Bone Marrow Hyperplasia Research Articles

PB1990 THE CHANGE OF BONE MARROW MICROENVIRONMENT OF SECONDARY POOR GRAFT FUNCTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION AND ITS EFFECT ON PROGNOSIS

Background:Secondary poor graft functionis a serious life‐threatening complication after allogeneic hematopoietic stem cell transplantation, which pathogenesis, evolution and prognosis are still unclear.Aims:To explore the role of adhesion related indicators in secondary poor graft functionafter allogeneic hematopoietic stem cell transplantationMethods:In this study, clinical data and post‐transplantation status of 106 patients with hematological tumour who were enrolled in our center and underwent allo‐HSCT from Jan. 1, 2016 to Jan. 31, 2017 was counted.The patients were divided into good graft function (GGF) group and secondary poor graft function (sPGF) group according to the implantation status after transplantation. The differences of age, primary disease, stem cell source, HLA matching, sex matching, ABO blood group matching, degree of bone marrow hyperplasia before transplantation, recurrence rate and mortality between the two groups were compared.29 patients with sPGF after transplantation were selected as the experimental group while 29 patients with GGF were selected as the control group.Results:The changes of adhesion related indicators in the two groups were detected.There were no significant differences in age, primary disease, stem cell origin, HLA matching, sex matching, ABO blood group matching and the degree of bone marrow proliferation before transplantation between the two groups (P > 0.05). The infection rate of CMV in sPGF group was significantly higher than that in GGF group, and the remission rate before transplantation in sPGF group was significantly lower than that in GGF group (P < 0.05).Cox regression analysis showed that the survival rate of patients with sPGF after allo‐HSCT was significantly lower than that of patients without sPGF (P < 0.05, HR = 3.598).The expression of CD44, CD29, ICAM‐1 and VCAM‐1 in sPGF group was not significantly different from that in control group (P > 0.05), but the expression of CD105 was higher than that in control group, and the expression of Cx43 was lower than that in control group (P < 0.05).Summary/Conclusion:We believe that the survival rate of patients with sPGF after allo‐HSCT will decrease significantly, and the occurrence of sPGF after transplantation may be related to the increase of CD105 expression and the decrease of Cx43 expression in bone marrow stromal cells before transplantation.

Establishment of 137Cs γ ray Combined with Cyclophosphamide and Chloramphenicol-Mediated Mouse Model of Acquired Aplastic Anemia

To improve and establish the mouse model with aplastic anemia (AA) mediated by 137Cs γ-ray irradiation combined with cyclophosphamide (CTX) and chloramphenicol (CHL) injection,so as to provide a stable model for studying the pathogenesis and treatment of AA . The BALB/c mice were exposed to 137Cs γ-ray of 3-5 Gy(91 cGy/min) and were intraperitoneally injected with CTX of 25 mg/(kg.d) and CHL of 62.5 mg/(kg.d) at D 4,5 and 6 after irradiation; the WBC, platelet and reticulocyte counts in peripheral blood as well as the mucleated cell count in bone marrow and bone marrow smears were detected . The 3-lineage cells in peripheral blood of BALB/c mouse model with acquired AA were rapidly reduced, especially WBC, platelet and reticulocyte counts were lowest at D 14,the 3-lineage cells in peripheral blood were still severely reduced at D 28; the nucleated cell count in bone marrow significantly dcreased,the bone marrow hyperplasia was reduced or severely reduced; the pathological sections of bone marrow showed the severe reduction of hematopoietic cells and the increased of non-hematopoietic cells such as fat cells. The mouse model with acquired AA has been established by 137Cs γ-ray irradiation combined with CTX and CHL injection. All detection indicators of this model reach to diagnostic criteria for acquired AA,therefore this mouse model may be used as the model for study of pathogenesis and treatment of acquired AA.

Regulation of Red Blood Cell Volume with Exercise Training.

Hypervolemia is a hallmark of endurance training (ET) and manifests by similar elevations in plasma (PV) and red blood cell volume (RBCV) so that hematocrit largely remains unaltered following weeks/months of training. While the mechanisms facilitating PV expansion with ET have been previously reviewed extensively this is not the case for RBCV. Endurance champions may have 40% more RBCV than controls and RBCV may increase up to 10% following months of regular exercise training in healthy individuals. Such adaptations are the main factor leading to concomitant changes in maximal oxygen uptake. The increase in RBCV is preceded by that of PV after few ET sessions, which in turn transiently decreases the hematocrit. The "critmeter" theory suggests that O2 sensors located within the juxtamedullary apparatus regulate the hematocrit via modulation of renal erythropoietin (EPO) production according to arterial O2 content-dependent changes in tissue O2 pressure. Hence, the initial decrease in hematocrit can be considered as a primary mechanism facilitating RBCV expansion with ET. Furthermore, after a single endurance exercise bout blood volume-regulating hormones ANGII and VPN increase transiently. Both stimulate renal EPO production. Catecholamines and cortisol, stress hormones acutely increased by endurance exercise, may facilitate the release of red blood cells from the bone marrow, thus possibly contributing to ET-induced erythropoiesis. These and other endocrine effects could be enhanced by the hyperplasia of the hematopoietic bone marrow observed in endurance athletes. © 2019 American Physiological Society. Compr Physiol 9:149-164, 2019.

Phenylhydrazine and its salts – calculated on phenylhydrazine. Documentation of proposed values of occupational exposure limits (OELs)

Phenylhydrazine and its salts – calculated on phenylhydrazine. Documentation of proposed values of occupational exposure limits (OELs)

Retraction: Disruption of the NAD(P)H:Quinone Oxidoreductase 1 (NQO1) Gene in Mice Causes Myelogenous Hyperplasia.

NAD(P)H:quinone oxidoreductase1 (NQO1) is a cytosolic protein that reduces and detoxifies quinones and their derivatives, thus protecting cells against redox cycling and oxidative stress. Disruption of the NQO1 gene in mice caused myeloid hyperplasia of bone marrow and highly significant increases in blood neutrophils, eosinophils, and basophils. NQO1-null mice also showed a decrease in lymphocytes and WBCs as compared with wild-type mice. Various techniques also demonstrated an increase in megakaryocytes without an increase in blood platelets. Histological analysis of liver, kidney, spleen, and thymus did not demonstrate a difference between wild-type and NQO1-null mice or a sign of infection. Blood cultures and urine analysis also did not demonstrate any sign of infection in NQO1-null and wild-type mice. Additional analysis of the bone marrow from NQO1-null mice revealed that loss of NQO1 alters the intracellular redox status because of accumulation of NAD(P)H, cofactors for NQO1. This causes a reduction in the levels of pyridine nucleotides and tumor suppressor proteins p53 and p73, and a decrease in apoptosis. The decrease in apoptosis causes myelogenous hyperplasia in NQO1-null mice. These results demonstrate that NQO1 acts as an endogenous factor in the protection against myelogenous hyperplasia. This is significant because 2-4% of human individuals without known abnormalities, and >25% of individuals with benzene poisoning and acute myelogenic leukemia are homozygous for a mutant allele (P187S) of NQO1 and lack NQO1 protein/activity.

Clinical analysis of blastic plasmacytoid dendritic cell neoplasm

Objective To investigate the clinical features, diagnosis, treatment and efficacy of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in order to improve the understanding of BPDCN. Methods On 21 August 2017, a case of BPDCN patient admitted in Hematology Department of Beijing Tsinghua Changgung Hospital affiliated to Tsinghua University, was included in this study. This patient was diagnosed as BPDCN in other hospital in November 2016, and then received 5 courses of CHOP (cyclophosphamide+ doxorubicin+ vincristine+ prednisone)-21 regimen for chemotherapy. After partial remission (PR), the patient relapsed in June 2017, and was admitted in Hematology Department of our hospital for further treatment. After admission, combined with the patient′s medical history, diagnosis was made according to the clinical manifestations, bone marrow examination and relevant laboratory examination results. On 25 August 2017, the patient received 3 courses of VDCP (vindesine+ daunorubicin+ cyclophosphamide+ dexamethasone) regimen for chemotherapy. Vindesine 4 mg/d, d1, 8, 15, 22; doxorubicin 60 mg/d, d4-5, 80 mg/d, d6, 60 mg/d, d15-16; cyclophosphamide 1.7 g/d, d4, 15; and dexamethasone 17 mg/d, d1-7 were applied. The laboratory test results, further diagnosis and assesement of disease, and curative effects of this patient were analyzed retrospectively, and related literature was reviewed to explore the research progress of BPDCN diagnosis and treatment. Results ① After admission, flow cytometry test results of the patients′ bone marrow cells showed abnormal cell population within original cell distribution area, accounting for about 9.4%. Abnormal cell expressed human leukocyte antigen (HLA)-DR, CD4, CD38, CD56 and CD123, and some expressed CD33. Results of morphological examination of bone marrow cells showed that proliferation of bone marrow cells was significantly active. Proportion of granulocyte was 38.0%, proportion of erythroid was 24.0%, and ratio of granulocyte and erythroid was 1.58∶1. Megakaryotic cells and heteromorphic lymphoid cells could be seen. Ratio of primitive cells was 27.0%, and was BPDCN bone marrow invasion. Bone marrow cell immunohistochemical test results showed CD4 (+ ), CD56 (+ ), CD123 (+ ), CD68 (+ ), CD235 (erythroid+ ), myeloperoxidase (MPO) (granulocyte+ ), terminal deoxynucleotidyl transferase (TdT) (-), CD117 (<1%), CD3 (-), CD20 (-), CD23 (-), T cell intracellular antigen (TIA)-1 (+ ), granzyme B (-). Results of scalp biopsy showed that tumor cells were diffuse in dermal layer of the skin without involving the epidermis. Immunohistochemical results showed that CD4 (+ ), CD43 (+ ), CD56 (+ ), CD123 (weak+ ), TdT (scattered+ ), CD117 (-), CD3 (-), CD23 (-), TIA-1 (-), granzyme B (-), and CD68 (scattered+ ). ② The patient was diagnosed with BPDCN, and was comprehensively evaluated as progressive disease (PD) at admission. ③ After the treatment with VDCP regimen, all rashes on the scalp, face and trunk of the patient were eliminated. The granulocyte count returned to the normal reference range. Bone marrow smear results showed that bone marrow hyperplasia was significantly active, with 50.0% granulocytes and 36.5% erythroid. Ratio of granulocytes and red line cells was 1.37∶1. Proportion of primitive granulocytes and abnormal lymphocytes were 0.5% and 3.5%, respectively. The comprehensive evaluation was complete remission (CR). The patient refused to continue treatment and died 20 months after the onset (February 2018). Conclusion BPDCN is a rare and highly aggressive disease with poor prognosis, and standard treatment protocols for BPDCN has not been established currently. Key words: Dendritic cells; Killer cells, natural; Drug therapy; Prognosis; Blastic plasmacytoid dendritic cell neoplasm

A novel three-way Philadelphia Variant t(9;22;17)(q34;q11.2;q12) in chronic myeloid leukemia: A case report.

Chronic myeloid leukemia (CML) is a hematologic malignancy associated with increased circulating myeloid cells and platelets in the peripheral blood, with accompanying bone marrow hyperplasia. The Philadelphia chromosome, t(9;22)(q34;q11), is present in 95% of CML patients, resulting in constitutive tyrosine kinase activity; however, ~5% of CML patients possess a Philadelphia variant. A novel three-way Philadelphia translocation variant, t(9;22;17)(q34;q11.2;q11.2), was identified in a 54-year old man who presented with leukocytosis, anemia and thrombocytosis that was diagnosed with chronic myeloid leukemia, chronic phase. Cytogenetic analysis by G-banding revealed the presence of a three-way translocation involving the long arms of chromosomes 9, 22 and 17. Fluorescence is situ hybridization utilizing a dual-color fusion probe confirmed the presence of the Bcr-Abl fusion gene.

Impact of bone disease and pain in thalassemia.

Conventional treatment of thalassemia, namely regular blood transfusion and iron chelation, improves perspectives and quality of life; however, successful treatment leads to more time in which long-term complications such as bone disease can develop. Thalassemia bone disease (TBD) is unique: all aspects, from bone anatomy and bone quality to mineral density, may be affected, with important morbidity including osteoporosis, fractures, spinal deformities, nerve compression, and pain. Clinical presentations include growth impairment, rickets-like features, back pain, spinal deformities, any sign of nerve compression, severe osteoporosis, and fragility fractures. Age, history, physical examination, and diagnostic tests support orientation on risk factors. These include bone marrow expansion, toxicity from iron overload and iron chelation, endocrine dysfunctions (hypogonadism, hypohyperparathyroidism, hypothyroidism, growth hormone deficiency, diabetes), and vitamin (D, C, K) and zinc deficiencies. Several of these may coexist in an individual for a long time and at different degrees, making clarification of the relative contribution and selection of the best therapeutic options a challenge. Milestones for prevention of TBD are early and full inhibition of bone marrow hyperplasia and iron toxicity. Empowering patients' positive resources is key for achieving long-term healthy habits with regard to diet, physical activity, sunlight exposure, and lifestyle. Pain, related or unrelated to bone disease, is frequent in thalassemia. The most important targets for the hematologist include having an expert orientation on disease-related causes of pain, driving differential diagnosis, providing effective pain relief and, where feasible, removing the cause.

Utility of 111In-Cl3 scintigraphy for differentiating bone marrow reconversion.

Indium chloride (111In-Cl3) scintigraphy has been used to evaluate various hematological diseases for many years. However, there have been few reports on patients with bone marrow reconversion showing high uptake in 111In-Cl3 scintigraphy. Herein, we report a case of a 68-year-old man with esophageal cancer who underwent 18F-FDG PET/CT for staging of the disease. 18F-FDG PET/CT demonstrated high uptake in the first lumbar vertebral body, which was difficult to distinguish bone metastasis and bone marrow reconversion. 111In-Cl3 scintigraphy demonstrated specific findings with high uptake in the lesion, indicating bone marrow hyperplasia or reconversion.

Efficacy of Shengxue Mixture Combined with Intraosseous Infusion for Treatment of Aplastic Anemia

To evaluate the efficacy and safety of Shengxue mixture combined with intraosseous blood infusion for treatment of aplastic anemia patients. From 2011 to 2015, Institute of blood diseases of Shaanxi Medical University admitted 53 patients with aplastic anemia. The patients were treated with shengxue mixture 200 ml, orally, twice a day. Stanozolol tablets, Adult 2 mg, three times a day, mycophenolate mofetil 1.0 g, twice a day. Intraosseous infusion of the following medicine were administered in patients: recombinant human EPO 10000 U, recombinant human G-CSF 450 µg, recombinant human IL-11 4.5 mg, dexmethasone 20 mg, once a week, a total of four times. One month later, the blood cell counts and bone marrow biopsy were performed. Consolidation treatment continued for 3 to 6 months after discharge, and therapeutic effect was observed and followed-up for more than a year. After one month of treatment, 40 patients were basically cured (75.47%), 8 patients were remitted(15.09%), Hemoglobin level, white blood cell count and platelet count were significantly improved after treatment (P<0.01). The overall response rate was 90.57%(48 patients). Patients with bone marrow hyperplasia was 46 (86.79%), versus 9(16.98%) before treatment. There was a difference (P<0.05). After 3 to 6 months of treatment, 40 patients were cured (75.47%); 8 patients were remitted(15.09%); 3 patients were obviously improved(5.66%); 2 patients were ineffective(3.77%). The overall response rate was 96.23%(51 cases). No obvious side effects were observed. No patients were relapsed after one year. Shengxue mixture combined with Intraosseous infusion is a fast, efficient, safe method for the treatment of aplastic anemia.

Rangeliosis: histopathological analysis, hematology and molecular detection of canine Rangelia vitalii in Rio Grande do Sul, Brazil

ABSTRACT: In the period from January 2004 to December 2015, 56 dogs were diagnosed with rangeliosis in the Setor de Patologia Veterinária at Universidade Federal do Rio Grande do Sul (SPV-UFRGS). The main hematological abnormalities were thrombocytopenia and anemia. The affected dogs showed signs of apathy, anorexia, fetid and bloody diarrhea, vomiting, and dehydration. At necropsy, the main changes were jaundice, splenomegaly, hepatomegaly, and lymphadenomegaly. Histological analyses revealed parasitophorous vacuoles of Rangelia vitalii in cytoplasmic endothelial cells, mainly in the heart, kidneys, lymph nodes, intestines, and pancreas. Inflammation characterized by mononuclear cells was predominant in the analysis, and most was due to the presence of plasma cells. Other lesion types observed were lymphoid hyperplasia, extramedullary hematopoiesis, erythrophagocytosis, and erythroid lineage hyperplasia in bone marrow. Of the total number of animals, 49 were diagnosed using necropsy and histological analysis, and seven were diagnosed using a molecular analysis (i.e., PCR and genetic sequencing of blood samples). This paper presented a different method of diagnosing rangeliosis in canines. This approach involved histological methods including the quantification and determination of the intensity and distribution of the infectious agent in different organs.

Medical follow-up of the exposed victim two years after " 5.7" radiation accident in Nanjing

Objective To investigate the late effects induced by ionizing radiation and the rehabilitation treatment of local radiation injury by medical follow-up of the patient exposed to192Ir at 5.7 accident in Nanjing, and to provide more experience for the treatments in the medical emergency of nuclear or radiological accident. Methods According to the history inquiry and physical examination of the patient in detail and the record of clinical symptoms and signs, the changes of the blood system, immune system, reproductive system, eyes, nervous system were systematically evaluated. The effects of rehabilitation treatment for the patient with lower limb dysfunction were also assessed. Results After the medical treatments of the patient, the hematopoietic immune system was restored, but the bone marrow aspiration still showed low bone marrow hyperplasia in right ilium. Meanwhile, the level of sex hormones was within the normal range, but semen examination showed sperm motility was 0. The radiation damage also occurred in the eye lens, retina and fundus. However, the psychological evaluation showed that the patient was stable and the right lower limb skin wound healing was well except for dysfunction and pain in some extent, which was relieved after the rehabilitation treatment. Conclusions The physiological function of the exposed victim with mild bone marrow type acute radiation sickness could be completely or partially restored after the clinical treatment in the early stage. Key words: Radiation accident; Bone marrow form of acute radiation sickness; 192Ir; Late effects; Medical follow-up

New evidence suggesting a dissociated etiology for cribra orbitalia and porotic hyperostosis.

Porotic hyperostosis (PH), characterized by porotic lesions on the cranial vault, and cribra orbitalia (CO), a localized appearance of porotic lesions on the roof of the orbits, are relatively common osteological conditions. Their etiology has been the focus of several studies, and an association with anemia has long been suggested. Anemia often causes bone marrow hypertrophy or hyperplasia, leading to the expansion in trabecular or cranial diploic bone as a result of increased hematopoiesis. Hypertrophy and/or hyperplasia is often coupled with a disruption of the remodeling process of outer cortical bone, cranially and/or postcranially, leading to the externally visible porotic lesions reported in osteological remains. In this article, we investigate whether individuals with CO have increased thickness of the diploë, the common morphological direct effect of increased hematopoiesis, and thus test the relationship between the two conditions, as well as explore the type of anemia that underlie it. An analysis of medical CT scans of a worldwide sample of 98 complete, young to middle-aged adult dry skulls from the Duckworth Collection was conducted on male and female cribrotic individuals (n = 23) and noncribrotic individuals (n = 75), all of whom lacked any evidence of porotic lesions on the vault. Measurements of total and partial cranial thickness were obtained by virtual landmark placement, using the Amira 5.4 software; all analyses were conducted in IBM SPSS 21. Cribriotic individuals have significantly thinner diploic bone and thicker outer and inner tables than noncribriotic individuals, contrary to the expected diploic expansion that would result from anemic conditions associated to bone marrow hypertrophy or hyperplasia. Additionally, individuals without CO and those with the condition have distinctive cranial thickness at particular locations across the skull and the severity to which CO is expressed also differentiates between those with mild and those with a moderate to severe form of the condition. Our results suggest a complex pattern of causality in relation to the pathologies that may lead to the formation of porotic lesions on the vault and the roof of the orbits. A form of anemia may be behind the osteological changes observed in PH and CO, but it is unlikely to be the same type of anemic condition that underlies both types of osteological lesions. We suggest that CO may be associated to anemias that lead to diploic bone hypocellularity and hypoplasia, such as those caused by anemia of chronic disease and, to a lesser extent, of renal failure, aplastic anemia, protein deficiency, and anemia of endocrine disorders, and not those that lead to bone marrow hypercellularity and hyperplasia and potential PH. This leads us to the conclusion that the terms PH and CO should be used to reflect different underlying conditions.

Significance of Simultaneous Analysis of Bone Marrow Smear and Bone Marrow Biopsy in the Diagnosis of Lymphoma

To explore the value of bone marrow smear combined with biopsy in the diagnosis of lymphoma. Clinical data of 50 cases of lymphoma from our hospital were analyzed retrospectively, and the results of the bone marrow smear and the bone marrow biopsy were compared simultaneously. The decision for the degree of bone marrow hyperplasia in bone marrow biopsy slice was superior to that in smear, and the active or highly active hyperplasia of nucleated cells were observed in all the bone marrow biopsies; the lymphomatic cells were observed in bone marrow smear of the 12 patients(24%), but the bone marrow biopsies showed a higher detection rate of lymphomatic cells 44% in 22 patients(P<0.05); The hyperplasia of bone marrow fibrous tissue, mainly mild to moderate, were the common in cases with bone marrow involvement and the severity of bone marrow fibrosis positively correlated with the number of lymphomatic cells. Biopsy combined with aspiration can improve the accuracy of diagnosis in lymphoma with bone marrow involvement.

Clinicopathologic characteristics of plasma cell myeloma with marrow fibrosis

Objective: To study the clinicopathologic features of plasma cell myeloma(PCM) with bone marrow fibrosis (MF). Methods: The clinicopathologic data of 175 cases of newly diagnosed PCM patients were retrospectively analyzed. Based on reticular fiber staining, these cases were divided into PCM-MF and non-PCM-MF groups. Results: Sixty-three cases were PCM-MF(36%), 112 were non-PCM-MF (64%). No statistical difference in gender, age, hemoglobin level, platelet counts, the classification of immunoglobulin, ISS staging, immunohistochemical phenotypes and genetic features was found between PCM-MF and non-PCM-MF groups (P>0.05). Compared to non-PCM-MF group, lactate dehydrogenase (LDH)level and renal impairmentrate were higher in PCM-MF group (P<0.05). The degree of bone marrow hyperplasia, the percentage of myeloma cells and cells with plasmablastic morphology were significantly higher in PCM-MF group(P<0.05). Conclusion: The higher LDH level, renal impairment rate, and more significant bone marrow hyperplasia, proliferation of plasma cells and plasmablastic myeloma cells infiltration indicate poor prognosis of PCM-MF patients.

Bone marrow hyperplasia detected by gated blood pool imaging

Technetium-99m RBC gated blood pool ventriculography study or multigated acquisition (MUGA) is a commonly employed imaging study to determine the left ventricle ejection fraction and regional wall motion. However, tracer distribution at abnormal sites requires further evaluation. We present the case of a young thalassemia patient with significant tracer uptake in the rib cage as observed in the planar images of MUGA study helping in the demonstration of scintigraphic evidence of bone marrow hyperplasia.

Abstract P4-21-36: Splenic enlargement and bone marrow hyperplasia in patients receiving trastuzumab-emtansine for metastatic breast cancer

Abstract Introduction Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate used for treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. An association between T-DM1 and splenic enlargement was noted anecdotally on sequential whole-body MRI (WB-MRI) examinations. A retrospective analysis of WB-MRI examinations of patients on T-DM1 was undertaken to investigate the hypothesis that an increase in splenic volume is due to either a generalised hyperplasia of the bone marrow and reticulo-endothelial system and/or an increase in portal venous pressure. Methods 12 patients underwent 29 serial WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow muscle-normalised signal intensity (nSI), water diffusivity (apparent diffusion coefficient, ADC) and fat fraction were measured. Changes in splenic volume were analysed, and correlations between the measured variables were obtained. Results An increase in splenic volume was observed in 92% of patients. Mean splenic volume increased from 144cm3 (95%CI 110-177cm3) to 209cm3 (95%CI 161-257cm3) on T-DM1 therapy (p=0.006). Increase in splenic volume correlated with treatment duration (r2=0.71). Increase in normal bone marrow signal was seen (nSI 3.5 to 4.8, p=0.12), along with a decrease in fat fraction (64.3% to 57.3%, p=0.12), and reduced ADC (655µm2/s to 543µm2/s, p=0.11). No consistent changes to portal vein diameter were seen. Discussion An increase in splenic volume was consistently observed in patients on T-DM1 therapy. This was unrelated to portal vein changes but correlated with bone marrow hyperplasia. Caution should be applied when assessing metastatic disease in bone to avoid incorrectly attributing T-DM1-related changes in normal bone marrow to disease progression. Citation Format: Kosmin M, Makris A, Jawad N, Miles D, Padhani AR. Splenic enlargement and bone marrow hyperplasia in patients receiving trastuzumab-emtansine for metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-36.

Causes of peripheral cytopenia in hepatitic cirrhosis and portal hypertensive splenomegaly.

The clinical data of 183 patients with hepatitic cirrhosis and portal hypertensive splenomegaly complicated by peripheral cytopenia were retrospectively analyzed to investigate the causes of peripheral cytopenia, as well as the proportion of the causes in these patients. All patients underwent splenectomy. Before operation, these patients had one or more types of peripheral cytopenia (cumulative cytopenia: 390 patient-times). After splenectomy, blood counts in 79.2% (309/390) returned to normal, while in 15.9% (62/390) they increased but failed to reach to normal levels, and in 4.9% (19/390) they became lower than before the operations. For the last group of patients ( n = 19), long-term follow-up showed that blood counts returned to normal in five patients. In other words, in 80.5% [(309 + 5)/390 or 314/390] of patient-times, the peripheral cytopenia was due to hypersplenism, in 15.9% it was due to a combination of factors, and in 3.6% [14/390] it had nothing to do with the hypersplenism. Thus, hypersplenism is a major cause, but not the only cause, of peripheral cytopenia in patients with hepatic cirrhosis and portal hypertensive splenomegaly, and splenectormy is an effective treatment for these patients. Impact statement For a long time, the development of peripheral cytopenias as a complication to cirrhotic portal hypertension has been attributed to hypersplenism; however, this has never been fully demonstrated. Dameshek summarized that hypersplenism should be diagnosed by the presence of four conditions: (a) mono- or multi-lineage peripheral cytopenias; (b) compensatory hyperplasia of bone marrow; (c) splenomegaly; and (d) correction of cytopenias after splenectomy. We retrospectively analyzed the clinical data from 183 surgical patients, and found that 80.5% of peripheral cytopenias was caused by hypersplenism, 16% by a combination of factors, and 3.5% by other factors unrelated to hypersplenism. As the first quantitative findings in this field, our results verify that hypersplenism is a major, but not exclusive, cause of peripheral cytopenias, and provides important clinical evidence for investigating the cause of peripheral cytopenias.

Splenic Enlargement and Bone Marrow Hyperplasia in Patients Receiving Trastuzumab-Emtansine for Metastatic Breast Cancer.

An association between trastuzumab-emtansine (T-DM1) and splenic enlargement is reported in preclinical data, and has been noted anecdotally in patients receiving T-DM1 at our institution. Use of whole-body MRI examinations (WB-MRI) allows for detailed bone marrow assessment and semi-automated splenic volume calculations. To retrospectively evaluate changes in splenic volume versus evidence of bone marrow hyperplasia and/or changes in portal venous pressure in patients receiving T-DM1 for metastatic breast cancer. Twelve metastatic breast cancer patients underwent 29 WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow diffusion-weighted normalised signal intensity (nSI), quantitative water diffusivity (apparent diffusion coefficient, ADC) and fat fraction (rF%) were measured and correlated. Splenic volume increases were observed in 92% of patients. Mean splenic volume increased from 144cm3 (95% CI 110-177cm3) to 209cm3 (95% CI 161-257cm3) on T-DM1 therapy (p = 0.006). Splenic volume increases correlated with treatment duration (r2 = 0.43). Bone marrow hyperplasia was evidenced by an increase in bone marrow nSI (3.5 to 4.8, p = 0.12), and decreases in rF% (64.3% to 57.3%, p = 0.12) and ADC (655μm2/s to 543μm2/s, p = 0.11). No changes to portal vein diameter were seen. Previously unreported increases in splenic volume and bone marrow hyperplasia are observed on WB-MRI in patients on T-DM1 therapy. Caution must be applied to avoid misinterpreting T-DM1-induced bone marrow hyperplasia as diffuse disease progression in bone.

Clinical analysis in a cohort of 102 patients with myelodysplastic syndrome characterized by erythroid hyperplasia

Objective: To investigate the clinical and laboratorial characteristics of patients with myelodysplastic syndrome (MDS) and erythroid hyperplasia. Methods: MDS patients whose bone marrow was hypercellular with erythroid lineage more than 50% and blasts account for less than 20% of non-erythroid cells were enrolled in this study. The ratio of mature erythrocytes to nucleated erythrocytes was no more than 20, namely MDS patients with erythroid hyperplasia(MDS-E). The retrospective analysis comprised 102 patients with MDS-E from the First Affiliated Hospital of Suzhou University. Clinical characteristics, karyotype, and the prognostic significance of erythroid hyperplasia were evaluated. Results: A total of 48 MDS-E patients (47.1%) presented a variety of cytogenetic abnormalities. The most frequently involved chromosomes were chromosome 8 (39.5% of all abnormal karyotypes), chromosome 7 (22.9%), followed by chromosome 5 (18.8%), chromosome 1 (16.7%) and chromosome 20 (16.7%). Hemoglobin (Hb) level affected the prognosis by survival analysis. The overall survival (OS) of MDS-E patients with Hb equal or more than 70 g/L was longer than that of patients less than 70 g/L (P<0.001). Allogeneic hematopoietic stem cell transplantation (HSCT) significantly improved the OS compared with best supportive care (P<0.001) and chemotherapy (P<0.001). The extent of erythroid hyperplasia in bone marrow did not impact on prognosis (P=0.187). Conclusions: Compared with previous reports of MDS patients, MDS-E patients have higher level of erythroid hyperplasia, more common erythroid dyshematopoiesis, more frequent 8 and 1 chromosome abnormalities. The degree of erythroid hyperplasia is not correlated with prognosis. Allogeneic hematopoietic stem cell transplantation improves the prognosis.