Extramedullary Hematopoiesis In Patient Research Articles

Extramedullary Hematopoiesis in Myelodysplastic Syndromes: A Systematic Literature Review

Extramedullary hematopoiesis is rarely seen in patients with myelodysplastic syndromes, and its clinical characterizations are not well-defined. Here, we systematically reviewed the published literature to summarize the clinical manifestations, treatments, and long-term outcomes of biopsy-proven extramedullary hematopoiesis in patients with myelodysplastic syndromes. We included 41 patients, and ring sideroblasts were the most common myelodysplastic subtype (30.6%). Extramedullary hematopoiesis was typically symptomatic on presentation due to local compression, frequently involving the liver or spleen (36.6%), or the paravertebral region (24.4%). Notably, ring sideroblasts were predominantly seen in patients with non-hepatosplenic involvement (38.5 vs. 6.7%, p = 0.034). Interventions, when required, usually included surgery (36.8%) or radiation (13.2%), which led to symptomatic improvement in 55.5% of patients. The median overall survival of the current cohort was 7 months. The current study confirms the rarity of extramedullary hematopoiesis as a complication of myelodysplastic syndromes; however, its outcomes in response to systemic modern therapies require further investigation.

The Correlation Between Ineffective Erythropoiesis Biomarkers and Development of Extramedullary Hematopoiesis in Patients with Thalassemia.

Introduction: Extramedullary hematopoiesis (EMH) is one of the main complications in patients with thalassemia in compensation for the underlying ineffective erythropoiesis. This study aimed to evaluate the association between ineffective erythropoiesis biomarkers and EMH in patients with thalassemia.
 Methods: A cross-sectional study of thalassemia patients aged >18 years old at Srinagarind Hospital was performed. Phosphatidylserine-exposed red blood cells (PS-exposed RBCs) were studied by flow cytometry. The levels of growth differentiation factor-15 (GDF15) and soluble transferrin receptor (sTfR) levels were determined using ELISA.
 Results: One hundred and thirty-one patients were enrolled. EMH was found in 34 patients (26.0%). EMH was more prevalent among patients with β-thalassemia as compared to those with α-thalassemia (36.4% vs. 4.7%). The levels of GDF15 and sTfR were different between the two groups and indicated a greater degree of ineffective erythropoiesis in β-thalassemia patients. The levels of PS-exposed RBCs showed a modest correlation with EMH. Advanced age and the PS-exposed RBC levels had a statistical significance associated with EMH.
 Conclusions: Advanced age and high PS-exposed RBC levels are associated with EMH in thalassemia. PS-exposed RBCs showed a modest correlation with EMH and may be used to predict the development of EMH in thalassemia.

Comprehensive Review: Extramedullary Hematopoiesis in Patients with Beta Thalassemia Major (transfusion dependent thalassemia)

AbstractIntroduction:Thalassemia is one of the most common hemoglobinopathies, with around 5% of world's population expected to have some degree and type of thalassemia. Beta thalassemia (BT) occurs due to a deficient production of the beta-globin chain of hemoglobin. BT is classified into minor, intermedia, and major, defined by their clinical and laboratory findings. Extramedullary hematopoiesis is one of the complications of BT, primarily seen in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta thalassemia major (BTM). However, there are multiple case reports of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. However, given the increasing cases, it seems that the true incidence is much higher than expected. This systematic review aims to pool the available data and provide cumulative evidence on the occurrence of EMH in BTM patients.Methods:This is a systematic review of case reports, series, and retrospective studies that presented data on the occurrence of EMH in BTM patients. Data were recorded and analyzed in Microsoft Excel 2016 and SPSS 26. The protocol has been registered in PROSPERO: CRD42021242943.Results:Data from 253 cases of EMH in BTM patients were extracted from 2 retrospective studies and 71 case reports (some of the descriptive data from case reports and most of the descriptive data from retrospective studies was missing). The mean age at presentation was 35.3 +/- 0.5 years. Males constituted 57.7% of the total population. Mean hemoglobin at presentation with EMH was 8.2 +/- 2.1 mg/dL. Lower limb weakness was the most common presenting feature (N=23). Other features included localized pain, urinary incontinence, and an incidental finding of EMH. Magnetic resonance imaging (MRI) was the most widely used diagnostic modality (N=226). However, computed tomography scans, positron emission tomography scans, tissue biopsy, myelograms, and X-rays were also used to diagnose EMH. Various treatments were reported either alone or in combination. Overall, blood transfusion was the commonest reported treatment (N=30), followed by radiotherapy (N=20), surgery (N=15), hydroxyurea (N=12), steroids (N=6), and exchange transfusion (N=2). An outcome was reported in 20% of patients, all recovered, with no reported mortality.Conclusion:EMH is considered a rare phenomenon in BTM patients. However, there are many cases reported in which EMH occurred in BTM despite chronic blood transfusions. EMH can occur in any organ system and can present with a varied clinical feature. MRI can effectively diagnose EMH, and conservative management is reported to have similar results compared to invasive treatments. More extensive studies, focusing especially on outcomes, are required to enhance the guidelines on managing EMH in patients with BTM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Poster: MPN-246: General Characteristics and Outcome of Renal Extramedullary Hematopoiesis in Patients with Myeloproliferative Neoplasms: A Literature Review

Poster: MPN-246: General Characteristics and Outcome of Renal Extramedullary Hematopoiesis in Patients with Myeloproliferative Neoplasms: A Literature Review

MPN-246: General Characteristics and Outcome of Renal Extramedullary Hematopoiesis in Patients with Myeloproliferative Neoplasms: A Literature Review

Context: Kidneys are a rare but serious site for extramedullary hematopoiesis (EMH) with myeloproliferative neoplasms (MPNs). Objective: To review cases of EMH affecting the kidneys, focusing on demographics, clinical manifestations, treatment, and outcomes. Design and Setting: We reviewed the literature for studies, case series, and case reports that reported on renal EMH with a primary or background diagnosis of MPN from 1990 to 2020. Results: Forty-three patients (79% males) were retrieved. The mean age of the cohort was 65 years (range 49–87 years). Most of the cohort was white Caucasian (91%). The type of MPN was mostly MF, seen in 35 patients (81.4%), while PV was seen in 5 patients (11.6%), and ET and CML were seen in 2 patients (4.7%) and 1 (2.3%) patient, respectively. The most common renal manifestations were renal failure and nephrotic syndrome in 39.5% of the cases, followed by renal failure alone (37.2%) and nephrotic syndrome in 9.3%. Interestingly, a renal mass was found in 9%. The average time to EMH development from the time of diagnosis was 7.8 years (range 0–20 years). Four patients developed EMH post-transplant, 3 of them allogenic while one was autologous. The JAK mutation was reported in 7 patients, and CALR mutation in one patient. Patients were treated with different medications, including diuretics, anti-hypertensives (mainly ACE inhibitors), and steroids. However, for MPNs, 25% received HU, 14% received thalidomide or a thalidomide analog, while 16% received JAK inhibitors, such as ruxolitinib. The CML case was treated with imatinib. The average duration of follow-up was 19 months, with a 42.5% death rate by the end of follow-up. Kidney function improved in 31% of patients, with ruxolitinib administration correlating with improved kidney function and survival (6 out of 7 patients). Conclusions: An unexplained increase in renal function, proteinuria, or kidney mass in a setting of MPN should raise the suspicion of this diagnosis. There is currently no consensus or guidelines on the management of such cases. Ruxolitinib, with the limitations of small numbers treated, may offer some benefit; however, further studies and exploration of this drug and others in well-constructed prospective studies are needed.

Preliminary Data Show Heterogenous Patterns of 18f-FDG PET/CT When Assessing the Inflammatory Component of Primary or Secondary Myelofibrosis

Abstract Background. Recent studies have highlighted the interest of non-invasive procedures to assess extramedullary hematopoiesis in patients with overt myelofibrosis, primary (PMF) or secondary (sMF) to essential thrombocytemia (ET) or to polycythemia vera (PV) (1-4). Several nuclear medicine imaging techniques have been employed without clear consensus about the predominant value of one over other in these mostly preliminary works (2-4). Population and objectives. Because the pathophysiology of PMF or sMF involves some inflammatory pathways we studied the interest of 18F-FDG (18F-fluorodeoxyglucose) PET/CT in patients with PMF (5). The main objective was to know whether the inflammatory component of PMF could be well detected by this technique. Secondly, we looked for some kind of correlation between the FDG uptake on medullary and extramedullary sites of hematopoiesis and the severity of the disease. Five patients with diagnosis of MF (3 PMF and 2 sMF) were assessed (see Table 1 for baseline characteristics and results) Methods.18F-FDG PET/CT imaging was performed following a 60 min. uptake after intravenous injection of a weight-adapted FDG activity (2,5 MBq/kg) on a Siemens Biograph mCT. Images were reviewed by board certified nuclear medicine physicians. Spleen size was measured on axial slices. SUVmax were assessed in a 5 mm diameter spheric volume of interest in homogenous parts of liver and spleen, and in the L2 vertebral body for axial skeleton assessment. Spleen uptake was considered as abnormal in case of a diffuse uptake exceeding hepatic baseline uptake. Skeleton uptake was considered as abnormal in case of diffuse increased uptake. Results. UPN01LP: slight higher metabolic activity in the axial skeleton and diffuse spleen uptake ; UPN02AP: no hypermetabolic activity in the spleen and slightly higher uptake in the axial skeleton ; UPN03AA: diffuse bone hypermetabolic activity and high metabolic activity in the spleen ; UPN05HL: diffuse bone hypermetabolic activity and higher metabolic activity in the spleen ; UPN06DF: no diffuse hypermetabolic activity in the spleen, slight higher uptake in the axial skeleton. In summary, those patients with overt myelofibrosis and constitutional signs tend to show a diffuse higher activity both in the axial skeleton and the spleen whereas those without overt myelofibrosis and without constitutional signs tend to present a normal metabolic activity in the axial skeleton and in the spleen. These patterns are in accordance with the progression and severity of the disease. The higher uptake of 18FDG in the axial skeleton in patients with overt MF contrasts with what is observed with some hybrid imaging techniques that show a lower radionuclide (111In/SPECT/CT) uptake at this level translating a lower hematopoietic activity (3). Conclusions. Based on these preliminary results we consider 18FDG-PET/CT procedures are able to detect the inflammatory component of PMF or sMF and the intensity of FDG uptake appears to be correlated to the severity of the disease. Those patients with a high metabolic activity in the axial skeleton and the spleen might be candidates for specific therapies, although these statements need to be confirmed in a larger series of patients. Bibliography. 1 Derlin T et al. Assessment of bone marrow inflammation in patients with myelofibrosis: an 18F-fluorodeoxyglucose PET/CT study. Eur J. of Nucl Med Mol Imaging 2015 2 Agool A et al. Radionuclide imaging of bone marrow disorders. Eur J Nucl Med Mol Imaging. 2011. 3 Ojeda-Uribe M et al. Assessment of sites of marrow and extramedullary hematopoiesis by hybrid imaging in primary myelofibrosis patients. Cancer Medicine 2016. 4 Vercellino L et al. Assessing bone marrow activity in patients with myelofibrosis: results of a pilot study of 18F-FLT PET. J. of Nucl Med 2017. 5 Desterke C et al. Inflammation as a Keystone of Bone Marrow Stroma Alterations in Primary Myelofibrosis. Mediators Inflamm. 2015 Download : Download high-res image (107KB) Download : Download full-size image Table 1 . Disclosures No relevant conflicts of interest to declare.

Progressive compressive thoracic myelopathy

Extramedullary hematopoiesis is a possible complication in patients with beta-thalassemia, due to ineffective erythropoiesis, producing remote sites of hematopoiesis in multiple and very variable anatomic locations [1Gatto I. Terrana V. Biondi L. Compression of the spinal cord due to proliferation of bone marrow in epidural space in a splenectomized person with Cooley's disease.Haematologica. 1954; 38: 61-76PubMed Google Scholar, 2Haidar R. Mhaidli H. Taher A.T. Paraspinal extramedullary hematopoiesis in patients with thalassemia intermedia.Eur Spine J. 2010; 19: 871-878Crossref PubMed Scopus (126) Google Scholar]. Among these sites, spinal epidural extramedullary hematopoiesis carries potential risk and may lead to acute irreversible neurological deficits [[3]Salehi S.A. Koski T. Ondra S.L. Spinal cord compression in beta-thalassemia: case report and review of the literature.Spinal Cord. 2004; 42: 117-123Crossref PubMed Scopus (47) Google Scholar]. Surgery has been used as a treatment option, however there have been reports of significant blood loss [3Salehi S.A. Koski T. Ondra S.L. Spinal cord compression in beta-thalassemia: case report and review of the literature.Spinal Cord. 2004; 42: 117-123Crossref PubMed Scopus (47) Google Scholar, 4Lau S.K. Chan C.K. Chow Y.Y. Cord compression due to extramedullary hemopoiesis in a patient with thalassemia.Spine. 1994; 19: 2467-2470Crossref PubMed Scopus (35) Google Scholar, 5Garg K. Singh P.K. Singh M. et al.Long segment spinal epidural extramedullary hematopoiesis.Surg Neurol Int. 2013; 4: 161Crossref PubMed Google Scholar]. In our case, after multidisciplinary discussion, emergency surgical decompression was chosen due to the rapidly progressive paraparesis during the preceding48 hours since admission. It was felt that this would provide speedier decompression over radiotherapy. Additionally, appropriate preoperative hematologic optimization (tranexamic acid, blood and platelet transfusions) was also instigated. After induction of general anesthesia, left T5-T9 hemilaminectomies) were performed (Fig. 2). Total intraoperative blood loss was estimated at 200cc. No supplementary hematologic treatment was needed in the postoperative period. We underline the need for surgical management in cases of progressive spinal cord compression [2Haidar R. Mhaidli H. Taher A.T. Paraspinal extramedullary hematopoiesis in patients with thalassemia intermedia.Eur Spine J. 2010; 19: 871-878Crossref PubMed Scopus (126) Google Scholar, 4Lau S.K. Chan C.K. Chow Y.Y. Cord compression due to extramedullary hemopoiesis in a patient with thalassemia.Spine. 1994; 19: 2467-2470Crossref PubMed Scopus (35) Google Scholar]. It can be performed safely and without excessive hemorrhagic risk. In our case we used a unilateral approach which allowed complete decompression. This approach also limits blood loss and preserves soft tissue and bony structures on the contralateral side. Adequate preoperative hematologic status is essential in these cases. Radiation therapy was used as an adjuvant treatment postoperatively to prevent recurrence of epidural extramedullary hematopoiesis. Follow-up was performed at 6 weeks and 3 months. Complete neurologic recovery was observed, with no recurrence at 3 months MRI (Fig. 3). In conclusion, the optimal management for extramedullary hematopoiesis with neurological impairment remains unproven and is currently based on case-by-case situations. We suggest that surgical management can be safely performed with optimal hematologic preparation without incurring excessive intraoperative blood loss. Note 1: A signed patient consent form has been supplied for publication. Note 2: Posthumous authorship for Dr Christian Wider.

Extramedullary Hematopoiesis in Patients with Primary Myelofibrosis Rare and Serious Complications

Extra Medullary Hematopoiesis refers to the presence of hemopoietic elements in locations other than the bone marrow medullary space,It may be seen in many conditions, including chronic hemolytic anemias like thalassemia Intermedia or major. The common sites of involvement are the liver, spleen and the lymph nodes. Less common sites include the central nervous system, adrenal gland, kidney, perirenal soft tissues, breast, peritoneum and gastrointestinal tract the paraspinal region is a relatively uncommon location for these hemopoietic deposits. There are a few case reports of EMH occurring in the spineMost cases have been reported in connection with thalassemia, although it has also been described in patients with sickle cell anemia, polycythemia vera ,myelodysplastic syndrome and myelofibrosis. To the best of our knowledge, there are very few documented case reports in the literature of patients with myelofibrosis who developed cord compressive symptoms due to EMH in the spine from 1958 till 2016 only 15 cases were reported, In reported cases male to female ratio 7:1 with age range between 30 and 75 year old Paraprasesis are the most common presenting symptoms Thoracic region is the most affected site The degree of anemia and bone marrow fibrosis does not correlate with the occurrence of EMH since it was reported in cases with early fibrosis or mild anemia. Correlation between molecular markers like JAK2 and CALR, MPL is not describedNo definite guidelines have as yet been formulated for the treatment of such patients with EMH. Excision and decompression, radiotherapy, hypertransfusion and hydroxyurea alone or in combination have been proposed as well as lack of consensus about what is complete remission is it clinical or clinical and radiological and what is partial response is it any reduction of the mass lesion or any degree of clinical improvement in conclusion there is necessity to establish consensus for treatment and definition of CR, PR or No response in EMH with MF. DisclosuresNo relevant conflicts of interest to declare.

The effects of hematopoietic stem cell transplant on splenic extramedullary hematopoiesis in patients with myeloproliferative neoplasm-associated myelofibrosis

Background/objectiveHematopoietic stem cell transplant (HSCT) is the only curative treatment for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF). The main clinical manifestation of MPN-MF is splenomegaly secondary to extramedullary hematopoiesis (EMH). The effects of HSCT on splenic EMH and associated vascular and stromal changes are unknown. This study compares the findings seen in spleens following HSCT with those of nontransplanted patients, normal controls, and matched bone marrow (BM) samples. MethodsThis study included three transplanted MPN-MF spleens, three nontransplanted MPN-MF spleens, and three normal controls. Spleens were assessed for: (a) presence/extent of EMH; (b) presence of Gamna–Gandy bodies; (c) splenic fibrosis; (d) CD34-positive microvessel density; (e) CD8-positive sinusoids; (f) frequency of smooth muscle actin-positive myoid cells; and (g) nerve growth factor receptor-positive adventitial reticulum cells. In two cases, matched BM samples were assessed for cellularity, presence of atypical megakaryocytes, and fibrosis. ResultsCompared with normal controls, all MPN-MF spleens were larger in size, had EMH, red pulp fibrosis, higher CD34-positive microvessel density, and decreased CD8-positive sinusoids. Compared with nontransplanted cases, post-HSCT spleens showed disappearance or reduction of EMH. Gamna–Gandy bodies were increased; no differences in the remaining parameters were found. A reduction of splenic EMH was associated with normalization of BM cellularity and megakaryopoiesis. ConclusionHSCT reduces/abrogates splenic EMH and is associated with an increased number of Gamna–Gandy bodies, which may suggest vascular damage. The lack of stromal changes in spleens removed shortly after transplant is in line with similar observations in the BM, where a longer interval is often necessary for resolution of fibrosis.

Spinal Cord Compression Due to Extramedullary Hematopoiesis in a 27-Year-Old Man with Beta Thalassemia Intermedia: A Case Report

Extramedullary hematopoiesis (EMH) occurs commonly in patients with severe thalassemia who receive inadequate treatment. The diagnosis of thalassemia intermedia is purely clinical and is usually made after a period of observation to determine that the patient is able to maintain a satisfactory hemoglobin (Hb) level for a long time without the need for blood transfusions. The incidence of EMH in patients with thalassemia intermedia may reach up to 20%, compared to polytransfused thalassemia major patients where the incidence remains <1% [1]. Besides the usual regions of hematopoiesis, blood cells can be formed in unusual sites like the liver, spleen and lymph nodes to meet the demands of hematopoiesis [2]. There are a few reports where EMH has involved some rare places such as the perirenal and paravertebral regions, paranasal sinuses, clivus, meninges, spinal epidural spaces, prostate, adrenals, pleura, breast, thymus, kidney, sweat gland, broad ligament and retroperitoneal space [2]. This unusual phenomenon, especially when it involves the spinal cord can lead to neurological deficits [3]. A paraspinal location for the hematopoietic tissue occurs in 11-15% of cases with EMH [1]. Abstract

Intrathoracic extramedullary hematopoiesis presenting as tumor-simulating lesions of the mediastinum in α-thalassemia: A case report.

Extramedullary hematopoiesis (EMH) is a rare disease, where hematological disorder drives extramedullary hematopoietic tumor formation in multiple regions of the body. The present study reports a case of EMH presenting as multiple tumor-like lesions of mediastinum in a 61-year-old male with α-thalassemia, which was subjected to a video-assisted thoracoscopic surgery tissue biopsy to differentiate it from other mediastinal tumors. To date, only three cases of EMH in patients with α-thalassemia have been described in the literature. Patients with EMH typically exhibit no hematological disorder preoperatively and therefore EMH is frequently misdiagnosed. In the present study, along with a literature review of the clinicopathological features of EMH, the diagnosis and treatment of this rare case was discussed, in order to differentiate diagnosis, and particularly to distinguish EHM from extramedullary myeloid sarcoma.

Extramedullary hematopoiesis (EMH) in laboratory animals: offering an insight into stem cell research.

Extramedullary hematopoiesis (EMH) is a pathological process secondary to underlying bone marrow (BM) insufficiency in adults. It is characterized by the emergence of multipotent hematopoietic progenitors scattered around the affected tissue, most likely in the spleen, liver, and lymph node, etc. EMH in patients frequently receives less medical attention and is neglected unless a compressive or obstructive hematopoietic mass appears to endanger the patient's life. However, on a biological basis, EMH reflects the alteration of relationships among hematopoietic stem and progenitor cells (HSPCs) and their original and new microenvironments. The ability of hematopoietic stem cells (HSCs) to mobilize from the bone marrow and to accommodate and function in extramedullary tissues is rather complicated and far from our current understanding. Fortunately, many reports from the studies of drugs and genetics using animals have incidentally found EMH to be involved. Thereby, the molecular basis of EMH could further be elucidated from those animals after cross-comparison. A deeper understanding of the extramedullary hematopoietic niche could help expand stem cells in vitro and establish a better treatment in patients for stem cell transplantation.

Final Results of a Phase 1 Study of 18F-FLT Positron Emission Tomography (PET)/Computed Tomography Imaging in Myelofibrosis (FLT-MF-2009 Study)

Background: PET with fluorodeoxyglucose combined with computed tomography is a major tool for the diagnosis, staging and monitoring of treatment response in clinical oncology. 3′-18Fluoro-3′-deoxy-L-thymidine (18F-FLT) is a nucleoside analog that quickly accumulates in proliferating cells, evaluated in clinical studies in various cancers as a PET radiotracer offering non invasive assessment of cell proliferation in vivo. Preliminary results of a pilot study suggested that this technique could be useful to assess bone marrow (BM) activity and extramedullary hematopoiesis in patients with myelofibrosis (MF). We present the final analysis of the FLT-MF-2009 study (EudraCT Number: 2009-016804-21) confirming that FLT PET could be a new technique useful for MF management.Methods: Main inclusion criteria were: a diagnosis of MF according to WHO criteria; BM biopsy available for centralized review; written informed consent. 18F-FLT PET was performed 1 hour after injection of 18F-FLT (provided by AAA), and consisted in a whole-body acquisition. Two nuclear physicians interpreted images in a blinded fashion independently, qualitatively and according to a visual scale, and patients were classified according to 3 distinct patterns. 18F-FLT uptake was quantified using maximum standardized uptake value (SUVmax) in several sites of the skeleton (axial skeleton, proximal and distal territories of upper and lower limbs), in the spleen and the liver. Analysis of factors affecting the intensity of 18F-FLT uptake in these sites (using PET pattern and SUVmax as the endpoints) was performed by using non-parametric tests.Results: 15 patients (mean age: 62 years) were included between Apr 2011 and Jul 2012. 8 patients had primary (PMF), 3 post-polycythemia vera (PV), and 4 post-essential thrombocythemia (ET) MF. 13 patients had a palpable splenomegaly. 10 patients had the JAK2V617F mutation with a median mutant allele burden of 59% (interquartile range: 29-80%), 1 had a MPL515 mutation. Therapies at time of PET included hydroxyurea (n=1), androgens (n=1), interferon (n=4) and ruxolitinib (n=5); 4 patients had no specific therapy for MF.Three patterns of 18F-FLT PET images were observed. Pattern A (n=3) showed a normal BM activity in the central skeleton, a mild expansion to distal extremities and normal splenic uptake. Pattern B (n= 9) displayed a rather normal pattern of BM activity in the central skeleton associated with marked expansion of BM activity to distal extremities and intense uptake of the tracer in the spleen. Pattern C (n=3) showed a marked reduced hematopoietic activity in the central skeleton but a high uptake in spleen, suggesting the existence of myeloid metaplasia.Quantitative analyses of 18F-FLT uptake using SUVmax permitted the search for correlations with clinical and biological characteristics. Grade 3 fibrosis in BM biopsy was significantly associated with low SUVmax values measured in axial skeleton (p=0.019), proximal upper limbs (p=0.016) and proximal lower limbs (p=0.019). Significantly higher SUVmax values in proximal upper (p=0.014) and lower limbs (p=0.021) were associated with the diagnosis of post-PV- vs. post-ET- or PMF. SUVmax values in proximal upper limbs also correlated with the hemoglobin level (Spearman correlation coefficient: 0.53; p=0.038). No significant correlation was found between SUVmax values in any territory and platelet values, JAK2V617F positivity or allele burden, disease duration. Significantly lower SUVmax values were measured in proximal upper limbs of patients treated with ruxolitinib (3.9 ± 2) compared to patients treated with interferon (11.2 ± 5) or untreated patients (7.7 ± 3.1) (p=0.043).Conclusion: The results of this pilot study suggests that 18F-FLT PET could be a new, objective, non invasive technique useful for the evaluation of malignant hematopoiesis in MF, in terms of diagnosis, staging and for monitoring response to therapy. SUVmax values may discriminate post-PV MF from other forms of MF, and may distinguish patients with grade 3 fibrosis. If this latter finding is confirmed in a larger study, 18F-FLT PET could become a convenient substitute to sequential biopsies for the staging of BM fibrosis during the course of the disease. In addition, distinct SUVmax values were found in patients treated with ruxolitinib, suggesting that 18F-FLT PET could also be useful to monitor the efficacy of therapies in MF. DisclosuresOff Label Use: 18F-FLT is an investigational isotope not approved for the imaging of myelofibrosis. Patients treated off-label with interferon were included in the study..

Intracranial extramedullary hematopoiesis in patients with thalassemia: a case report and review of the literature

Extramedullary hematopoiesis (EH) is a compensatory phenomenon that results in the production of blood cell precursors outside the marrow in patients with chronic hemolytic anemia and ineffective erythropoiesis. EH usually involves the liver, spleen, and lymph nodes. It can also be found at paravertebral, intrathoracic, or pelvic locations. Intracranial EH is a rare entity and often asymptomatic but can sometimes lead to symptomatic tumor-like masses. Treatment options are controversial and include hypertransfusion, surgical excision, radiotherapy, and hydroxyurea (HU). Successful treatment of an intracranial EH mass with HU and blood transfusions in a beta-thalassemia major patient was discussed along with a review of the published literature on intracranial EH in thalassemia. In our patient, the extramedullary hematopoietic mass in the interhemispheric fissure showed a marked improvement after 6 months of HU and hypertransfusion therapy. In the English literature, there are a few cases with intracranial EH and thalassemia, which were treated with different treatment modalities, with different outcomes. There is no standard treatment approach in patients with symptomatic EH. HU with hypertransfusion regimen is a reasonable first-choice modality in treating intracranial EH masses.

Abstract No. 304: TIPS for Treatment of Portal Hypertension Due to Extramedullary Hematopoiesis in Patients with Myelofibrosis Secondary to Myeloproliferative Diseases

Abstract No. 304: TIPS for Treatment of Portal Hypertension Due to Extramedullary Hematopoiesis in Patients with Myelofibrosis Secondary to Myeloproliferative Diseases

Janus kinase 2 V617F mutation is detectable in spleen of patients with chronic myeloproliferative diseases suggesting a malignant nature of splenic extramedullary hematopoiesis

Extramedullary hematopoiesis occurs in patients with a variety of hematologic diseases, and the spleen is a common site. Extramedullary hematopoiesis is very common in chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The pathogenesis of extramedullary hematopoiesis is unknown. Using JAK2 V617F mutation as a molecular marker, we assessed paired spleen and bone marrow samples of 15 patients with various types of chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The diagnosis was chronic idiopathic myelofibrosis (n=8), polycythemia vera (n=3), and chronic myelomonocytic leukemia (n=4). DNA was extracted from fixed, paraffin-embedded tissue and assessed for JAK2 V617F by real-time polymerase chain reaction assay followed by melting curve analysis. Concordant JAK2 mutation was detected in the paired samples in 7 patients. A discordant result with JAK2 V617F found in the spleen but not bone marrow was noted in 1 patient. These results indicate that extramedullary hematopoiesis in patients with chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases is a clonal process and lend support to the theory that the cells of extramedullary hematopoiesis are carried from the bone marrow.