Pattern Of Bone Marrow Involvement Research Articles

Evaluation of the Findings of Peripheral Blood Smear, Bone Marrow Aspiration and Biopsy, Iron Storage, and Immunophenotype in Patients with Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults with various signs, symptoms, and types of progression. In this study, we have investigated the frequency and correlation of laboratory findings including peripheral blood smear, bone marrow aspiration and biopsy, and cellular immunophenotyping in CLL patients. In this cross-sectional and retrospective study, the laboratory information of all 161 patients with definite diagnoses of CLL was extracted, and the frequency and correlation between different laboratory data were analyzed by descriptive statistics methods and Jamovi software version 2022. Demographic factors such as age and gender, and laboratory factors such as anemia, thrombocytopenia, white blood cell count, percentage of lymphocytes, and patterns of bone marrow involvement were evaluated for 161 patients. There was a significant relationship between the bone marrow iron storage and the percentage of FMC7 marker expression with the percentage of atypical lymphocytes in the peripheral blood. Chronic lymphocytic leukemia, a prevalent form of leukemia associated with substantial mortality and morbidity, can be detected through a range of diagnostic techniques. Analyzing the results of these diagnostic tests and examining the prevalence of these indicators in patients afflicted with the condition can prove highly beneficial for prompt disease diagnosis, and prognosis determination among affected individuals.

Pattern of Bone Marrow Involvement in B-cell Non-Hodgkin's Lymphoma - Experience from a Tertiary Care Center in North India

Pattern of Bone Marrow Involvement in B-cell Non-Hodgkin's Lymphoma - Experience from a Tertiary Care Center in North India

CLL-037 The Pattern of Bone Marrow Involvement Among Chronic Lymphocytic Leukemia Patients and Its Impact on the Disease Outcome in Kurdistan Region of Iraq

There are variable degrees of bone marrow (BM) infiltration patterns in chronic lymphocytic leukemia (CLL). Four BM patterns, interstitial, nodular, mixed, and diffuse patterns, were identified. The aim of this study is to assess the effects of BM infiltration patterns on the disease outcome among CLL patients in the Kurdistan Region of Iraq. This study is a cross-sectional, descriptive, retrospective that involved 106 patients with CLL disease. The data were collected from cancer centers in the Kurdistan region of Iraq (including Erbil, Sulaymaniyah, and Duhok) from January 1, 2010 to December 31, 2019. BM histopathology study of all patients was assessed and correlated with the disease outcome. Fifty-three (50.0%) patients had interstitial BM patterns, 17 (16.0%) had nodular BM pattern, 14 (13.2%) had mixed BM patterns, and 22 (20.8%) had diffuse BM pattern. The results showed that patients with interstitial, nodular, and mixed BM patterns had a superior overall survival (OS) and progression-free survival (PFS) rate than diffuse BM pattern. Kaplan-Meier curve illustrates that our CLL patients with interstitial BM patterns had a better mean OS rate (44.0 months) than diffuse BM pattern with a mean of (23.2 months). As well as for PFS, the mean was (35.7 months) for the interstitial BM patterns and (17.6 months) for diffuse BM pattern. We demonstrate that the BM involvement patterns have a prognostic value in our CLL patients and provide more reliable information regarding the clinical outcome.

Purine Nucleoside Analogs Plus Rituximab Is an Effective Treatment Choice for Hairy Cell Leukemia-Variant: Results from a Single Center in China

Background: Hairy cell leukemia-variant (HCL-v) is one type of chronic lymphocytic proliferative disorders which was classified into splenic B-cell lymphoma/leukemia, unclassifiable. Both clinical and laboratory characteristics and treatment strategy remain elusive due to the rarity of the disease. Here, we firstly presented the diseases features and efficacy of a variety of treatment options in a large cohort from China.Methods: Thirty-three patients were diagnosed with HCL-v in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College from June 1990 to February 2021. We analyzed the disease characteristics and treatment outcome, especially in terms of clinical manifestation, immunophenotypic and molecular evaluation and efficacy of multiple first-line treatment.Results: The median age of this cohort was 59 years (range, 34-79 years) at diagnosis, with 23 males and 10 females. Abdominal mass and relative signs (n=22) and abnormal complete blood count (n=9) were the most common chief complaints. Splenomegaly was present in 32 (97.0%) cases, among whom 26 (78.8%) cases were massive. Leukocytosis and leukopenia were presented in 23 (69.7%) patients and 5 (15.2%) patients, with a median white blood cell count of 21.58×10 9/L (range, 1.34-224.59×10 9/L). The median percentage of the leukemic cells in bone marrow tested by flow cytometry was 33% (range, 6.2%-96%), and immunophenotyping showed monoclonal B-cells positive for pan B-cell antigens (CD19, CD20, CD22, CD79b) in almost all patients (Table). CD11c was positive in all patients, and CD103 was positive in 20/26 (76.9%) patients. CD25 was negative in 30/33 (90.9%) patients, and CD23 was negative in 20/26 (76.9%) cases. CD200 was frequently expressed among patients (15/21, 71.4%). For the pathological pattern of bone marrow involvement, 20/27 (74.1%) patients showed a predominantly interstitial pattern. Moreover, Annexin A1 was negative in all (n=12) patients detected by immunohistochemistry. Conventional cytogenetic analysis showed abnormal karyotype in 10/24 (41.7%) patients, including 6 patients with complex karyotype. Fluorescence in situ hybridization analysis showed deletion of TP53 in 4/20 (20.0%) patients and IGH translocation in 5/16 (31.3%) patients. The BRAF V600E mutation was negative in all the patients (n=20). In 2 of 14 (16.7%) patients, TP53 mutation was detected by next-generation sequencing. Sixteen of nineteen (84.2%) patients showed monoclonal IGHV rearrangements, and the most common rearrangement fragment was VH4-34 (n=3, 18.8%). Six of seventeen (35.3%) patients presented with unmutated IGHV and patients with VH4-34 were all unmutated. 31 patients needed treatment finally. Treatment choices included interferon-α (IFN-α) in 11 patients, chlorambucil (CLB) in 5 patients, single purine nucleoside analogs (PNA) in 3 patients and PNA plus rituximab in 9 patients. Four patients who received IFN-α or CLB treatment also underwent splenectomy. The objective response rate was 100% for patients receiving PNA plus rituximab and 77% for cases receiving others. And people treated with PNA plus rituximab had a higher complete response rate compared to the other regimen (75% versus 12%, P = 0.004). During a median follow-up of 32 months (range, 3-207) for 29 patients, 14 (48.3%) patients experienced at least one relapse or progression, and 7 (24.1%) patients had 2 or more relapses. Of note, one case also underwent a diffuse large B-cell lymphoma transformation. The median PFS and OS were 31 months (95% CI 25.5-36.5) and 70 months (95% CI 50.5-89.5), respectively. PNA plus rituximab prolong PFS compared to the others (3-year PFS rate 80% [95%CI 20-97] versus 10% [95%CI 1-35], P = 0.012, Figure A). But no significant difference in 3-year OS rate was observed between two groups (100% [95%CI 100-100] versus 43% [95%CI 10-73], P = 0.128, Figure B).Conclusion: HCL-v is a rare disease with specific clinical and immunophenotypic features but may overlap with classic hairy cell leukemia or other splenic B-cell neoplasms. Overall, it is an indolent lymphoma with recurrent progression, and the use of PNA plus rituximab in first-line treatment can result in a deeper and longer remission. [Display omitted] DisclosuresWang: AbbVie: Consultancy; Astellas Pharma, Inc.: Research Funding.

The pattern of bone marrow involvement among chronic lymphocytic leukemia patients and its impact on the disease outcome in Kurdistan Region of Iraq

OBJECTIVES : There are the variable degrees of bone marrow (BM) infiltration patterns in chronic lymphocytic leukemia (CLL). Four BM patterns: Interstitial, nodular, mixed, and diffuse patterns were identified. The aim of this study is to assess the effects of BM infiltration patterns on the disease outcome among CLL patients in Kurdistan Region of Iraq.METHODS: This study is a cross-sectional, descriptive, retrospective involved 106 patients with CLL disease. The data are collected in the Kurdistan region of Iraq (including Erbil, Sulaymaniyah, and Duhok) cancer centers. Through the period from January 1, 2010 to December 31, 2019. BM histopathology study of all patients was assessed and correlated with the disease outcome.RESULTS: Fifty-three (50.0%) patients had interstitial BM patterns, 17 (16.0%) had nodular BM pattern, 14 (13.2%) had mixed BM patterns, and 22 (20.8%) had diffuse BM pattern. The results showed that patients with interstitial, nodular, and mixed BM patterns had a superior overall survival (OS) and progression-free survival (PFS) rate than diffuse BM pattern. Kaplan–Meier curve illustrates that our CLL patients with interstitial BM patterns had a better mean OS rate (44.0 months) than diffuse BM pattern with a mean of (23.2 months). As well as for PFS, the mean was (35.7 months) for the interstitial BM patterns and (17.6 months) for diffuse BM pattern.CONCLUSIONS: We demonstrate that the BM involvement patterns have a prognostic value in our CLL patients and provide more reliable information regarding the clinical outcome.

Original Article Non-Hematological Malignancies Seeding in Bone Marrow

Background: Bone marrow is the site of origin for primary haematological malignancies and is the third common preferred site metastasized by the solid tumors. The malignant infiltration of the hematopoietic tissue alters the clinical course of disease, response of the treatment and influences the overall survival. The aim of this study was to assess pattern of bone marrow involvement by different solid tumors and their correlation with hematological parameters.
 Methods: In this retrospective study, 8064 bone marrow examinations from Jan 2011-Aug 2017 at tertiary health and research centre of Northern India were evaluated to access spectrum of different solid tumors infiltrating the bone marrow alongwith their clinical, hematological and histopathological findings.
 Result: Total 38 cases of non-hematological malignancies metastasizing to bone marrow were evaluated with main indications of lytic lesions, cytopenia and Pyrexia of Unknown Origin. The most common metastasis were adenocarcinoma of prostate and lung. In 33 cases, the clinical, cytomorphological and immunohistochemical analysis findings were correlated to know primary site, while in remaining five patients, even after complete diagnostic evaluation, the definitive origin could not be ascertained, therefore categorized as Carcinoma of Unknown Primary Site (CUPS).
 Conclusion: Our series showed that anemia as commonest parameter, followed by leukopenia, thrombocytopenia. Many cases were misdiagnosed as multiple myeloma due to lytic lesion, anemia and hypercalcemia. We concluded that unexplained cytopenia are strong indicators of bone marrow examination; an easy, convenient, sensitive, effective procedure of staging of tumor, monitoring the course and prognosis of solid tumors.

Genomic and Immunophenotypic Landscape of Aggressive NK-Cell Leukemia.

Aggressive natural killer-cell leukemia (ANKL) is a rare, lethal disease with pathologic features that are underdescribed in the literature, particularly in Western nations. In addition, although data on the molecular pathogenesis of ANKL has been reported, evaluation of such data in a clinicopathologic context remains limited. Patients diagnosed with ANKL were identified retrospectively. Detailed demographic and clinicopathologic data were analyzed. We assessed novel markers by immunohistochemistry and performed targeted next-generation sequencing analysis. The study group included 9 men and 3 women with a median age at diagnosis of 47.5 years (range, 20 to 75 y). Two distinct patterns of bone marrow involvement were identified: interstitial and sinusoidal. The neoplastic cells were positive for CD56 and CD94, and negative for surface CD3, CD5, and CD57 in all cases assessed. They were also positive for CD2 (10/12), c-MYC (6/8), BCL2 (6/8), CD16 (5/7), EBER (9/12), CD7 (6/11), pSTAT3 (3/8), CD8 (2/6), PD-L1 (2/8), CD4 (2/11), CD8 (2/6), and CD158 (1/5). Aberrant p53 expression was identified in most (7/8) cases; p53 was strongly expressed in 4 cases. Conventional cytogenetic analysis showed clonal abnormalities in 5 of 12 cases. TP53 mutations were detected in 3 of 6 cases, whereas ASXL1 and TET2 mutations were each detected in 2 of 6 cases. Patients had very poor outcomes despite intensive chemotherapy, with a median survival of 2 months. ANKL exhibits 2 distinct patterns of tissue involvement. Neoplastic cells in ANKL are commonly positive for c-MYC and EBER, and they have a high frequency of p53 overexpression, frequently with corresponding TP53 mutations.

Analysis of Bone Marrow and Peripheral Blood Film findings in sixty diagnosed cases of Lymphoma

Lymphoma constituting 55.6% of hematological malignancy, its prognosis depends on the correct diagnosis and stage of the disease, which is established after examination of peripheral blood film (PBF), bone marrow aspiration (BMA) and bone marrow biopsy (BMB) along with other parameters. The objective is to find out the percentage and pattern of bone marrow involvement, along with peripheral blood changes in lymphoma. PBF, BMA and BMB findings studied in 60 lymphoma patients during a period of 3 years. The PBF and aspiration smears stained with Leishmann’s stain, while the trephine biopsy processed and stained with Haematoxylin and eosin (H & E) stain and Reticulin stain. The results were scrutinized, compared and evaluated. The male to female ratio was 1.4:1, including 53(88.3%) cases of NHL and 7(11.7%) cases of HL. Most common age group involved in NHL was 51-60 years and in HL was 31-40 years. 19/60 (31.7%) cases showed leucocytic lymphocytosis on PBF examination. Percentage lymphocytes in marrow differential count was increased in 16(26.7%) cases and were reported with bone marrow involvement on BMA and BMB and 1 case having borderline percentage lymphocyte count on BMA was reported as bone marrow involved case, only after examining the BMB. The diffuse pattern of involvement was most common in 7(41.2%), followed by paratrabecular pattern in 6(35.3%) cases. Thus to conclude bone marrow examination give valuable information in lymphoma, about disease burden, percentage of involvement, pattern of involvement and baseline involvement prior to therapy.

Pattern of Bone Marrow Involvement by Solid Tumors: Experience from a Tertiary Care Center from South India

Abstract Background: Bone marrow involvement by solid tumor implicates advanced disease and dismal prognosis. Bone marrow aspiration and biopsy are routinely performed as staging workup for certain small round cell tumors and also for unexplained cytopenia in other solid tumors. It is important to rule out bone marrow involvement before planning for curative treatment. Materials and Methods: This was a retrospective observational study. The aim of our study was to evaluate the pattern of bone marrow involvement by different solid tumors and their correlation with the hematological abnormalities. We retrospectively evaluated bone marrow aspirations and biopsy performed in past 3 years. Results: At our institution, bone marrow examinations were performed in 440 patients during past 3 years for solid malignancies. Out of 440, 206 were pediatric cases and 234 were adult cases. Bone marrow was involved in 56 (12.7%) patients. Among the pediatric cases, bone marrow involvement was present in 30 (12.8%) cases, and in adult cases, bone marrow was involved was in 26 (11.1%) cases. Neuroblastoma (40%) was the most common malignancy, which involved the bone marrow among pediatric cases, followed by retinoblastoma (26.6%) and Ewing’s sarcoma (20%). Among adult patients, neuroendocrine carcinoma (23%) was at the top of the list of tumors involving bone marrow, which is followed by Ewing’s sarcoma (19.2%) and nasopharyngeal carcinoma (11.5%). Conclusion: Neuroblastoma and neuroendocrine carcinoma are the major cause of bone marrow involvement among the solid malignancies in pediatric and adult population, respectively. Use of immunohistochemistry markers on bone marrow biopsies may result in higher detection rate.

Examining the Clinical Heterogeneity of Smoldering Multiple Myeloma

Examining the Clinical Heterogeneity of Smoldering Multiple Myeloma

Pattern of bone marrow involvement in non Hodgkin's lymphoma classified according to WHO classification: Report of a developing country Pakistan.

BACKGROUND:Limited information is available from developing countries in patients of non-Hodgkin's lymphoma (NHL). Hence, we reviewed the demographical profile along with bone marrow infiltration pattern in patients with NHL presented at Liaquat National Hospital and Medical College.MATERIALS AND METHODS:In this descriptive study, adult patients with NHL were enrolled from January 2011 to December 2015.RESULTS:One hundred and Eighty-four histopathologically confirmed cases of NHL were identified. There were 139 males and 45 females, with a male-to-female ratio of 3:1. The mean age was 48.5 ± 16.0 years with the median age of 50 years. B-symptoms were present in 80.4% of patients. Lymph node enlargement was present in 71.1% of the cases. One hundred and sixty-eight patients had B-cell lymphoma (91.3%) and 16 patients had T-cell lymphoma (8.6%). Overall 158 (85.8%) patients had aggressive lymphoma. The frequency of bone marrow infiltration in our NHL patients was found to be 31.5%. Pattern of infiltrate was diffuse (14.6%) predominantly followed by interstitial (6.5%) and paratrabecular (5.4%) types of infiltration. The least common was nodular infiltrate accounted in 9 (4.8%) patients.CONCLUSIONS:B-cell lymphoma is more frequent than T-cell lymphoma. Younger age, aggressive lymphoma, and predominance of B-symptoms are more frequently seen. Diffuse bone marrow infiltration is more common in our set up probably because of a relatively late presentation in our patients.

Correlation of Patterns of Bone Marrow Infiltration and Biochemical factors in Non-Hodgkin Lymphoma.

Objectives:To investigate the patterns of bone marrow involvement in in Non-Hodgkin’s Lymphoma (NHL) patients and to correlate the patterns with β2 microglobulin (β2m) and lactate dehydrogenase 2 (LD2) levels in these patients.Methods:It was a cross sectional study which was conducted in two years at Post Graduate Medical Institute, Lahore and at Centre of Excellence in Molecular Biology (CEMB), Lahore. The study was conducted on 50 subjects irrespective of age and sex divided into two groups i.e. Group-A comprising 20 normal healthy controls while Group-B consisted of 30 patients of NHL with bone marrow infiltration. Bilateral bone marrow trephine biopsy was done to assess the patterns of bone marrow infiltration. Serum β2m and LD2 isoenzyme levels were determined in already diagnosed 30 patients of NHL. The values were compared with 20 healthy age and sex matched controls. Correlation coefficients were determined using Pearson’s Correlation Coefficient. The estimations were made prior to the institution of chemotherapy.Results:β2m and LD2 levels were significantly (p-Value < 0.05) raised in NHL patients with disease advancement and were compared with controls. These serological markers showed negative correlation (-0.235 for β2m and -0.133 for LD2) with the spread of disease and patterns of involvement in NHL patients.Conclusion:By observing the patterns of bone marrow involvement in NHL patients possible guidelines about prognosis and treatment protocols can be obtained as the serological markers levels correlate well with the spread of disease and patterns of involvement in NHL patients.

Diagnostic Evaluation of Patterns of Bone Marrow Involvement in Myelophthisic Anemias

Diagnostic Evaluation of Patterns of Bone Marrow Involvement in Myelophthisic Anemias

Proliferation centers in bone marrows involved by chronic lymphocytic leukemia/small lymphocytic lymphoma: a clinicopathologic analysis.

Proliferation centers (PCs) are a characteristic finding in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) lymph nodes, and their presence and extent in this site are not currently felt to be related to clinical course. In contrast, detailed clinicopathologic analyses of bone marrow (BM) PCs have not been previously reported. The PCs in 88 CLL/SLL BMs from 45 patients (pts) were graded (0-4) and were correlated with other morphologic, immunophenotypic, cytogenetic, and laboratory features. Proliferation centers were present in 69 BMs (78%) from 32 pts (71%) and were distinct/prominent (grades 2-4) in 21 pts (47%), with the latter more commonly found in follow-up BMs (1/7 diagnostic BMs vs 49/81 follow-up BMs; P=.04). When present, PCs were most commonly graded as distinct nodules easily visible on ×10. No relationships were identified between PCs and any complete blood count parameter, serum lactate dehydrogenase or IgG levels, degree or pattern of BM involvement, blood morphology, CD38 and FMC7 expression by flow cytometry, or fluorescence in situ hybridization results, when the first encountered BM was considered for each patient. This represents the first detailed analysis of PCs in CLL/SLL BMs. In our tertiary center, PCs were seen frequently, in approximately three-fourths of cases. There were no statistical associations identified between PCs and cytogenetic, immunophenotypic, or other laboratory and morphologic findings.

Bone marrow metastasis in nonhematologic malignancies: Data from a cancer hospital

Background: Bone marrow metastasis by a nonhematologic malignancy signifies advanced stage of disease and confers a poor prognosis. The aim of this study was to analyze clinical presentation, hematological profile, biochemical profile, radiological presentation, and patterns of bone marrow involvement in patients with metastatic nonhematologic malignancies retrospectively. Materials and Methods: Ninety bone marrow procedures were done in cases of nonhematologic malignancies for suspected involvement or as a part of staging procedure. Results: Sixteen out of 90 patients showed metastasis by nonhematologic malignancies. The most common malignancy to metastasize was malignant small round cell tumor (Ewing's sarcoma and rhabdomyosarcoma) followed by carcinoma breast and prostate. The most common clinical presentation was backache, fever anorexia, and abdominal pain. The biochemical findings included raised serum calcium and lactate dehydrogenase. 62.5% had anemia and 37.5% had thrombocytopenia. Leukocytosis was seen in 37.5% of patients. Leukoerythroblastic picture was seen in 43.75% cases. Of the eleven cases where both bone marrow aspirate and biopsies were done, 10 cases showed malignant cells in both. Immunohistochemistry was conclusive in four cases. The combined procedure of aspiration and biopsy gives a higher yield and are essential in patients with suspected bone marrow metastasis in nonhematologic malignancies.

Bone marrow involvement in Hodgkin's lymphoma: Data from a cancer hospital

Objective: Bone marrow examination is essential for staging Hodgkin's Lymphoma (HL) at the time of diagnosis to determine the correct treatment and prognosis of the disease. The aim of this study was to analyze clinical presentation, hematological profile, biochemical profile, radiological presentation and patterns of bone marrow involvement in patients with Hodgkins lymphoma retrospectively. Materials and Methods: Bone marrow procedures were done in 49 cases of Hodgkins lymphoma a part of staging procedure. Results: 9 patients showed involvement of bone marrow by Hodgkins lymphoma. Clinically, 1 patient was staged as stage II (CSII), 2 patients as stage III (CSIII) and the remaining 6 as stage IV (CSIV) on the basis of extra nodal evidence of disease in liver, bone, lung or pleura on PET scan. The pattern of bone marrow infiltration was diffuse in 3 patients and focal in 6 patients. Length of the biopsy varied from 0.5 cm to 3.0 cm. Conclusion: BME should not be performed in all patients diagnosed with HL as a routine staging procedure. In an already known CS IA, IIA the incidence is very low and in CSIV it provides no additional therapeutic or prognostic information. However, patients with stage IIB, IIIB, IIIA and with any of the following: leucopenia, elevated LDH or ALP levels, splenomegaly should undergo biopsy of adequate length as additional prognostic information may be obtained. If it is suspicious of involvement, serial sections and contralateral biopsies should be examined so that even a single atypical cell or focus is not missed.

Magnetic resonance imaging pattern of bone marrow involvement as a new predictive parameter of disease progression in newly diagnosed patients with multiple myeloma eligible for autologous stem cell transplantation

We investigated the prognostic value of the magnetic resonance imaging (MRI) pattern of bone marrow involvement in patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). 126 patients with untreated MM indicated for ASCT underwent spine MRI and cytogenetic analysis at diagnosis. All patients received ASCT after induction therapy of VAD (vincristine, doxorubicin, dexamethasone; n=55) or a thalidomide-based regimen (TCD; n=71). Thalidomide maintenance therapy was performed in 68 patients. The MRI pattern was normal in 27, focal in 47, and diffuse/variegated in 52 patients. Patients with the diffuse/variegated pattern showed significantly higher stage (P=0·038), higher β-2 microglobulin level (P=0·001) and severe anaemia (P=0·015). However, the cytogenetics were not different among the MRI patterns (P=0·890). Progression-free survival (PFS) was lower in the diffuse/variegated pattern (P=0·002) than other patterns, but not overall survival (OS) (P=0·058). Thalidomide maintenance therapy was correlated only with PFS (P= 0·001). High-risk cytogenetics were associated with both poorer PFS (P<0·001) and OS (P=0·003). In a multivariate analysis, the diffuse/variegated MRI pattern was an independent predictor of disease progression (Hazard Ratio, 1·922; 95% confidence interval, 1·185-3·118; P=0·008). The diffuse/variegated MRI pattern is a novel prognostic factor for disease progression in MM patients eligible for ASCT.

Clinicopathologic features and differential diagnosis of splenic B-cell marginal zone lymphoma involving bone marrow

To study the clinicopathologic features and differential diagnosis of splenic B-cell marginal zone lymphoma (SMZL) involving bone marrow. The clinical and pathologic features of 22 patients with SMZL were retrospectively studied. Immunophenotypic analysis was carried out by flow cytometry and immunohistochemistry. Immunoglobulin heavy chain rearrangement study was performed using polymerase chain reaction-based method. Villous lymphocytes were found in peripheral blood smears of 11/18 of the patients. In bone marrow aspirates, lymphocytosis (> 20%) was demonstrated in 15 cases (15/18) and villous lymphocytes in 6 cases (6/18). Flow cytometry showed CD19(+) CD20(+) FMC7(+) CD22(+) CD10(-) CD2(-) CD3(-) CD7(-) in 18 cases. Bone marrow biopsies of all the 22 patients revealed various degrees and patterns of neoplastic infiltration, as follows: mild (4 cases, 18.2%), moderate (11 cases, 50.0%) or severe (7 cases, 31.8%); intrasinusoidal (16 cases, 72.7%), interstitial (14 cases, 63.6%), nodular (11 cases, 50.0%) or diffuse (1 case, 4.5%). Reactive germinal center formation (CD23(+) bcl-2(-)) was found in 2 cases (91.0%). Immunohistochemical study showed the following results: CD20(+) PAX5(+) CD3(-) CD5(-) CD10(-) cyclin D1(-) CD23(-) CD43(-) Annexin A1(-) CD11C(-) CD25(-) in all the 22 cases, CD38(+) in 2 cases (9.1%) and CD138(+) in 2 cases (9.1%). Different and overlapping patterns of bone marrow involvement are observed in SMZL. As the histologic and immunophenotypic features are not specific to SMZL, distinction from other types of mature B-cell lymphomas is necessary.

High C-Terminal Cross-Linking Telopeptide of Collagen Type-I (CTX) Predicts for Poor Overall Survival in Patients with Multiple Myeloma Who Receive Frontline Therapy with Immunomodulatory Drugs (IMiDs) but Not with Bortezomib-Based Regimens

Abstract 935Lytic bone disease is a frequent complication of multiple myeloma (MM). Biochemical markers of bone metabolism provide information on bone dynamics and reflect activity in the bones. Several studies show that different bone markers are altered in myeloma patients, reflect the extent of bone disease and correlate with survival in the conventional chemotherapy era. Nevertheless, there is almost no information about their impact on the survival of myeloma patients who are treated upfront with novel agents.To address this issue we studied 122 consecutive, unselected, newly diagnosed patients with symptomatic MM (66M/56F, median age 71 years, range 36–88 years) who were diagnosed and treated in a single center (University of Athens, Greece). All patients received upfront novel agents: 75 patients IMiDs-based and 47 patients bortezomib-based regimens. The following bone remodeling markers were evaluated in the patients’ serum before the administration of any kind of therapy: i) osteoclast regulators: sRANKL and osteoprotegerin (OPG); ii) osteoblast inhibitor dickkopf-1 (Dkk-1); iii) bone resorption markers: CTX and TRACP-5b; and iv) bone formation markers: bone-specific alkaline phosphatase (bALP) and osteocalcin. The above molecules were also measured in 36 gender- and age-matched, healthy controls. Evidence of bone involvement was documented using plain radiographs and MRI of the spine in all patients.Twenty-five (20%) patients had ISS-I disease, while 46 (37%) patients had ISS-II and 51 (41%) stage ISS-III disease. Fifty-eight (47%) patients had Hb<10 g/dl and 24 (19%) patients had serum creatinine >2 mg/dl. The presence of lytic bone disease was documented in 76% of the patients. MRI evaluation of the spine revealed that 41% of the patients had focal, 38% diffuse, 19% normal, and 2% a variegated pattern of marrow involvement. At diagnosis, MM patients had increased serum concentrations of sRANKL (mean±SD: 0.4±0.5 pmol/L vs. 0.1±0.2 pmol/L; p<0.001), OPG (6.4±3.3 pmol/L vs. 4.2±1.7 pmol/L; p<0.001), CTX (0.90±0.97 ng/ml vs. 0.3±0.2 ng/ml; p<0.001),TRACP-5b (2.7±2 U/L vs. 1.6±0.7 U/L; p<0.001), Dkk-1 (59.4±38.7 ng/ml vs. 32.8±13 ng/ml; p<0.001) and sRANKL/OPG ratio (0.08±0.13 vs. 0.04±0.05; p=0.003) and decreased levels of bALP (21.6±15.1 U/L vs. 29.4±7.8 U/L; p=0.003) compared to controls, while their levels correlated with the extend of bone disease. Patients with diffuse pattern had higher CTX concentrations compared to all other others (0.95±1.2 ng/ml vs. 0.6±0.51 ng/ml; p=0.04). The median survival of all patients was 59 months. In the univariate analysis, among the studied bone markers, only CTX, as a continuous variable, was predictive of survival (HR: 1.292, p=0.024). Patients with low CTX concentrations (<0.28 ng/ml; lower quartile; N=29) had superior survival compared to patients with higher CTX concentrations (not reached vs. 54 months respectively; p=0.034). This was more profound in patients treated with IMiDs-based regimens: the median survival of those with low CTX levels (<0.28 ng/ml) has not been reached yet vs. 39 months of all others (p=0.02; Figure). There was no difference regarding the effect of CTX on survival between patients who received upfront thalidomide- or lenalidomide-based regimens. On the contrary, in patients who were treated with bortezomib-based schemes, high CTX could not define a poor prognosis group of patients. In patients with normal or focal MRI pattern of bone marrow involvement, low CTX concentrations also correlated with superior survival compared to all other patients (not reached vs. 54 months respectively; p=0.04). Serum LDH (as dichotomous variable >225 U/L; p=0.011, and as continuous variable; p=0.019), ISS stage (p=0.02) and anemia (Hb<10 g/dl; p=0.01) were also associated with survival in the univariate analysis. The presence of osteolytic disease at diagnosis had no impact on survival. In the multivariate analysis only ISS (p=0.02) and LDH (>225 U/L; p=0.038) were predictive for survival.Our study suggests that in the era of novel agents, only CTX, among 7 serum bone remodeling markers, correlated with survival. In particular, high CTX levels can distinguish a subset of patients who receive frontline IMiDs-based therapies and who have poor prognosis. This was not observed with bortezomib-based therapies, possibly due to the beneficial effect of bortezomib on bone metabolism. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: A single center experience on 228 patients

Magnetic Resonance Imaging (MRI) and specific cytogenetic abnormalities offer important prognostic information for myeloma patients. However, limited data are available about the association between cytogenetic abnormalities and MRI patterns of marrow infiltration. To address this issue, we analyzed 228 consecutive newly diagnosed, symptomatic patients who were diagnosed and treated in a single center. On bone marrow MR images, 95 (41%) patients had diffuse, 94 (41%) had focal, 35 (15%) were normal, and 4 (1.7%) patients had variegated pattern of marrow infiltration. High risk cytogenetics were more commonly observed with diffuse MRI pattern (50% vs. 31% in focal and normal patterns). Patients with diffuse MRI pattern had poorer survival compared to others and responded better to novel agent-based therapies than to conventional chemotherapy (objective response: 88% vs. 46%, P < 0.001). There was a significant improvement of patients' survival with a diffuse MRI pattern when treated upfront with novel agents compared to conventional chemotherapy (47 vs. 24 months; P < 0.001). Diffuse MRI pattern along with ISS-3 and high risk cytogenetics could identify a very high risk group of patients with extremely poor median survival (21 months) and an only 35% probability of 3-year OS. Our study shows that symptomatic myeloma patients with a diffuse MRI pattern at diagnosis very often show high risk cytogenetic abnormalities and are benefiting from upfront novel agent-based therapies. Diffuse MRI pattern in combination with high risk cytogenetics and ISS-3 can identify a subset of myeloma patients with very poor prognosis who may need innovative treatment strategies and possibly more aggressive therapies.