Results Of Bone Marrow Examination Research Articles

TP53 Mutational Status in Myelodysplastic Neoplasm and Acute Myeloid Leukemia: Impact of Reclassification By Who 2022 and ICC Criteria - a Korean Multi-Center Study

Introduction: The WHO 2022 classification (WHO 2022) introduced the category of myelodysplastic neoplasm (MDS) with biallelic TP53 inactivation (MDS-bi TP53), while the international consensus classification (ICC) included the categories of MDS, MDS/acute myeloid leukemia (AML), and AML with mutated TP53. Particularly in MDS, multi-hit TP53 mutations are clinically important, but there were differences in the criteria defining multi-hit TP53 mutations between the WHO 2022 and ICC classifications. In this study, we investigated the TP53 mutational status in Korean adult patients with MDS and AML and evaluated the impact of TP53 mutation-related criteria of WHO 2022 and ICC on the reclassification of MDS. Methods: This study included patients aged 18 years or older who were diagnosed with MDS and AML from January 2017 to December 2022 at six institutions. The results of bone marrow examination, chromosome analysis, TP53 fluorescence in situ hybridization, and targeted next-generation sequencing including TP53 were analyzed in 1264 patients with MDS and 2112 patients with AML. Multi-hit TP53 mutation was defined based on WHO 2022 and ICC criteria as having any of the following: one TP53 mutation with variant allele frequency (VAF) ≥ 50%, one TP53 mutation with VAF ≥ 10% with 17p deletion, one TP53 mutation with VAF ≥ 10% with complex karyotype (only for ICC), two TP53 mutations with VAF ≥ 10% (only for ICC), or two TP53 mutations (only for WHO 2022). Results: TP53 mutations were observed in 9.3% (118/1264) and 9.1% (192/2112) of patients with MDS and AML, respectively. Among these, 90% of patients had a single TP53 mutation and multiple TP53 mutations were observed in 10% of patients. There was no difference according to MDS or AML ( P=0.478), and 91% of patients with a single TP53 mutation had a VAF of ≥ 10%. Median VAFs of TP53 mutations were 42.7% and 44.4% in MDS and AML, respectively ( P=0.899), and complex karyotype was observed in 76.1% (236/310) of all patients with TP53 mutations without differences between MDS and AML ( P=0.534). In contrast, 17p deletion was identified in 40.3% of AML patients, significantly higher than in MDS (27.4%, P=0.02). Within MDS, 17p deletion was observed in 46.7% in MDS with 10-19% blasts (MDS-H), significantly higher than in MDS with 0-9% blasts (MDS-L, 20.7%, P=0.008), but similar to AML ( P=0.514). When each TP53 mutation-related criterion based on WHO 2022 and ICC criteria were applied to MDS, 55.7% (49/88) and 75% (66/88) of MDS-L met the criteria for multi-hit TP53 mutation and were classified as MDS-bi TP53 (WHO 2022) and MDS with mutated TP53 (ICC), respectively. Notably, more patients were classified into this category based on ICC criteria ( P<0.001), all due to the complex karyotype-related criterion included only in the ICC. Among MDS-H, 63.3% (19/30) of patients were classified as MDS-bi TP53 (WHO 2022) based on multi-hit TP53 mutation criteria, whereas 86.7% (26/30) of patients were classified as MDS/AML with mutated TP53 (ICC) based on the single TP53 mutation criterion with VAF ≥ 10%. Overall, 57.6% (68/118) and 78% (92/118) of patients with MDS and TP53 mutations were reclassified into the TP53 mutation-related MDS or MDS/AML subgroup according to WHO 2022 and ICC, respectively. Conclusions: TP53 mutation status was not different between MDS and AML, but 17p deletion was observed at approximately 40% in MDS-H and AML, much higher than in MDS-L. Multi-hit TP53 mutation based on WHO 2022 and ICC was present at a relatively high frequency at 60-80% in MDS and AML with TP53 mutations. In particular, when ICC criteria were applied to MDS, 20% more patients were reclassified into TP53 mutation-related MDS or MDS/AML subgroup than when WHO 2022 criteria were applied.

Leukemia can be Effectively Early Predicted in Routine Physical Examination with the Assistance of Machine Learning Models.

The diagnosis of leukemia relies very much on the results of bone marrow examinations, which is never generally performed in routine physical examination. In many rural areas even community hospitals and primary care clinics, the lack of hematological specialist and facility does not allow a definite diagnosis of leukemia. Thus, there will be a significant benefit if machine learning (ML) models could help early predict leukemia using preliminary blood test data in a routine physical examination in community hospitals to save time before a definite diagnosis. We collected the routine physical examination data of 1230 newly diagnosed leukemia patients and 1300 healthy people. We trained and tested 3 machine learning (ML) models including linear support vector machine (LSVM), random forest (RF), and XGboost models. We not only examined the accordance between model results and statistical analysis of the input data but also examined the consistency of model accuracy scores and relative importance order of model factors with regard to different input data sets and different model arguments to check the applicability of both the models and the input data. Generally, the RF and XGboost models give more identical, consistent, and robust relative importance order of factors that is also accordant with the statistical analysis, while the LSVM gives much different and nonsense orders for different inputs. Results of the RF and XGboost models show that (1) generally, the models achieve accuracy scores above 0.9, indicating effective identification of leukemia, and (2) the top three factors that contribute most to the identification of leukemia include red blood cell (RBC), hematocrit (HCT), and white blood cell (WBC), while the other factors contribute relatively less. This study shows a feasible case example for early identification of leukemia using routine physical examination data with the assistance of ML models, which can be conveniently, cheaply, and widely applied in community hospitals or primary care clinics to save time before definite diagnosis; however, more studies are still needed to validate the applicability of more ML models to a larger variety of input data sets.

DIAGNOSTIC ACCURACY OF SERUM FERRITIN AND SOLUBLE SERUM TRANSFERRIN RECEPTOR, TAKING BONE MARROW IRON STAIN AS A GOLD STANDARD FOR IRON DEFICIENCY ANEMIA IN HETEROGENOUS GROUP OF PATIENTS

Objective: To determine the diagnostic accuracy of serum ferritin and soluble serum transferrin receptor (sTfR), taking bone marrow iron stain as a gold standard for iron deficiency anaemia in heterogeneous group of patients.
 Study Design: Cross-sectional diagnostic accuracy study.
 Place and Duration of Study: Department of Diagnostic, Combined Military Hospital Lahore, from Mar to Aug 2020.
 Methodology: A total of 55 adult patients, of both genders, undergoing bone marrow examination for any reason were enrolled. Patients with known hemolytic condition (sickle cell anemia, megaloblastic anemia), taking erythropoietin/iron supplements, transfused red cell concentrate (RCC) recently or undergoing chemotherapy were excluded. Age, gender, clinical history and results of bone marrow examination, complete blood count (CBC), serum Ferritin and C-reactive protein (CRP) were recorded.
 Results: Serum ferritin was found to be less sensitive (28%) but more specific (100%) for reflecting reduced bone marrow iron stores as compared to sTfR (sensitivity: 60%, specificity: 96.6%). sTfR had highest likelihood ratio (15) and diagnostic accuracy (80%). On Receiver Operator Characteristic (ROC) graph Transferrin index (AUC=0.908) showed maximum accuracy, followed by Ferritin (AUC=0.884) and sTfR (AUC=0.879).
 Conclusion: Serum soluble transferring receptor (sTfR) and transferrin index has advantage over serum ferritin alone in predicting the bone marrow iron stores and differentiating iron deficiency anemia from anemia of chronic disease.

Genetic Mutation in Cytopenic Patients: Distinctive Genomic Profile between Preclinical Vs. Clinical Myelodysplastic Syndrome

Genetic mutation in cytopenic patients: Distinctive genomic profile between preclinical vs. clinical myelodysplastic syndrome. Introduction Myelodysplastic syndromes (MDS) are heterogeneous groups of clonal hematopoietic disorders. The current diagnosis of MDS is based on morphologic assessments of dysplasia which are subjected to inter-observer variability and cytogenetic abnormalities which are frequently absent. Somatic mutations in myeloid-related genes have been identified in MDS. However, they are also found in idiopathic cytopenia of unknown significance (ICUS) that shows no significant dysplasia. Therefore, we aimed to explore the clinical implications of genetic mutations in ICUS and compared with MDS. The secondary objective was to find association between degree of dysplasia and somatic mutations. Materials and Methods The patients with peripheral cytopenia ≥1 lineage (ANC < 1,800/mm3, hemoglobin < 10 gm/dL, platelet < 100x109/mL) without explainable causes were enrolled. Bone marrow aspirates were evaluated independently by 2 hematologists. Of note, dysplasia are defined by WHO 2008 classification (eg. Erythroid lineage: ring sideroblasts, megaloblastoid change; granulocytic lineage: hypogranularity, pseudopelger-huet anomaly; megakaryocytic lineage: hypolobate, micro-megakaryocyte). The significant dysplasia cut off was 10% in single lineage or more. If there was a discrepancy, the third hematologist would help to reach the final consensus. We extracted DNA from bone marrow and performed next generation sequencing (NGS) that targeted 143 myeloid-related genes. Results Forty-eight patients were enrolled in this study. The median age at diagnosis was 70 years (71-96). Results of bone marrow examinations were categorized by morphology into 3 groups; non-significant dysplasia (dysplasia < 10%) 27%, low risk MDS (IPSS-R ≤3.5) 42% and high-risk MDS/sAML (IPSS-R >3.5/Blast≥20% in BM or peripheral blood) 31%. Most of cases (77%) carried normal cytogenetics while other genetic alterations were complex chromosome (6%), -Y (6%), del(5q) (4%), trisomy 8 (2%), del(20q) (2%), i(17q) (2%). Thirty from 48 cases (62%) harbored more than 1 somatic mutation. Twenty-eight gene mutations were identified. Mutations were detected 1.6 mutation per 1 patient in average. Most frequent somatic mutations were ASXL1:10/80 (12%), TET2:9/80 (11%), MFDS11: 6/80 (7%), TP53:6/80 (7%), and RUNX1:5/80 (6.25%). The proportions of cases with somatic mutations were not different across the groups (no dysplasia 50%, non-significant dysplasia 80% and significant dysplasia 62%). According to mutation types in each group, mutations in epigenetic pathways were the most frequent mutations across all patient subgroups (ICUS 64.7%, low-risk MDS 51.8 %, and high-risk MDS 52.5%). Mutations in transcription factor were predominated in MDS (18.5% and 25.0% in low-risk and high-risk MDS, respectively) compared to ICUS (11.7%). Individual average frequency of gene mutations was significantly different between disease subtype (high risk MDS 2.7 gene/person, low risk MDS 1.1 gene/person, ICUS 1.3 gene/person (P=.038). Higher variant allele frequency (VAF) of mutated genes was significantly observed in high risk MDS (38.3%) compared to low risk MDS (30.8%) and preclinical MDS (29.0%) (P=.03). Conclusion In conclusion, molecular profiling was significantly different between preclinical MDS and MDS groups in terms of types of somatic mutations and VAF. This unique contrast could be used to distinguish between preclinical MDS and clinically significant MDS. In contrast, degree of marrow dysplasia was not associated with number of gene mutations in this study. Prediction for clinical consequent of somatic mutations in CCUS requires long term follow up. Disclosures No relevant conflicts of interest to declare.

PB1906 FROM ACADEMY TO REAL WORLD: THE GRAY AREA OF THE LARGE GRANULAR LYMPHOCYTES LEUKEMIA

Background:Large granular lymphocytes (LGLs) are defined as large white blood cells (WBC) that are morphologically characterized by an abundant cytoplasm with azurophilic granulation. LGLs belong to CD3+CD56− cytotoxic T cells (CT) or natural killer (NK) cells. The NK cells are roughly defined by a lack of the T cell marker CD3 and a presence of CD56 (or NCAM). LGL leukaemia represents a chronic lymphoproliferative disorder of CTLs, a malignancy that involves lymphocyte infiltration of multiple organs, including the BM, liver, and spleen.Aims:The aim of this retrospective study was to achieve information about LGL and the association between LGL and clinical characteristics.Methods:A retrospective study analyzing the global diagnosis of LGL leukaemia and factors influencing the disease evolution at the district hospital and included cases with the previous or recent diagnosis of LGL leukaemia between January 2015 and December 2018. Special emphasis was taken on the results of bone marrow examination, flow cytometry, immunophenotype, and results of molecular studies to assess for T‐cell receptor (TCR) gene rearrangements. A total of 26 patients were confirmed as having LGL leukaemia, and they fulfilled the WHO classification criteria. May‐Grünwald‐Giemsa–stained peripheral blood smears were examined for the presence of large granular lymphocytes. Bone marrow trephine biopsy and aspirate specimens (when was applicable) were obtained. Bone marrow cellularity and the pattern of lymphocyte infiltration were determined on core biopsy or aspirate clot specimens stained with H&E. Statistic The Fisher exact test was used to analyze differences between the T‐LGL and T‐LGL/other LPD groups. The median time from completion of last treatment with rituximab to the diagnosis of LGL disorder was 30 months.Results:LGL leukaemia or T‐LGL expansion were identified in the global group. Near total of the patient 21 (80.7%) had a direct history of a clonal B‐cell lymphocytosis, monoclonal B‐cell lymphocytosis (MBL), or clonal B‐cell disorder concomitantly with or shortly after the LGL diagnosis. The other predominant diagnosis was rheumatoid conditions in 9 patients (34.6%) (including Felty syndrome) and monoclonal gammopathy of unknown significance (MGUS) 7 patients (26.9%). The median age at the time of diagnosis was 68.5 years (range, 20‐86 years). B‐symptoms were reported by 4 (15.38%) patients, as well as Lymphadenopathy/splenomegaly was identified in 5 (19.23%). 4 individuals received treatment prior to the diagnosis of LGL, and the predominant treatment was methotrexate/rituximab. The favourite regimens in our daily practice were cyclosporin, rituximab or intermittent G‐CSF. The overall response rate at 3 months and complete response rate for the various treatments were as follows: steroids (11% and 3%), methotrexate (55% and 21%), rituximab (64% and 47%), cyclosporine (19% and 3%), respectively. All patients responded to rituximab after methotrexate treatment had failed. The mean number of treatments was 3.4 (range, 1‐5).Summary/Conclusion:Whether or not the T‐LGL and T‐LGL/other LPD groups are correlated with specific clinical‐biological features remains uncertain and is the subject of ongoing research. We don’t perform routinely in our clinical practice an investigation for the Constitutive activation of STAT3. In our series, we have not reported direct LGL‐related deaths.

PB2072 GENETIC MUTATION IN CYTOPENIC PATIENTS: DISTINCTIVE GENOMIC PROFILE BETWEEN PRECLINICAL VS. CLINICAL MYELODYSPLASTIC SYNDROME

Background: Myelodysplastic syndromes (MDS) are heterogeneous groups of clonal hematopoietic disorders. Diagnostic criteria of MDS is mainly based on morphologic assessment which remains a major diagnostic challenge due to individual variability among hematologists. Genetic mutations were identified in myelodysplastic syndrome but also found in cytopenic patients without dysplasia or non-significant dysplasia (preclinical MDS). Clinical utilities of genetic mutations were not clearly understood in preclinical MDS. We aimed to explore clinical implications of genetic mutations in preclinical MDS and compare with myelodysplastic syndromes. Secondary objective was to find association between degree of dysplasia and somatic mutations. Aims: We aimed to explore clinical implications of genetic mutations in preclinical MDS and compare with myelodysplastic syndromes. Secondary objective was to find association between degree of dysplasia and somatic mutations. Methods We enrolled patients with peripheral cytopenia ≥1 lineage (ANC < 1,800/mm3, hemoglobin < 10 gm/dL, platelet < 100 × 109/mL) with no other explainable causes of cytopenia. Bone marrow examinations were evaluated independently by 2 hematologists. If there were discrepant interpretations, cases would be reviewed by the third hematologist for final consensus. Bone marrow aspirations were evaluated as non-diagnostic marrow or dysplastic marrow using dysplasia cut-off of 10%. We extracted DNA from bone marrow and performed targeted sequencing by next generation sequencing (NGS) encompassing 143-gene panels. Results: Thirty-three patients were enrolled in this study. The median age at diagnosis was 71 years. Results of bone marrow examinations were categorized by morphology into 4 group, no dysplasia 15.1%, non-significant dysplasia (dysplasia < 10%) 9%, low risk MDS (IPSS-R ≤3.5) 51.5% and high-risk MDS (IPSS-R >3.5) 24.2%. Twenty-five from 33 cases (75.7%) harbored more than 1 somatic mutation. Twenty-six gene mutations were identified. Mutations were detected 2.18 mutation per 1 patient in average. Most frequent somatic mutations were TET2:9 (12.6%), ASXL1:6 (8.4%), TP53:6 (8.4%), RUNX1:6 (8.4%) and DNMT3A:5 (7%). The proportions of cases with somatic mutations were not different across the groups (no dysplasia 80%, non-significant dysplasia 100% and significant dysplasia 72%). According to mutation types in each group, mutations in epigenetic pathways were the most frequent mutations across all patient subgroups (preclinical 53%, low-risk MDS 38%, high-risk MDS 41%). Mutations in signaling pathway were predominated in preclinical MDS group 20% (no dysplasia and non-significant dysplasia) compare to MDS group (5% and 6% in low-risk and high-risk MDS, respectively) whereas mutations in transcription factor were predominated in MDS groups (33% and 29% in low-risk and high-risk MDS, respectively)compared to preclinical MDS group (7%). There was no difference between individual average frequency of gene mutations according to dysplasia subtype (P = 0.276). Higher variant allele frequency (VAF) of mutated genes was significantly observed in high risk MDS (45.3%) compared to low risk MDS (32%) and preclinical MDS (27.4%) (p = 0.003).Summary/Conclusion: In conclusion, molecular profiling was significantly different between preclinical MDS and MDS groups in terms of types of somatic mutations and VAF. This unique contrast could be used to distinguish between preclinical MDS and clinically significant MDS. In contrast, degree of marrow dysplasia was not associated with number of gene mutations in this study.

Overall Survival in Acquired Pure Red Cell Aplasia in Adults Following Immunosuppressive Therapy: Preliminary Results from the Nationwide Cohort Study (PRCA2016)

▪Background.Idiopathic PRCA and secondary PRCA not responding to the treatment of the underlying diseases are generally treated by immunosuppressive therapy. Because of the rarity of this disease, there are few reports regarding the long-term outcome following immunosuppression. We previously conducted the nationwide study for chronic PRCA in Japan that had been diagnosed between 1990 and 2006 across 109 institutions, and collected the data on a total of 185 patients (PRCA2004/2006 study). This study revealed that poor response to induction therapy and relapse of anemia were associated with death. There was no significant difference in survival between idiopathic and secondary PRCA in the PRCA2004/2006 study cohort.Objective.In order to identify the adverse risk factors for survival in acquired PRCA following immunosuppression in a prospective way, we have conducted another nationwide cohort study for acquired PRCA in adults (PRCA2016 study). The primary endpoint is the overall survival (OS) and the secondary endpoints include efficacy of immunosuppression, causes of treatment failure and survival times with iron-chelation therapy.Methods.This is designed as a prospective longitudinal observational study. Between 2006 and 2014, 554 PRCA patients were registered in the hematological disorder registry managed by the Japanese Society of Hematology. We sent the first questionnaires to the physicians asking for collaboration with this study and the responses showed the potential size of cohort was 181 patients (Fig. 1). We then sent the second questionnaires to collect data regarding underlying disease, laboratory findings including CBC and leukocyte differentials, results of bone marrow examination, immunological and cytogenetics, efficacy of immunosuppression, iron-chelation therapy in refractory cases and outcome. The review boards of participating institutions and the ethical committee of the JSH approved this study and informed consent was obtained from the patients.Results.As of June 16, 2018, 103 patients were registered in this study. Fifty-two patients were classified as having idiopathic PRCA and 51 patients as having secondary PRCA, including 16 thymoma- and 5 large granular lymphocyte (LGL) leukemia-associated PRCA. Seventy-one patients were treated with immunosuppressive agents. The response rates of cyclosporine, predonisolone, cyclophosphamide, azathioprine and combination with more than one immunosuppressants were 84% (43/51), 89% (8/9), 100% (2/2), 0% (0/1), 60% (9/15), respectively (Fig. 2). The Kaplan-Meyer estimates of the survival revealed that the estimated median survival time in idiopathic PRCA was 6,430 days and that in secondary PRCA has not yet been reached (Fig. 3). Survival time was not significantly different between the two subtypes of PRCA. Twenty-two deaths were reported and the major causes of death were infection and heart failure.Discussion/Conclusion.The most common subtypes of chronic PRCA in Japan were idiopathic, thymoma-associated and LGL leukemia-associated PRCA and this result was consistent with our observation in the PRCA2004/2006 study. Cyclosporine and prednisolone were frequently chosen for the induction therapy resulting in favorable responses. Preferential use of these two agents might reflect the physician's concern about the toxicity of the cytotoxic drugs. The median survival time of idiopathic PRCA was quite similar to the results in the previous cohort study. No significant difference in survival between idiopathic and secondary PRCA has been confirmed by the present study. These two cohort studies clearly indicate that novel diagnostic and predictive biomarkers should be developed to segregate the good and poor responders to immunosuppressive therapy in PRCA. [Display omitted] DisclosuresNakao:Novartis: Honoraria; Kyowa Hakko Kirin Co., Ltd.: Honoraria; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. Yonemura:Alexion Pharma: Honoraria, Research Funding. Matsuda:GlaxoSmithKline K.K.: Honoraria; Novartis Pharma K. K.: Honoraria; Chugai Pharmaceutical Co, Ltd.: Honoraria; Kyowa Hakko Kirin Co, Ltd.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; Celgene Corporation: Honoraria; Alexion Pharmaceuticals, Inc.: Honoraria; Sanofi K.K.: Honoraria; Beckman Coulter K.K.: Honoraria. Kurokawa:Otsuka Pharmaceutical: Research Funding; Astellas Pharma: Research Funding; MSD: Honoraria, Research Funding; Pfizer: Research Funding; Eizai: Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Research Funding; Teijin Pharma: Research Funding; Nippon Sinyaku: Honoraria, Research Funding; Takeda Pharmaceutical: Research Funding; Chugai Pharmaceutical: Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding. Arai:Novartis: Research Funding. Mitani:Kyowa Hakko Kirin Co., Ltd.: Consultancy, Research Funding, Speakers Bureau; Bristol-Myesr Squibb: Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Chugai: Research Funding; Astellas: Research Funding; Sumitomo Dainippon: Research Funding; Novartis: Research Funding; Toyama Chemical: Research Funding.

Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Numbers of early CD34+ progenitors of bone marrow hematopoiesis in patients with diffuse large B-cell lymphoma

To estimate the number of early progenitors of bone marrow (BM) hematopoiesis in patients with diffuse large B-cell lymphoma (DLBCL) in the late period after high-dose chemotherapy (HDCT) according to the mNHL-BFM-90 program. The investigators analyzed the results of BM immunophenotypic and histological studies in 40 patients (median age, 57 years) with DLBCL who received HDCT according to the mNHL-BFM-90 program at the Hematology Research Center (HRC), Ministry of Health of the Russian Federation (MHRF), in the period 2002 to 2009. A comparison group consisted of 19 patients (median age, 70 years) treated according to the CHOP/R-CHOP program at HRC, MHRF, in the same period. The median follow-up period was 6 years. The results of BM examination were analyzed before and 5-10 years after the end of HDCT. Immunophenotypic study determined the number of early CD34+ hematopoietic progenitors. BM cellularity, the size of erythroid, granulocytic and megakaryocytic lineages, their ratio, the presence of dysplasia signs, and secondary stromal changes were histologically determined. The BM toxic injury signs found for the first time were evaluated as manifestations of late myelotoxicity. At 5-to-10-year follow-ups after the end of HDCT according to the mNHL-BFM-90 program, the patients showed a smaller number of early CD34+ progenitors of BM hematopoiesis in 31 (78%) cases than those treated according to the CHOP/R-CHOP-21 program (n=8 (2%)) (p=0.005). Myelopoiesis with decreased CD34+ cell count was characterized by hypocellularity in 8 (26%) patients (p=0.07), the narrowing of megakaryocytic lineage in 14 (45%) (p=0.006), erythroid one in 7 (23%) (p=0.01), and granulocytic one in 8 (26%) (p=0.92), pronounced secondary stromal changes in 15 (48%) (p=0.03), and grade 1 thrombocytopenia in 13 (42%); p=0.02). There is evidence that the number of early CD34+ progenitors of BM hematopoiesis decreased in patients with DLBCL in the late period after HDCT. The investigation shows the relationship of the reduction in the number of early CD34+ progenitors of BM hematopoiesis in the late follow-up period to the presence of pronounced secondary changes in the BM stroma (p=0.02). There was no statistically significant relationship of the decreased number of CD34+ cells to the age younger or older than 60 years, to the period after the end of chemotherapy, to gender or presence of specific BM injury.

Extensive cutaneous necrosis in a 12-year-old girl: an unusual complication of secondary cold agglutinin syndrome.

Cold agglutinin syndrome (CAS) secondary to infection is rare, usually presenting with anaemia and minor skin changes. A 12-year-old girl with secondary CAS associated with extensive cutaneous necrosis is reported. She presented with fever and multiple necrotic lesions over both cheeks, the tip of nose, ear margins, hands and buttocks, along with pallor, hepatospenomegaly, acrocyanosis and gangrene of the fifth digit of the right hand. She had anaemia, unconjugated hyperbilirubinaemia and a positive direct antiglobulin test owing to cold agglutinins of the IgM type with anti-i specificity and titres of 1:512 at 4°C. Results of bone marrow examination were normal and cryoglobulins were negative. Cold antibodies released even during a brief, self-limited febrile illness can cause widespread cutaneous gangrene. We believe this is the first report in the paediatric age group.

Bone Marrow Staging For Lymphoma: A Re-Evaluation Of Clinical Utility

Bone marrow examination is an established component of the process used to stage patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical Hodgkin Lymphoma (CHL); and it is a general requirement of clinical trials. The procedure involves significant discomfort and inconvenience to the patient, as well as expense for the NHS, and this study was designed to evaluate the clinical utility of the information derived from staging bone marrow examinations. All patients presenting with DLBCL (n=1908), CHL (n=604) and FL (n=770) between 1st Sept 2004 and 31st August 2011 in the UK's population-based (3.6M) study area (Haematological Malignancy Research Network - www.hmrn.org) were included. Comprehensive clinical data, including diagnostic, prognostic, outcome and socio-demographic information are available for all patients. All diagnostic and staging specimens are reported in a single specialist haematopathology laboratory (the Haematological Malignancy Diagnostic Service – www.hmds.info). HMDS routinely undertake morphology and flow testing on bone marrow aspirate and trephine biopsies; while further molecular and cytogenetic tests are carried out at clinical discretion. This study aimed to assess the impact of bone marrow examination on the calculation of disease specific prognostic indices.Bone marrow examinations were performed in 85% of patients, providing morphological evidence of disease in 10.2% of DLBCL, 7.2% of CHL and 36.5% of FL. In 18 patients with DLBCL and 16 patients with CHL the bone marrow was the presenting site of disease and this was associated with a very poor clinical outcome. In DLBCL knowledge of the bone marrow result increased the IPI by 1 point in 4.0% and by 2 points in 1.1% of cases. Similarly, the Hasenclaver index increased by 1 point in 3.6% of CHLs and the FLIPI increased by 1 point in 9.0% of FLs. In the case of DLBCL, 70% of these patients had an IPI score of >2 before the results of the marrow examination were added. As well as the assessment of prognosis, the results of bone marrow examination are a component of a number of key clinical decisions. Patients with stage 1 FL are routinely treated with radiotherapy with curative intent. In the absence of a bone marrow result, an additional 27 patients would have potentially been treated with radiotherapy. The 5 year relative survival (corrected for underlying population mortality rates) of this group was similar to those with stage 2 disease on watch and wait, and was slightly inferior to that seen in true stage 1 disease. Similarly, patients with stage1A DLBCL may be treated with 3 courses of R-CHOP and radiotherapy in preference to 6 or 8 courses of R-CHOP alone. In our data , lack of knowledge of the bone marrow result would not have affected the classification of this group in. In DLBCL the decision to give prophylaxis to prevent CNS relapse may be based on 2 or more extranodal sites, including bone marrow, involved at presentation. In this group, this decision could have been affected in 51 cases.In the UK the approximate cost of taking and reporting a bone marrow is around $900. When used routinely the cost could approach $25,000 per patient whose IPI score is increased by the results of examination; the figure for CHL is $44,000. It is, therefore, difficult to justify the cost effectiveness of this approach. In newly presenting patients with lymphoma, bone marrow examination should be reserved for those with unexplained cytopenia, and those who may potentially require radiation therapy for early stage FL or CNS prophylaxis in DLBCL. Disclosures:Jack:Roche /Genentech: Research Funding. Off Label Use: Rituximab in Burkitts Lymphoma. Patmore:Roche: Consultancy, Honoraria.

Results of bone marrow examinations in patients with chronic immune thrombocytopenic purpura treated with eltrombopag

Abstract Abstract 1326 Poster Board I-348 BACKGROUND Bone marrow (BM) reticulin fibers can be increased in conditions such as neoplasms and autoimmune diseases (Frisch Haematol [Budap] 1982; Aharon Lupus 1997) and can lead to a clinical situation similar to osteomyelofibrosis. In healthy individuals, grade 1 and 2 reticulin have been reported in 27–70% and 4–20% of BM biopsies, respectively (Hultdin Med Onc 2007; Beckman Arch Path Int Med 1990; Bauermeister Am J Clin Path 1971). The presence of grade 1/2 reticulin was reported in the BM of up to 67% of patients with immune thrombocytopenic purpura (ITP) (Mufti J Supp Onc 2007). Theoretically, prolonged stimulation of megakaryocytes with TPO-R agonists might increase the risk of myelofibrosis (MF). Increased reticulin and peripheral nucleated RBCs have been reported in chronic ITP patients treated with romiplostim (Bussel Blood 2009). Eltrombopag, an oral, small molecule, TPO-R agonist, is approved in the United States for the treatment of chronic ITP. OBJECTIVE To determine whether eltrombopag treatment is associated with an increase in BM reticulin. METHODS Reports of BM biopsies performed prior to eltrombopag treatment were reviewed. In eltrombopag studies, complete blood counts (CBC) including white blood cell (WBC) differentials were performed at each visit. If a WBC differential indicated the presence of immature or dysplastic cells in the RAISE, REPEAT, and EXTEND studies, then a peripheral blood smear was performed. If the presence of immature or dysplastic cells on the blood smear was not consistent with the chronic ITP diagnosis, then a BM biopsy was performed. Additionally, a BM biopsy could be performed at any time at the investigator's discretion. In EXTEND, a BM biopsy was required after 1 year on treatment. Reticulin was quantified using the modified MF scale (Thiele Haematologica 2005). RESULTS Prestudy BM biopsies were available for 64/446 patients subsequently exposed to eltrombopag; 51 reports did not mention reticulin or fibrosis. Of the 13 remaining prestudy reports, 4 (31%) had increased reticulin. Ninety-one patients (5 patients RAISE; 86 patients EXTEND) had a BM biopsy following treatment initiation; none of the BM biopsies were prompted by an abnormal peripheral blood smear. In a 6-month placebo-controlled study (RAISE), 1 placebo-treated patient had an on-treatment BM examination that showed myelodysplastic syndrome, and 4 eltrombopag-treated patients (2 on-treatment and 2 posttreatment) had BM examinations. One patient treated with eltrombopag for 41 days had a posttreatment marrow examination that showed grade 2 (Bauermeister) reticulin. None of the 4 showed hematologically relevant BM alterations. In an open-label extension study (EXTEND), 86 patients treated for a median of 12 months (range: 1–18 months) at the time of the procedure had BM biopsies; 83 had mention of reticulin fibers in the report and were evaluable for this analysis. Five patients had MF grade 2 reticulin with no clinical signs or symptoms of BM dysfunction (eg, abnormal WBC differential or peripheral blood smear); 2 reported collagen. One patient had a biopsy 2 years prior to EXTEND (grade 1/3). After 15 months on study, a biopsy showed grade 2/3; this patient was withdrawn. Of note, while on treatment the patient was not considered a responder (platelets CONCLUSION There was no evidence of clinically relevant BM abnormalities or clinical findings typically associated with MF in patients treated for up to 18 months with eltrombopag. Systematic longitudinal evaluation of BMs in EXTEND will provide meaningful data regarding incidence of fibrosis during long-term treatment. Disclosures Saleh: GlaxoSmithKline: Speakers Bureau; Amgen: Speakers Bureau. Bussel: Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Research Funding; Sysmex: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees. Meyer: GlaxoSmithKline: Consultancy, Honoraria. Frederiksen: GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees. Johnni: GlaxoSmithKline: Employment. Aivado: GlaxoSmithKline: Employment. Brainsky: GlaxoSmithKline: Employment.

Results of Bone Marrow Examinations in Patients with Chronic Immune Thrombocytopenic Purpura Treated with Eltrombopag.

Abstract 1326Poster Board I-348 BACKGROUNDBone marrow (BM) reticulin fibers can be increased in conditions such as neoplasms and autoimmune diseases (Frisch Haematol [Budap] 1982; Aharon Lupus 1997) and can lead to a clinical situation similar to osteomyelofibrosis. In healthy individuals, grade 1 and 2 reticulin have been reported in 27–70% and 4–20% of BM biopsies, respectively (Hultdin Med Onc 2007; Beckman Arch Path Int Med 1990; Bauermeister Am J Clin Path 1971). The presence of grade 1/2 reticulin was reported in the BM of up to 67% of patients with immune thrombocytopenic purpura (ITP) (Mufti J Supp Onc 2007). Theoretically, prolonged stimulation of megakaryocytes with TPO-R agonists might increase the risk of myelofibrosis (MF). Increased reticulin and peripheral nucleated RBCs have been reported in chronic ITP patients treated with romiplostim (Bussel Blood 2009). Eltrombopag, an oral, small molecule, TPO-R agonist, is approved in the United States for the treatment of chronic ITP. OBJECTIVETo determine whether eltrombopag treatment is associated with an increase in BM reticulin. METHODSReports of BM biopsies performed prior to eltrombopag treatment were reviewed. In eltrombopag studies, complete blood counts (CBC) including white blood cell (WBC) differentials were performed at each visit. If a WBC differential indicated the presence of immature or dysplastic cells in the RAISE, REPEAT, and EXTEND studies, then a peripheral blood smear was performed. If the presence of immature or dysplastic cells on the blood smear was not consistent with the chronic ITP diagnosis, then a BM biopsy was performed. Additionally, a BM biopsy could be performed at any time at the investigator's discretion. In EXTEND, a BM biopsy was required after 1 year on treatment. Reticulin was quantified using the modified MF scale (Thiele Haematologica 2005). RESULTSPrestudy BM biopsies were available for 64/446 patients subsequently exposed to eltrombopag; 51 reports did not mention reticulin or fibrosis. Of the 13 remaining prestudy reports, 4 (31%) had increased reticulin. Ninety-one patients (5 patients RAISE; 86 patients EXTEND) had a BM biopsy following treatment initiation; none of the BM biopsies were prompted by an abnormal peripheral blood smear. In a 6-month placebo-controlled study (RAISE), 1 placebo-treated patient had an on-treatment BM examination that showed myelodysplastic syndrome, and 4 eltrombopag-treated patients (2 on-treatment and 2 posttreatment) had BM examinations. One patient treated with eltrombopag for 41 days had a posttreatment marrow examination that showed grade 2 (Bauermeister) reticulin. None of the 4 showed hematologically relevant BM alterations. In an open-label extension study (EXTEND), 86 patients treated for a median of 12 months (range: 1–18 months) at the time of the procedure had BM biopsies; 83 had mention of reticulin fibers in the report and were evaluable for this analysis. Five patients had MF grade 2 reticulin with no clinical signs or symptoms of BM dysfunction (eg, abnormal WBC differential or peripheral blood smear); 2 reported collagen. One patient had a biopsy 2 years prior to EXTEND (grade 1/3). After 15 months on study, a biopsy showed grade 2/3; this patient was withdrawn. Of note, while on treatment the patient was not considered a responder (platelets <50,000/μL) but did have decreased bleeding. The second patient was 81 years old with a history of 3 cancers. A similar degree of reticulin was observed when comparing the biopsy taken 6 years prior to EXTEND and after 14 months on study, but collagen was noted on the second BM. A patient with MF grade 1 reticulin reported collagen, but did not experience any adverse event or significant change in CBC and is continuing on study with good platelet response. CONCLUSIONThere was no evidence of clinically relevant BM abnormalities or clinical findings typically associated with MF in patients treated for up to 18 months with eltrombopag. Systematic longitudinal evaluation of BMs in EXTEND will provide meaningful data regarding incidence of fibrosis during long-term treatment. DisclosuresSaleh:GlaxoSmithKline: Speakers Bureau; Amgen: Speakers Bureau. Bussel:Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Research Funding; Sysmex: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees. Meyer:GlaxoSmithKline: Consultancy, Honoraria. Frederiksen:GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees. Johnni:GlaxoSmithKline: Employment. Aivado:GlaxoSmithKline: Employment. Brainsky:GlaxoSmithKline: Employment.

Die Rationale für Knochenmarkuntersuchungen bei Patienten mit entzündlich-rheumatischen Erkrankungen

Inflammatory rheumatic diseases and the applied immunosuppressive treatments can lead to bone marrow depressions and promote hematologic malignancies. Our objective was to explore indications for and results of bone marrow examinations in a large cohort. Between 1990 and 2004 146 bone marrow examinations in 3638 patients were performed due to abnormal laboratory results. Medical history, results of bone marrow examination (morphology, histology) and cytogenetic data were investigated retrospectively. Patients' (67.8% female) mean age at bone marrow examination was 53.5 years (SD 15.5), median disease duration 2.9 years. Indications for bone marrow examination were changes in peripheral blood counts in 81.7%. In 52 patients (35.6%) clinically relevant, partially neoplastic bone marrow changes (5 non-Hodgkin lymphoma, 9 myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) and 3 myeloproliferative neoplasias) were evident. Medication history showed intake of hydroxy-/chloroquine (13.5%), methotrexate (17.3%), cyclosporin (7.7%), sulfasalazine (7.7%), mycophenolatmofetil, gold, leflunomide (each 1.9%), azathioprine (aza, 25.0%) or cyclophosphamide (cyc, 7.7%) prior to bone marrow examination. 7 out of 9 patients, who developed MDS/AML had been treated with either azathioprine alone or additionally with cyclophosphamide (n = 3). One third of our patients showed relevant bone marrow changes that might be associated to therapy. The risk seems to be increased especially in patients with inflammatory rheumatic diseases who had received azathioprine alone or in combination with cyclophosphamide. Health care providers should bear in mind the risk of hematologic malignancies and monitor patients closely in this respect. Bone marrow examination should be performed in case of changes in peripheral blood counts; especially clinically relevant anemia, granulocytes < 2,500/microl, thrombocytes < 100,000/microl and relevant changes over time should lead to bone marrow examinations.

A Randomized Trial Comparing Individualized Vs. Non-Individualized Treatment for Elderly Acute Myeloid Leukemia: JALSG GML200 Study

The outcome of elderly patients with acute myeloid leukemia (AML) has not been improved for these three decades, although the incidence is getting increased with the aging of the population in Japan. In the JALSG GML200 study, we prospectively registered all elderly patients with AML during this study irrespective of the eligible criteria,. Since elderly patients are less able to tolerate to intensive cyottoxic intensive chemotherapy, we conducted a randomized study to assess an individualized induction treatment. After consolidation chemotherapy, we evaluated the adjuvant effect of ubenimex (UBX), an anti-leukemia immunomodulator.Method: From April 2000 to August 2005, the JALSG GML200 study registered all newly diagnosed AML patients aged 65 years and over. Patients who satisfied the eligibility criteria were randomized to receive either the individualized therapy (arm B) or non-individualized therapy (arm A). Patients who were not eligible were classified in arm C.Induction therapy of Arm A: enocitabine (BH-AC) 200 mg/m2 on days 1–8, 3 h infusion + daunorubicin (DNR) 40 mg/m2 on days 1–3, 30 min infusion. Arm B: BH-AC 200 mg/m2 on days 1–8, with extension to day 12 according to the results of bone marrow examination on days 7 and 10, + DNR 40 mg/m2 on days 1–3, with extension on day 12 depending on the results of bone marrow examination on days 7 and 10. Patients who achieved a complete response (CR) were randomized again to receive immuno-therapy with ubenimex (group UY) or without ubenimex (group UN). Consolidation therapy consisted of three courses:BH-AC 200 mg/m2 on days 1–5 + Mitoxantrone (MIT) 7 mg/m2 on days 1–3,BH-AC 200 mg/m2 on days 1–5 + DNR 30 mg/m2 on days 1–2, ETP 100 mg/m2 on days 1–3,BH-AC 200 mg/m2 on days 1–5 + ACR 14 mg/m2 on days 1–5.Result: Of the 374 patients registered, 244 patients were eligible for randomization to arms A and B, and 235 patients were evaluable. The median patients' age of arms A, B and C were 70 (range, 65–79), 71 (range, 65–79), and 74 years (range, 65–92), respectively. CR rate of arm A was 63.2% and that of arm B was 65.3% (p = 0.75). CR rates of male and female patients significantly differed in each arm (arm A: male 55.4% vs. female 76.3%, p=0.053, arm B: male 53.1% vs. female 80.0%, p=0.008). Overall survival rates at 3 years of arms A and B were 25.5% and 21.5% (p = 0.56), respectively. With reference to survival with or without ubenimex in patients who achieved CR, the overall survival rate at 3 years was 43.1% for arm UY and 26.9% for arm UN (p=0.073). The number of patients in arm C was 130, and most patients in this arm received similar induction chemotherapy using DNR and BH-AC. The survival rate of this group at 3 years was unexpectedly high at 29.4%.Conclusion: Induction chemotherapy using DNR and BH-AC is one of the superior methods to achieve CR in elderly AML patients. However, individualized treatment has little advantage over non-individualized therapy. The remission rate of the female patients is higher than male patients, and it may have relations with a long life span of the Japanese female. Long-term survival rate is still unfavorable and search for a better post-remission therapy is warranted. Immunomodulator therapy using ubenimex provides a possible benefit for longer survival in elderly AML patients at CR.

Results of bone marrow examination in 275 patients with histological features that suggest an indolent type of cutaneous B‐cell lymphoma

Whether or not bone marrow biopsies should be performed routinely in patients with skin lesions that show histological features consistent with an indolent B-cell lymphoma [marginal zone lymphoma (MZL) or follicle centre lymphoma (FCL)] has been debated. As no studies have addressed this question for this group of lymphomas, we evaluated the results of bone marrow biopsy examination in 275 patients with histological features consistent with MZL (n = 82) or FCL (n = 193) first presenting in the skin. In the MZL group, two of 82 patients (2%) showed bone marrow involvement, which was the only extracutaneous localization in one of these patients. In the FCL group, 22 of 193 patients (11%) had bone marrow involvement and was the only extracutaneous localization in nine of them. FCL patients with skin lesions and a positive bone marrow had a significantly worse prognosis when compared with patients with only skin lesions (5-year disease-specific survival 63% vs. 95%; P = 0.001). These results indicate that bone marrow investigation is essential for staging patients with a FCL first presenting in the skin. Bone marrow examination appears to have limited value in patients with MZL presenting in the skin.

Revisited indications for bone marrow examinations in HIV-infected patients.

We reviewed the indications for and the results of bone marrow examination (BME) from HIV-infected patients as an attempt to improve its diagnostic yield. One-hundred-and-eight bone marrow specimens from 90 patients during a 3-year period were examined. A cytological, histological and microbiological study was carried out on the specimens. Forty-three evaluable examinations (40% of total) performed for cytopenia showed normo- or hypercellularity in 33 (77%). Fifty bone marrow specimens were cultured for mycobacteria with a yield of 42% when the indication was persistent fever. Positive cultures yielded Mycobacterium avium complex in 8 out of 12 patients. Twenty-seven patients had both culture and biopsy; granulomas were associated with all the positive (10/10) and with 1 out of 17 negative cultures (chi-square test: p < 0.001). A bone marrow involvement with lymphoma was found in 2 out of 6 patients with previously diagnosed lymphoma, and biopsy revealed a lymphoma in 2 patients. Morphological bone marrow examination should be associated with other techniques in order to appreciate bone marrow production. Bone marrow biopsy is useful for the investigation of persistent fever since granulomas suggestive of disseminated mycobacteria are frequent and allow a treatment to be initiated before microbiological confirmation and antibiotic susceptibility test.

A clinicopathologic study of ten patients with recurrent unexplained flushing

We describe the clinicopathologic features of 10 patients with recurrent unexplained flushing. These patients were referred to the National Institutes of Health with a diagnosis of mastocytosis or idiopathic anaphylaxis. Both diagnoses were eliminated after evaluation. Patients reported attacks of flushing lasting 15 minutes to 2 days and associated with such symptoms as anxiety, chest tightness, paresthesia, slurred speech, weakness, and pruritus. Abdominal pain was a constant feature, often associated with cramping and an increase in stool frequency. Attacks witnessed by physicians consisted of an exaggerated blush response of the face and upper part of the chest, and were sometimes associated with tachycardia, mild hypertension, and tachypnea. Hives, angioedema, wheezing, and hypotension were not observed. Routine laboratory studies and 5-hydroxyindoleacetic acid, vanillylmandelic acid, and plasma histamine levels were normal. Plasma histamine levels did not elevate during attacks. When performed, results of bone marrow examinations, skin biopsies, and bone scans were normal. Psychiatric examinations frequently revealed somatization disorders. Patients had often been prescribed a wide variety of medications including antihistamines, nonsteroidal anti-inflammatory drugs, and steroids, with little or no benefit. Despite the benign nature of the clinical and laboratory findings, patients had undergone repeated, often invasive, examinations for several years. Whether such patients have a prominent flush response exaggerated through a somatization disorder or a relatively benign flushing disorder associated with putative mediator release remains to be determined. Recognition of this category of patients with unexplained flushing will avoid subjecting such patients to unwarranted repeated examinations, procedures, and inappropriate therapy.

Expression of leukocyte adhesion molecules (ICAM-1/LFA-1) related to clinical behaviour in B cell lymphomas.

We investigated the expression of adhesion molecules of lymphocyte function-associated antigen-1 alpha (LFA-1 alpha) and its ligand intercellular adhesion molecule-1 (ICAM-1) on 74 well-characterized B cell lymphomas. The LFA-1 was expressed on B cell lymphomas (21/74; 28 per cent), but to a lesser degree than ICAM-1 which was highly expressed (48/74 cases; 64 per cent). From the results of bone marrow examination of 39 cases with B cell lymphomas, 13 of 16 cases with a lack of ICAM-1 molecule showed a higher incidence of marrow involvement, but nine of 23 cases with the expression of ICAM-1 molecule showed a lower incidence. These findings suggest that the lack of expression of the ICAM-1 molecule by B cell lymphomas correlates with bone marrow involvement by lymphoma cells (p < 0.05). Expression of the LFA-1 molecule appears not to correlate with marrow involvement (p < 0.05).

A computer-based reporting system for bone marrow evaluation.

A computerized system of reporting results of bone marrow examination has been implemented at The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, since 1975. All results are entered via the keyboard of cathode-ray tube (CRT) consoles and are instantly available to the attending physician in CRTs strategically located throughout the institution in patient-related areas. Differential counts are available within two to three hours after aspiration. Description of clot sections and smear, diagnosis, and differential diagnosis are completed within 24 hours. Permanent reports are also printed by the computer at regular intervals during the day. The physician can ask the computer for results on a given day or for a cumulative summary displayed in tabular or plot form. This system has proven efficient and rapid, not only for direct reporting of bone marrow examination results but also for storage and retrieval of patient information.