Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes / 中华血液学杂志

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.

Hemophagocytic lymphohistiocytosis: presentation and outcome of twenty-one patients at a single institution

ABSTRACT Introduction: Hemophagocytic lymphohistiocytosis comprises a systemic hyperactivation of macrophages that requires prompt recognition of symptoms and early treatment. Objective and Method: In this context, we described clinical and laboratory characteristics, therapeutic modality and outcome of 21 patients with HLH treated at a pediatric oncology hospital between January 2000 and February 2019. Results: HLH mainly affected females, fever was the most frequent clinical sign and hyperferritinemia was the most prevalent laboratory abnormality. All patients were admitted to the intensive care unit (ICU) at some point. Fifteen (71.4%) patients presented resolution criteria and eight (53.3%) of them presented reactivation. The mortality rate was 57.1% and the mean time between diagnosis and death was 9.98 months. The 5-year overall survival (OS) was 36.7%. We observed a significant difference in prognosis associated with reactivation of HLH. These patients demonstrated an estimated 5-year OS of 25%, while all patients that did not reactivate were alive until the end of the follow-up. Conclusion: In conclusion, HLH is a rare disease with a high mortality rate, especially in patients with disease reactivation and those with familial- or immunodeficiency-associated forms, which makes early recognition and genetic testing crucial for appropriate management and prompt SCT indication.

A Case Report of Cyclic Thrombocytopenia with Periodic Anemia / 罕见病研究

Cyclic thrombocytopenia (CTP) is a rare hemorrhagic disorder characterized by cutaneous and mucosal bleeding and periodic fluctuations platelet count. The clinical characteristics and treatment response of a patient with CTP were analyzed. The patient is a 30-year-old male with recurrent cutaneous and mucosal bleeding for 5 years. Skin petechiae, oral blood blister, conjunctival hemorrhage, by tracing the history, monitoring changes in blood routine diagnosis of CTP, further testing of reticulocyte platelets and platelet hormone, and periodically promoting bone marrow megakaryocyte with changes of platelet, confirmed that the patient's periodic reduction in bone marrow hematopoiesis, was causing more damage. Periodic changes of reticulocyte, erythropoietin and erythroid hematopoiesis in bone marrow were also observed. The patient had normal Treg levels, no significant telomere length shortening in peripheral blood nucleated cells, and no clear pathogenic gene mutation was found by whole exon gene sequencing. Recombinant human thrombopoietin(rhTPO) treatment shortened the time of thrombocytopenia and increased the minimum platelet value. The average age of onset of CTP was 35 years old, some patients had severe bleeding, and more than half of the patients were misdiagnosed as primary immune thrombocytopenia. At present, the pathogenesis of CTP has not been clarified and there is no effective treatment. The experience of this patient suggests that rhTPO may be effective. This case of CTP complicated with periodic anemia is the first report. The exploration of its pathogenesis provides important information for understanding CTP.

Systematic analysis of cases of lymphoma with autoimmune hemocytopenia reported in the Chinese literature in the past 30 years / 中国肿瘤临床

The authors analyzed 140 cases of malignant lymphoma (ML) associated with autoimmune cytopenia (AIC), including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia (PRCA), and Evans syndrome. The analysis was based on cases reported in the literature as well as the reference lists of papers in this field from 1989 to 2019 by Chinese scholars. The number of cases involving various non-Hodgkin's lymphoma subtypes was small (n=1-28). Nevertheless, interesting and sometimes unexpected differences were noted among different types of ML and AIC. All types of AIC except AIN were seen to coexist with ML, and the increasing order of incidence was as follows: warm antibody-AIHA >ITP >cold antibody-AIHA>PRCA>Evans syndrome. CAS was only seen with B-cell lymphomas, WA-AIHA, and ITP, Evans syndrome was more frequent in B-cell lymphomas and PRCA predominantly occurred with T-cell lymphomas. Anti-lymphoma treatment seemed to be more effective against AIC than conventional therapy with steroids or immunoglobulin. Although based on a literature survey, this compilation of data indicates a complex relation between lymphoma and AIC and warrants more attention and specific studies.

Inmunodeficiencias primarias y citopenias / Primary immunodeficiencies and cytopenias

Introducción: La visión actual de las enfermedades por inmunodeficiencia primaria (IDP) incluye un número creciente de síndromes que están asociados con la desregulación inmune y la autoinmunidad como características predominantes. Las citopenias autoinmunes pueden ser el primer signo de desregulación que precede a la presentación clásica de inmunodeficiencia primaria, con infecciones recurrentes u oportunistas. El conocimiento de un espectro de enfermedades potencialmente involucradas (hematológicas, reumatológicas e inmunológicas) es crucial para la identificación de una cierta proporción de genotipos y fenotipos de otros diagnósticos descritos. También permitirá excluir desórdenes como lupus eritematoso sistémico, inmunodeficiencia variable común, síndrome linfoproliferativo autoinmune; así como realizar diagnósticos diferenciales noveles como la deficiencia de GATA2, deficiencia de CD27, deficiencia de sensibilidad a lipopolisacáridos, síndrome fosfoinositol-3-quinasa delta activada, inmunodeficiencia ligada a X con déficit de magnesio y otros. Objetivo: Proporcionar una sinopsis conceptual de la aparición de citopenias en las IDP con el propósito de actualizar el conocimiento actual sobre dicho tema y de aumentar la percepción, tanto de hematólogos como inmunólogos, en relación a la presentación de citopenias como manifestación de estas enfermedades. Métodos: Se revisaron artículos originales y de corte experimental publicados en la década 2009 - 2019, en algunas bases de datos de la Biblioteca Virtual de Salud (BVS) de Cuba. Conclusiones: Al igual que las formas benignas autolimitadas de citopenia autoimmune post o parainfecciosas, o la neutropenia autoimmune adquirida de la infancia, que generalmente ocurren independientemente de una IDP subyacente reconocida, muchas de las citopenias que acompañan a esta enfermedad (pero no todas) están mediadas por autoanticuerpos. Es esencial entonces, que los médicos valoren, ante la evidencia clara de citopenia, que esta puede ser autoinmune(AU)

Introduction: The current view of primary immunodeficiency diseases (IDP) includes an increasing number of syndromes that are associated with immune dysregulation and autoimmunity as predominant characteristics. Autoimmune cytopenias may be the first sign of dysregulation that precedes the classic presentation of primary immunodeficiency, with recurrent or opportunistic infections. The knowledge of a spectrum of potentially involved diseases (hematological, rheumatological and immunological) is crucial for the identification of a certain proportion of genotypes and phenotypes of other diagnoses described. It will also allow excluding disorders such as systemic lupus erythematosus, common variable immunodeficiency, autoimmune lymphoproliferative syndrome; as well as making novel differential diagnoses such as GATA2 deficiency, CD27 deficiency, lipopolysaccharide sensitivity deficiency, activated delta phosphoinositol-3-kinase syndrome, X-linked immunodeficiency with magnesium deficiency and others. Objective: This review provides a conceptual synopsis of the appearance of cytopenias in the IDPs with the purpose of updating current knowledge on this topic and increasing the perception, of both hematologists and immunologists, in relation to the presentation of cytopenias as manifestation of these diseases. Methodos: Original and experimental articles published in the 2009-2019 decade were reviewed in some databases of the Virtual Health Library (VHL) of Cuba. Conclusions: As the self-limited benign forms of post or parainfectious autoimmune cytopenia, or childhood acquired autoimmune neutropenia, which generally occur independently of a recognized underlying IDP, many of the cytopenias that accompany this disease (but not all) mediated by autoantibodies. It is essential, then, that doctors assess, given the clear evidence of cytopenia, that it may be autoimmune(AU)

Secondary hemophagocytic lymphohistiocytosis: a rare case report

Haemophagocytic lymphohistiocytosis (HLH) is a clinicopathologic syndrome, characterised by hyperinflammation due to inherited or acquired defects in the immune function, leading to unchecked proliferation of histiocytes and lymphocytes resulting in multiorgan dysfunction. HLH can be primary (familial) occurring in young children caused by underlying genetic defects in natural killer cells/cytotoxic T cells or secondary HLH occurring in older children or adults following infections, rheumatological disorders or malignancies.  HLH is a medical emergency, having varied clinical presentations and lacks a pathognomonic clinical or laboratory abnormality. Clinical presentations include unexplained fever, hepatomegaly, splenomegaly, skin rash, cytopenias, liver dysfunction, coagulation abnormality and neurological manifestations. It carries a poor prognosis. Early diagnosis based on HLH 2004 criteria and initiation of treatment is crucial in the management strategy, which is likely to improve the outcome of this life-threatening disease. The treatment strategies include immunosuppressive drugs, immunomodulatory therapy and autologous hematopoietic stem cell transplant in selected cases. Here with authors report a case of young adult, presenting with fever, thrombocytopenia, splenomegaly, and multi organ dysfunction, diagnosed as a case of secondary HLH based on the HLH 2004 guidelines.

Treatment of autoimmune hemolytic anemia: real world data from a reference center in Mexico

BACKGROUND: Warm autoimmune hemolytic anemia (w-AIHA) is an uncommon disease with heterogeneous response to treatment. Steroids are the standard treatment at diagnosis, whereas rituximab has recently been recommended as the second-line therapy of choice. Our main objective was to document the response to treatment in patients with newly diagnosed w-AIHA, including the effectiveness of low-dose rituximab as frontline treatment and for refractory disease. METHODS: Patients with w-AIHA from 2002 to 2017 were included. Relapse-free survival (RFS), probability of maintained response (MR), and time-to-response were analyzed using the Kaplan–Meier method. Response was classified as complete, partial, and no response. RESULTS: We included 64 adults with w-AIHA (39 women and 25 men). The median age was 37 (16–77) years. Response rates to steroids alone were 76.7%, rituximab plus steroids, 100%; and cyclophosphamide, 80%. RFS with steroids at 6, 36, and 72 months was 86.3%, 65.1%, and 59.7%, respectively. Eighteen patients received rituximab at 100 mg/wk for 4 weeks plus high-dose dexamethasone as first-line therapy, with RFS at 6, 36, and 72 months of 92.3%, 58.7% and 44.1%, respectively. Eight patients refractory to several lines of therapy were treated with low-dose rituximab, and all achieved a response (three complete response and five partial response) at a median 16 days (95% confidence interval, 14.1–17.8), with a 75% probability of MR at 103 months; the mean MR was 81.93±18 months. CONCLUSION: Outcomes of w-AIHA treatment were considerably heterogeneous. Low rituximab doses plus high dexamethasone doses were effective for refractory disease.

Clinical Diagnosis and Treatment Recommendations for Immune Checkpoint Inhibitor-related Hematological Adverse Events / 中国肺癌杂志

Immune checkpoint inhibitors are able to reactivate the immune system therefore enhance the anti-tumor effects. However, over-activated T cells may induce immune related adverse events (irAEs). Hematological irAEs are rarely reported, which mainly represent as mono-lineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even lethal, such as hemophagocytic lymphohistiocytosis. The clinical manifestations of hematological irAEs will be summarized and recommendations of diagnosis and treatment are proposed.

A Case Report of Successful Treatment with Kamikihito and Kyukikyogaito for Refractory Cytopenia of Childhood / 日本東洋医学雑誌

An eight-year-old girl was referred and admitted to our hospital with the chief complaint of purpura on her lower legs. Blood tests revealed pancytopenia, and bone marrow findings showed marrow hypoplasia. Refractory cytopenia of childhood (RCC) was diagnosed based on the central diagnostic system of the Myelodysplastic Syndrome Committee of the Japanese Society of Pediatric Hematology. Immunosuppressive therapy was performed with the administration of rabbit antithymocyte globulin, methylprednisolone and cyclosporin A,but it was not effective. Eight months after admission to our hospital, Kampo treatment was started based on traditional Kampo diagnosis. After treatment with oral administration of kamikihito and kyukikyogaito, her pancytopenia gradually improved. Erythrocyte transfusion was discontinued after 2 months, and concentrated platelet transfusion also became unnecessary after 3 months. As a result of improvement in pancytopenia, her white blood cell count, hemoglobin value, and platelet count reached almost normal levels after 16 months. The scheduled bone marrow transplantation was canceled. The action mechanisms of kamikihito and kyukikyogaito for RCC are not clear, and their effective rates are also unknown. However, Kampo treatments are less invasive, inexpensive, and have few side effects. We believe that Kampo medicine is a therapeutic method that should be actively attempted in cases of RCC with poor response to standard treatment.

Current opinions on refractory cytopenia of childhood / 国际儿科学杂志

Myelodysplastic syndromes are a group of malignant myeloid clonal diseases that originate from hematopoietic stem/progenitor cells.They are characterized by decreased peripheral blood cells,dysplasia of one or multiple lineages of myeloid hematopoietic cells,and prone to transform into acute myeloid leukemia.Refractory cytopenia of childhood is the most common clinical type of MDS in children.Its clinical manifestations include the decrease in one or multiple lineages of peripheral blood cells,abnormal development of the myeloid lineage,and the absence of excess blasts.This type was first introduced in WHO children's MDS in 2008.Considering the low incidence and lack of specific diagnostic methods,difficulty in early diagnosis and poor prognosis of RCC,we summarize the definition,clinical manifestations,laboratory tests,diagnosis and differential diagnosis,and treatment strategies of RCC in this review.

Pathogeny and treatment of cirrhotic portal hypertension complicated by peripheral blood cytope-nia / 临床外科杂志

There are three causes of cirrhotic portal hypertension(CPH)complicated by peripher-al blood cytopenia:splenic factors(about 80%),non-splenic factors(about 4%)and comprehensive fac-tors(about 16%).The treatment includes non-surgical treatment and surgical treatment.Mild to moderate peripheral blood cell reduction is suitable for non-surgical treatment.Severe peripheral blood cytopenia is feasible to surgical treatment.Splenic factors are the main cause of peripheral cytopenia in CPH,but not all;The treatment method should be based on the degree of peripheral blood cytopenia.

Peripheral cytopenia and its contituent ratio in cirrhotic portal hypertension / 中华普通外科杂志

Objective To investigate the causes of peripheral cytopenia in patients with posthepatitic cirrhosis and portal hypertensive splenomegaly.Methods The clinical data of 183 patients with hepatitic cirrhosis and portal hypertensive splenomegaly complicated by peripheral cytopenia who were operated in our hospital in the past 17 years were retrospectively studied.Results All these patients underwent splenectomy.Before operation,all these patients had one or more types of peripheral cytopenia (cumulative cytopenia:390 patient-times).After splenectomy,blood counts in 79.2％ returned to normal;in 15.9％ increased but failed to reach normal levels;and in 4.9％ became lower than before operation.5 patients died soon after operation.Conclusion Hypersplenism is the main cause for the peripheral cytopenia most cirrhotic portal hypertension patients.Splenectormy is an effective method to treat hypersplenism.

Three Cases of Cytopenia during Azathioprine Treatment for Bullous Disease / 대한피부과학회지

Azathioprine is an immunosuppressive drug that has been widely used in dermatology for the treatment of immunobullous diseases. Myelosuppression is the most important side effect and requires close observation of the complete blood cell count. The clinical findings of myelosuppression include general weakness, poor oral intake, nausea, dyspnea, and pallor. It can occur within several weeks to years after initial azathioprine treatment; thus, a weekly full blood count for the first 4 weeks, followed by reduced frequency of monitoring to a minimum of once every 3 months is recommended. If the myelosuppression is not treated properly, it can lead to fever, secondary infection, sepsis, and even death. Herein, we present three educational cases for dermatologists to order to underline the risk of myelosuppression during azathioprine treatment.

Treatment and response of autoimmune cytopenia occurring after allogeneic hematopoietic cell transplantation in children

BACKGROUND: Autoimmune cytopenia (AIC) is a rare complication of allogeneic hematopoietic cell transplantation (HCT). In this study, we reviewed the diagnosis, treatment and response to therapy for pediatric patients with post-HCT AIC at our institution. METHODS: Of the 292 allogeneic HCTs performed from January, 2011 to December, 2015 at the Department of Pediatrics, The Catholic University of Korea, seven were complicated by post-HCT AIC, resulting in an incidence of 2.4%. RESULTS: All seven patients with post-HCT AIC had received unrelated donor transplant. Six of seven patients had a major donor-recipient blood type mismatch. The subtypes of AIC were as follows: immune thrombocytopenia (ITP) 2, autoimmune hemolytic anemia (AIHA) 2, Evans syndrome 3. Median time from HCT to AIC diagnosis was 3.6 months. All but one patient responded to first line therapy of steroid±intravenous immunoglobulin (IVIG), but none achieved complete response (CR) with this treatment. After a median duration of treatment of 15.3 months, two patients with ITP achieved CR and five had partial response (PR) of AIC. Five patients were treated with rituximab, resulting in the following response: 2 CR, 2 PR, 1 no response (NR). Median time to response to rituximab was 26 days from first infusion. All patients are alive without event. CONCLUSION: Post-HCT AIC is a rare complication that may not resolve despite prolonged therapy. Rapid initiation of second line agents including but not limited to B cell depleting treatment should be considered for those that fail to achieve CR with first line therapy.

A Case of Myelodysplastic Syndrome Characterized by Hemolytic Anemia at Presentation

A man aged 78 yr with no history of chemotherapy or toxic exposure presented with a history of dyspnea and intermittent red urine for 3 months and several years, respectively. Hematologic data at admission were as follows: hemoglobin, 65 g/L; white blood cell count, 4.05x109/L; platelet count, 96x109/L; and reticulocyte count, 10.9%. A peripheral blood smear revealed polychromasia, nucleated red blood cells, and neutrophils with a non-lobulated nucleus. The bone marrow was hypercellular and exhibited an increase in erythroid precursors with trilineage dysplasia and our findings were suggestive of refractory cytopenia with multilineage dysplasia (RCMD). Karyotype of bone marrow cells was as follows: 45,XY,der(9;17)(p10;q10),add(18)(q11.2)[10]/45,idem,del(3)(q21)[10]. Other laboratory findings showed decreased serum haptoglobin, increased lactate dehydrogenase, and increased indirect bilirubin levels. Moreover, results of the direct/indirect antiglobulin test (Coombs' test) and paroxysmal nocturnal hemoglobinuria analysis with CD55, CD59, fluorescent aerolysin (FLAER), and CD24 were negative. Cold agglutinin and Donath-Landsteiner antibodies were not detected. This is a case of myelodysplastic syndrome (MDS) associated with hemolytic anemia and complex chromosomal abnormalities at presentation.

Expression and significance of chemokine receptors CXCR3, CCR5 and CCR3 in the spleen tissues of rats with cirrhosis and hypersplenism / 中华消化外科杂志

Objective To investigate the expressions of T helper cell 1 (Th1)-associated chemokine receptors CXCR3, CCR5 and T helper cell 2 (Th2)-associated chemokine receptor CCR3 in the spleen tissues of rats with cirrhosis and hypersplenism and probe into the balance between Th1/Th2 lymphocyte subsets.Methods Experimental study was adopted.Forty-six male SD rats were randomized into the hypersplenic group (n =36) and the control group (n =10).In the hypersplenic group, the rats were fed with 40％ CCl4 peanut oil solution (3.0 mL/kg, twice per week) and 15％ white spirit for 8 weeks to build the hypersplenic model.The rats in the control group received normal feeding.The animal models with cirrhosis and hypersplenism were confirmed by liver function test, routine blood test, HE staining and Masson staining after visual inspection.The expressions of chemokine receptors of CXCR3, CCR5 and CCR3 were detected by immunohistochemical staining and Western blot.Measurement data with normal distribution were presented as x ± s.Comparison between groups was done using the independent sample t test.Results Results of visual inspection: the rats in the hypersplenic group suffered from severe hair-shedding, metal fatigue and inappetence, with hair dimming and inactivity.There were rats dead successively 5 weeks after model establishment and 19 rats finally survived.The rats in the control group had color and gloss hair, with good appetite and spirits.They were active and sensitive to external stimulation.Changes of pathological morphology in liver: in the hypersplenic group, the fibers became denser and disordered, making normal structure of liver tissues destroyed.The hepatic lobules separated by fibrous bundle and proliferative hepatic cell mass were segmented and surrounded by thick fibrous,leading to the formation of pseudolobule.Disorganized hepatocytes suffused adipocytes, the nucleus of heterocysts enlarged or even multinucleated cells appeared.There was no change in the control group.Changes of pathological morphology in spleen: the rats in the hypersplenic group had slightly swelling spleen with the areas of red pulp increased and whit pulp disappeared gradually.Vascular endothelium became thicker and proliferated.Thickened central artery and fibrosis were depicted.Splenic sinusoid extended.There was no change of spleen tissues in the control group.Changes of liver function : the levels of ALT and AST of rats were (264 ± 111) U/L and (687 ± 299) U/L in the hypersplenic group,which were significantly different from (27 ± 8)U/L and (124 ± 20)U/L in the control group (t =5.64, 4.98,P ＜ 0.05).The level of total protein was (54 ± 8)g/L in the hypersplenic group, which was significantly different from (65 ± 3)g/L in the control group (t =-3.35, P ＜ 0.05).Changes of peripheral blood cell count: the white blood cell (WBC) count in the hypersplenic group was (23.9 ± 5.0) × 109/L, which was significantly different from (6.2 ± 2.4) × 109/L in the control group (t =3.50, P ＜ 0.05).The red blood cell count and platelet count in the hypersplenic group were (6.3 ±0.7) × 1012/L and (418 ± 124) × 109/L, which were significantly different from (8.0 ± 0.6) × 1012/L and (1 109 ± 161) × 109/L in the control group (t =-2.28,-4.92, P ＜ 0.05).Results of immunohistochemical staining: the cytomembrane and/or cytoplasm stained yellow, brown or sepia were defined as positive performance of CXCR3, CCR5 and CCR3.The absorbance A values of CXCR3 and CCR5 were (81.7 ±24.4) × 10-3 and (3.6 ± 1.3) × 10-3 in the hypersplenic group, which were significantly different from (19.2 ± 5.8) × 10-3 and (1.2 ± 0.4) × 10-3 in the control group (t =16.22, 9.09, P ＜ 0.05).The absorbance A value of CCR3 was (8.8 ±3.7) × 10-3 in the hypersplenic group and (7.9 ±2.8) × 10-3 in the control group, respectively, showing no significant difference between the 2 groups (t =0.87, P ＞ 0.05).The rates of positive cells of CXCR3 and CCR5 was 52％ ± 9％ and 19％ ± 5％ in the hypersplenic group, which were significantly different from 21％±5％ and 10％±3％ in the control group (t =17.31, 8.21, P ＜0.05).The rates of positive cells of CCR3 in the hypersplenic group and control group were 35％ ± 9％ and 33％ ± 14％, respectively, showing no significant difference between the 2 groups (t =0.43, P ＞ 0.05).Results of Western blot test : the relative expressions of CXCR3 and CCR5 were 2.45 ± 0.85 and 0.94 ± 0.48 in the hypersplenic group, which were significantly different from 1.31 ± 0.95 and 0.32 ± 0.26 in the control group (t =2.62, 2.91, P ＜ 0.05).The relative expression of CCR3 was 0.47 ± 0.27 in the hypersplenic group, which was significantly different from 0.92 ± 0.67 in the control group (t =-2.18, P ＜ 0.05).Conclusion The abnormal expression of chemokine receptors in the spleen tissues of rats with cirrhosis and hypersplenism induced by CCl4 suggests that functional imbalance of Th1/Th2 lymphocyte subsets may play an important role in the regulation of peripheral blood cytopenia.

A Unique Case of Erdheim-Chester Disease with Axial Skeleton, Lymph Node, and Bone Marrow Involvement / Journal of the Korean Cancer Association, 대한암학회지

Erdheim-Chester disease is a rare non-Langerhans-cell histiocytosis with bone and organ involvement. A 76-year-old man presented with low back pain and a history of visits for exertional dyspnea. We diagnosed him with anemia of chronic disease, cytopenia related to chronic illness, chronic renal failure due to hypertension, and hypothyroidism. However, we could not determine a definite cause or explanation for the cytopenia. Multiple osteosclerotic axial skeleton lesions and axillary lymph node enlargement were detected by computed tomography. Bone marrow biopsy revealed histiocytic infiltration, which was CD68-positive and CD1a-negative. This report describes an unusual presentation of Erdheim-Chester disease involving the bone marrow, axial skeleton, and lymph nodes.

Bone marrow changes in elderly.

Aim: To study the bone marrow changes in elderly patients (above 60 years of age). Material and methods: Bone marrow records from the pathology laboratory in the Department of Pathology, Bangalore Medical College, Bangalore, from March 2012 to june 2013, were searched, and cases from all patients at least 60 years old at the time of bone marrow study were retrospectively reviewed. Results: During the 16 months period, 164 bone marrow examinations were performed, andout of these, 50 patients were at least 60 years old. The age range of the patients was 60 to 82 years , 27 were males and 23 were females. 47 cases (94%) yielded specific diagnosis. 27 cases (54%) had nutritional anemia, 6 cases (12%) were diagnosed as myeloma, 3 cases (6%) had aplastic anemia, 3 cases (6%) had chronic lymphocytic leukemia/ small lymphocytic leukemia infiltrating the bone marrow; 2 cases (4%) had acute myeloid leukemia, 2 myelofibrosis - grade 3, 2 cases were diagnosed to have monoclonal gammopathy of undetermined significance (4%), 1 case (2%) had metastatic deposits from prostatic carcinoma and 1 case (2%) of mylodysplastic syndrome - refractory cytopenia with multi lineage dysplasia and ringed sideroblasts was diagnosed. Conclusions: In this study we found that after nutritional anemia, plasma cell dyscrasias were the most common findings in bone marrow studies in elderly patients. Diagnosis of plasma cell dyscrasias prompt for early institution of treatment resulting in reduced morbidity and mortality in such patients.

Stady on the clinical characteristics of 10 patients with idiopathic cytopenia of undetermined significance / 重庆医学

Objective To analyze the clinical and pathologic features in patients with ldiopathic cytopenia of undetermined signif-icance (ICUS) ,and provide the diagnostic basis .Methods 10 ICUS patients who did not fulfil minimal diagnostic criteria for MDS but suffered from constant (>6 months) progressive cytopenia ,with no marked dysplasia (<10% in three-major cell lineages) and abnormal karyotype were reported .Results 2 of 10 patients transited to MDS ,bone marrow review showed that ≥2 cells appeared diagnostic pathology development .Karyotype analysis showed that 1 case was still normal ,1 case lost a normal chromosome 20 (20q-) ,the rest 8 cases had been efollowed up for 6 to 25 months and still maintain ICUS .Conclusion Patients with MDS who fail to meet the diagnostic criteria of ICUS ,must carry out regular follow-up .There are some patients can transition to public MDS after a certain incubation period ,in fact it is Pre-MDS or MDS-early before ,which shows that ICUS should cause clinical attention ,so that avoid missed diagnosis .

A Primary Care Approach to Myelodysplastic Syndromes / 가정의학회지

Myelodysplastic syndromes (MDS) are probably the most common hematologic malignancies in adults over the age of 60 and are a major source of morbidity and mortality among older age groups. Diagnosis and management of this chronic blood cancer has evolved significantly in recent years and there are Food and Drug Administration-approved therapies that can extend patients' life expectancy and improve quality of life. Primary care physicians (PCPs) are often involved in the process of diagnosis and follow-up of MDS patients, especially those in low-risk groups. They can therefore play an important role in improving patient care and quality of life by ensuring early referral and participating in supportive management. There is also a shortage of oncologists which increases the importance of the role of PCPs in management of MDS patients. In the face of limited resources, PCPs can improve access and quality of care in MDS patients. This article provides an overview of the common manifestations, diagnostic approaches, and therapeutic modalities of MDS for PCPs, with a focus on when to suspect MDS, when a referral is appropriate, and how to provide appropriate supportive care for patients diagnosed with MDS.