scholarly journals An Unsuspected Finding of t(9;22): A Rare Case of Philadelphia Chromosome-Positive B-Lymphoblastic Lymphoma

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Prajwal Boddu ◽  
C. Cameron Yin ◽  
Rashmi Kanagal-Shamanna ◽  
Guillin Tang ◽  
Beenu Thakral ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kinase Inhibitors ◽  
Bone Marrow Involvement ◽  
Philadelphia Chromosome ◽  
Lymphoblastic Lymphoma ◽  
Accurate Diagnosis ◽  
Biopsy Specimens ◽  
B Lymphoblastic Lymphoma ◽  
Prophylactic Chemotherapy

While rare, cases of isolated extramedullary disease of B-cell Lymphoblastic Lymphoma (B-LBL) without morphologic bone marrow involvement have been described. In this report, we illustrate the case of an elderly gentleman who presented with isolated testicular and vertebral LBL involvement but had no morphologic bone marrow involvement. The initial plan of treatment was to treat along the lines of Philadelphia negative B-ALL/LBL. During this time, fluorescence in situ hybridization (FISH) and PCR testing for BCR-ABL1 rearrangements were being performed on the marrow specimens as a part of routine diagnostic workup. While the FISH returned negative, PCR testing unexpectedly detected BCR-ABL1 fusion transcripts at a low level of 0.48%. Given their presence, we performed FISH for BCR/ABL1 rearrangement in both testicular and L5 vertebral specimens which were 80–90% positive. He subsequently received rituximab, hyper-CVAD, and dasatinib, along with prophylactic intrathecal prophylactic chemotherapy. The patient achieved a prolonged remission but eventually relapsed, 4 years later. Had it not been for this fortuitous discovery, the patient would not have been treated with tyrosine kinase inhibitors. We emphasize that FISH and PCR testing for BCR-ABL1 rearrangement are integral to arriving at an accurate diagnosis and should be routinely tested on B-LBL biopsy specimens.

Monitoring chronic myeloid leukemia (CML) response to tyrosine kinase inhibitors (TKI) and homoharringtonine (HHT) using peripheral blood (PB) fluorescence in situ hybridization (FISH) and quantitative RT-PCR (Q-PCR): Are bone marrow biopsies still needed?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7064-7064
Author(s):  
H. J. Khoury ◽  
L. Lima ◽  
D. Saxe ◽  
K. P. Mann ◽  
M. Arellano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kinase Inhibitors ◽  
Chromosomal Abnormalities ◽  
Philadelphia Chromosome ◽  
Disease Treatment ◽  
Bone Marrow Biopsies ◽  
Time Points ◽  
Additional Chromosomal Abnormalities ◽  
Reliable Methods

7064 Background: The purpose of this study is to compare simultaneously obtained PB and bone marrow (BM) BCR-ABL FISH and Q-PCR to monitor response to TKI and HHT in CML. Methods: Between January 2005 and December 2008, 52 patients (pts) with chronic (n = 37, 80%), accelerated (n = 6, 7%), and blast phase (n = 9, 14%) CML had 112 simultaneous PB and BM FISH and Q-PCR before and/or after start of imatinib (IM, n = 27), dasatinib (n = 9), nilotinib (n = 1), bosutinib (n = 13), or HHT (n = 2) for newly diagnosed (n = 27), IM resistant (n = 20), or IM intolerant (n = 5) CML. 13 (26%) had chromosomal abnormalities in addition to the Philadelphia chromosome, and 10 (20%) had a detectable BCR-ABL mutation including the T315I in 2 pts. Results: 24 (46%) had simultaneous PB and BM FISH and/or Q-PCR measurements obtained at 1 time point, 9 (17%) at 2; 9 (17%) at 3; 10 (20%) at > 4 time points before and/or post-initiation of TKI or HHT. Excellent concordance was observed between PB and BM at all time points for both FISH (r = 0.96; p = 0.0003) and Q-PCR (r = 0.88; p= 0.0015). Correlation was not affected by the presence of additional chromosomal abnormalities, phase of the disease, treatment (TKI or HHT), or the number of prior therapies. Conclusions: FISH and Q-PCR are reliable methods to monitor CML response to TKI and HHT in patients with CML and may render the need for BM biopsy monitoring obsolete. No significant financial relationships to disclose.

Leptomeningeal Precursor B-Cell Lymphoblastic Lymphoma in a Child With Minimal Bone Marrow Involvement

2004 ◽  
Vol 26 (7) ◽  
pp. 469-472 ◽  
Author(s):  
Oussama Abla ◽  
Ahmed Naqvi ◽  
Charles Ye ◽  
Rakesh Bhattacharjee ◽  
Mary Shago ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Bone Marrow Involvement ◽  
Lymphoblastic Lymphoma

High-Dose Methotrexate and Early Intensification of Therapy Do Not Improve 3 Year EFS in Children and Adolescents with Disseminated Lymphoblastic Lymphoma. Results of the Randomized Arms of COG A5971

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3610-3610 ◽  
Author(s):  
Minnie Abromowitch ◽  
Amanda Termuhlen ◽  
Myron Chang ◽  
Sherrie L. Perkins ◽  
Thomas Gross ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Involvement ◽  
Disease Free Survival ◽  
Lymphoblastic Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cns Disease ◽  
Dose Methotrexate ◽  
Significant Difference

Abstract The treatment of pediatric lymphoblastic lymphoma (LL) has developed in parallel with treatment strategies for childhood acute lymphoblastic leukemia using a BFM backbone. The excellent results of the NHL/BFM 90 trial prompted us to design this randomized factorial study to determine whether a regimen without high dose methotrexate (HDMTX) the CCG BFM will result in the same outcome as NHL/BFM-90 and whether intensification with anthracycline and cyclophosphamide would further improve disease free survival. From June 2000 to October 2005, 257 patients with Murphy’s Stage III and IV (excluding CNS disease) LL were randomized to one of the four regimens. All regimens used the BFM/NHL95 backbone. The CCG BFM regimen had intrathecal (IT) methotrexate throughout interim maintenance and maintenance without IV methotrexate. The NHL BFM utilized I.V. Methotrexate 5 Gms/m2 and intrathecal MTX every 2 weeks for four doses during interim maintenance without further intrathecal MTX during maintenance. One of each backbone regimens was further intensified with anthracycline and cyclophosphamide early in induction and delayed intensification. The median age was 10.3 years, 195 (76%) were males; 43 (17%) had >5% bone marrow involvement. Twelve patients with CNS disease were not randomized and received intensification and HD HDMTX with delayed CNS radiation (data not reported here). Major toxicities have been related to bone marrow suppression with 4 toxic deaths, 3 due to sepsis and 1 from cerebral hemorrhage. The frequency of grade III/IV neutropenia (alone, with fever or with infection), anemia, and thrombocytopenia were higher in the intensified arms during induction. Three of the four toxic deaths occurred on the intensified arms. The three years EFS of the HDMTX vs. none is 84.5% ± .3.5% vs. 82.7± 3.8 (ρ= 0.93) and the intensification vs. none is 83.4% ±3.7 vs 83.0% ± 3.6 (ρ= 0.66). Therefore, there was no significant difference between treatment arms. These results suggest that neither HDMTX nor early intensification improves EFS in LL. Future direction should focus on identifying biological factors early in therapy so alternative therapies may be investigated.

Evidence for Increased Bone Marrow Lymphoplasmocytoid Cells and SDF1 Secretion in imatinib Treated CML. Relationship with Clinical/hemathological Response

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4256-4256
Author(s):  
Ivana Pierri ◽  
Silvia Catellani ◽  
Francesca Olcese ◽  
Raffaella Grasso ◽  
Nicoletta Colombo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Lymphocytes ◽  
Kinase Inhibitors ◽  
Myelogenous Leukemia ◽  
Imatinib Treatment ◽  
First Line ◽  
Polymerase Chain ◽  
Chemotactic Effect

Abstract Tyrosine kinase inhibitors, such as imatinib mesylate (Gleevec, Novartis, formerly known as STI571) are confirmed to be the first line treatment of Chronic Myelogenous Leukemia (CML) and of a rare form of gastroenteric stromal cancer. It has been reported that in the latter case, the response to the drug in vivo is mainly due to immunocompetent cells, able to produce cytokines with antineoplastic activity. In this study, peripheral blood and bone marrow of 20 CML patients were studied, prior and during treatment with imatinib, to assess morphologic, phenotypic, cytogenetic and biomolecular patterns. Plasma from BM and PB was also tested to evaluate (by ELISPOT and real time polymerase chain reaction) cytokines able to induce B lymphocytes differentiation, and/or proliferation, such as interleukin (IL)-4, IL-6 (ligand for CD126), IL-3, IL-10 or IL-21 together with chemokines MCP-1, SDF-1, IP-10 and IL-8. In 14 out of 20 CML patients a significant increase in the percentage of BM lymphoplasmocytoid cells was observed on imatinib treatment with >10% (range 8–12%) of CD20+CD126+cells. Among this population, two third of cells coexpressed IgM and one third was IgD+, moreover a lower fraction of IgM+CD126+CD20− (3–4%) or IgD+CD126+CD20− (2–3%) cells was found too. In all these patients SDF1 increased in the BM plasma after imatinib (from 10–80pg/ml to 150–450pg/ml) and its receptor CXCR4 was up-regulated on CD20+CD126+cells. In 4 patients the amount of IP-10 in BM plasma and the expression of its receptor CXCR3 were also increased. No significant modification in transcription and secretion of IL-3, IL-4, IL-6, IL-10, IL-21, IL-8 or MCP1 were observed. The lasting 6 patients had<5% of CD20 +CD126+ lymphocytes (range2–4%), 2/3 coexpressing IgM and 1/3 coexpressing IgD. Every patients with increased number of CD126+ B lymphocytes achieved hemathologic remission, 7 of them complete cytogenetic and biomolecular remission. On the other hand, among the patients with low or undetectable CD20+CD126+cells, 2 obtained only hemathological remission. In the 2 relapsed patients, BM CD20+CD126+ lymphocytes decreased from 11% and 8% to 7 and 5%, respectively, with undetectable IgM+ CD126+CD20− or IgD+ CD126+CD20− cells. The increased production of SDF-1, following imatinib administration, might increase BM lymphoplasmocitoid cells, thanks to the double proliferative/chemotactic effect of the cytokine on B cells, with redistribution and in situ differentiation of CD20+ CD126+ lymphocytes. These findings shed some light on the possibility that, even in CML, immunological events may play a role in disease control;moreover they could be useful in monitoring disease outcome.

Successful therapy of convoluted T-lymphoblastic lymphoma in the adult

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 92-98
Author(s):  
AM Levine ◽  
SJ Forman ◽  
PR Meyer ◽  
SC Koehler ◽  
H Liebman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Survival ◽  
Bone Marrow Involvement ◽  
Cranial Irradiation ◽  
Lymphoblastic Lymphoma ◽  
Intrathecal Methotrexate ◽  
Induction Phase ◽  
Relapse Free Survival ◽  
Free Survival ◽  
T Lymphoblastic Lymphoma

Fifteen adult patients with biopsy-proven convoluted T-lymphoblastic lymphoma were treated with an aggressive regimen, modified from the LSA2-L2 protocol used for childhood lymphoma. The treatment schema consisted of induction phase, including cyclophosphamide, vincristine, prednisone, adriamycin, and 2000 rads to mediastinum, as well as intrathecal methotrexate. Consolidation phase included cytosine arabinoside, 6-thioguanine, L-asparaginase, and CCNU, along with cranial irradiation and further intrathecal methotrexate. Maintenance consisted of cyclical chemotherapy and intrathecal methotrexate, continuing for a total of 3 yr. Median age in the group was 25 yr (range 16–73). There were 8 males and 7 females. At diagnosis, 9 patients had mediastinal involvement, and 9 had bone marrow involvement. Five of these demonstrated malignant cells in the peripheral blood. Complete clinical response was attained in 11 patients. Three patients achieved partial response. Four complete responders have relapsed, 1 in the central nervous system at 6 mo. and 1 in nodal sites at 3 mo, 1 in multiple sites at 24 mo. and 1 in bone marrow at 42 mo while off all chemotherapy for 6 mos. At this time, median survival of all patients is 28.3 mo. and median relapse-free survival is 21 mo. The median survival for complete responders in excess of 71 mo. while the median relapse-free survival for this group is 41 mo.

scholarly journals Precursor B Lymphoblastic Lymphoma Involving the Stomach

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Masaya Iwamuro ◽  
Yoshinari Kawai ◽  
Yasuhide Yamawaki ◽  
Katsuyoshi Takata ◽  
Kazuhide Yamamoto
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lineage ◽  
Lymphoblastic Lymphoma ◽  
High Grade ◽  
Gastrointestinal Lesions ◽  
B Lymphoblastic Lymphoma

Precursor B lymphoblastic lymphoma is a high-grade neoplasm arising from precursor lymphocytes of B-cell lineage. Extranodal sites such as the skin and bone are often involved, but gastrointestinal lesions of this disease are rarely encountered. Due to the infrequency, macroscopic forms of the gastrointestinal lesions have not been fully described. In this report, we present a case of precursor B lymphoblastic lymphoma involving the stomach, pancreas, bone, and bone marrow. Esophagogastroduodenoscopy showed multiple flat elevated lesions with irregular mucosa in the stomach.

scholarly journals Essential Thrombocythemia: Current Molecular and Therapeutic Insights

2015 ◽  
Vol 5 (1) ◽  
pp. 5-10
Author(s):  
Fatin M. Al-Sayes ◽  
Kalamegam Gauthaman
Keyword(s):  
Essential Thrombocythemia ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Myeloproliferative Disorders ◽  
Integrated Approach ◽  
Accurate Diagnosis ◽  
World Health ◽  
Systematic Analysis ◽  
Hematopoietic Stem ◽  
Health Organization

Essential thrombocythemia is one of the Philadelphia chromosome negative, clonal myeloproliferative disorders involving the hematopoietic stem cells and is characterized by elevated platelet counts and attendant thromboembolic phenomenon. A point mutation in the Janus-Activated Kinase 2 gene (JAK2V617F) accounts for nearly 50% of Essential thrombocythemia patients while about 10% have mutations in the thrombopoetin receptor (MPL) gene (MPLW515L/K). Several other genes are implicated, clearly indicating the existence of drivers both common and uncommon in the causation of Essential thrombocythemia. Genotyping for mutations will therefore be a useful diagnostic tool for detection of Janus-Activated Kinase 2 negative, MPL negative, Essential thrombocythemia patients. An integrated approach of systematic analysis leading to accurate diagnosis will enable risk stratification and institution of therapy following the World Health Organization guidelines. In addition to Janus-Activated Kinase inhibitors, a combination of agents that has anti-inflammatory properties could help prevention and/or reversal of fibrosis.

Clinical features, molecular aberrations, treatments, and outcomes in histiocytic sarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7020-7020
Author(s):  
Gordon Ruan ◽  
Gaurav Goyal ◽  
Nabila Nora Bennani ◽  
Mithun Vinod Shah ◽  
Karen Rech ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kinase Inhibitors ◽  
Proportional Hazards ◽  
Bone Marrow Involvement ◽  
Cox Proportional Hazards ◽  
Histiocytic Sarcoma ◽  
Braf V600e ◽  
Variable Response ◽  
Kaplan Meier ◽  
Multifocal Disease

7020 Background: Histiocytic sarcoma (HS) is a rare and aggressive malignancy of the monocyte/macrophage lineage. There is a paucity of data on treatments and outcomes in HS. Methods: This is a retrospective study of patients with histologically confirmed diagnosis of HS from 2000-2018. Kaplan-Meier and log-rank tests were used to perform overall survival (OS) analyses. Hazard ratios (HR) with confidence intervals (CI) were calculated using Cox-proportional hazards. Results: There were 27 patients in the study (median age 59; range 3-83) and 63% were males. Nine had unifocal involvement and 18 had multifocal disease. Common sites involved were lymph node (50%), soft tissue (40%), bone (36%), and bone marrow (22%). Two of 8 patients had the BRAF-V600E mutation. Next-generation sequencing was performed on 8 patients and showed ≥1 oncogenic alterations (DNMT3A, FLT4, KRAS, NRAS, NUP98, PTCH1, PTPN11, TP53, TSC1, PDGFR, or BRAF genes) as well as a CLIP2-BRAF fusion. The median OS for the cohort was 12 months. Factors associated with worse OS included multifocal disease (OS 10 vs. 125 months, p = 0.03; HR 5.0, CI 1.1-21.8) and marrow involvement (OS 3 vs. 43 months, p = 0.003; HR 8.9, CI 1.7-45.0). Twelve (44%) had surgery with median OS of 42 months (range 1-125). Fifteen had chemotherapy with median OS of 12 months (range 2-67; Table). Conclusions: HS is an aggressive neoplasm, with multifocal disease and bone marrow involvement portending worse outcomes. Most patients have somatic oncogenic alterations involving the MAPK-ERK pathway and other genes. Chemotherapeutic regimens have variable response rates but are not durable. More studies on targeted kinase inhibitors in HS are needed to improve outcomes. [Table: see text]

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