic acid in combination with phenobarbital successfully increased hemoglobin and reduced total bilirubin and direct bilirubin. CONCLUSION: The routine application of NGS can efficiently render a definite diagnosis when inherited disorders are suspected.

Iron Deficiency in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Cross-Sectional Survey from a Single Institution in China.

BACKGROUND Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder that often manifests with chronic intravascular hemolysis. Iron deficiency in patients with PNH is most often due to urinary losses of iron secondary to chronic intravascular hemolysis. MATERIAL AND METHODS This cross-sectional survey assessed the prevalence of iron deficiency in a Chinese population of PNH patients who were enrolled between May 2012 and October 2014. RESULTS A total of 742 PNH cases were selected by FLARE and classified as classical PNH (15.36%), PNH in the setting of another specified bone marrow disorder (12.26%), and subclinical PNH (72.38%). The median age of all the patients was 32 years (range 5-77 years). The overall prevalence of iron deficiency was 17.9% among all the PNH patients enrolled in the survey, 76.3% (87/144) among those with classical PNH, 33.0% (30/91) among those with PNH in the setting of another specified bone marrow disorder, and 3.0% (16/537) among the subclinical PNH patients. The incidence of iron deficiency among classical PNH patients was higher than that in the other 2 subcategories (P-value=0.000). Multivariate analyses showed that age and disease duration were independent risk factors for iron deficiency in classical patients. CONCLUSIONS This survey shows that PNH patients were prone to iron deficiency, especially patients with classical PNH.

Moderate-dose cyclophosphamide in the treatment of relapsed/refractory T-cell large granular lymphocytic leukemia-associated pure red cell aplasia.

BACKGROUND: T-cell large granular lymphocyte leukemia (T-LGLL) is a rare disorder characterized by clonal proliferation of large granular lymphocytes (commonly CD3+/CD8+/CD57+). However, the available data regarding the optimal treatment for relapsed/refractory T-LGLL patients are limited. METHODS: We retrospectively reviewed 10 patients treated with immunosuppressive therapy consisting of intravenous moderate-dose cyclophosphamide (MD-CTX) together with oral cyclosporine A for relapsed/refractory T-LGLL in our hospital between July 2006 and March 2013. RESULTS: The overall response rate to MD-CTX was 60% (6/10; hematologic complete remission rate, 50%; hematologic partial remission rate, 10%). The median time to response was 28.5 days (range, 20-118 days). The relapse rate of MD-CTX was 50% (3/6); two of these three patients achieved hematologic complete remission after receiving a second course of MD-CTX. Neutropenia was the major adverse event of the MD-CTX regimen. The median time to neutropenia was 5.5 days (range, 1-10 days) and the median neutropenia duration was 5 days (range, 3-15 days). None of the patients developed severe infection. CONCLUSIONS: The MD-CTX regimen appears efficacious and safe in the treatment of relapsed/refractory T-LGLL patients.