Standard of Care of Patients with CML Treated in Community Based Oncology Group Practices in Rhineland-Palatinate (Germany)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2376-2376
Author(s):  
Rudolf Weide ◽  
Bernhard Rendenbach ◽  
Monika Grundheber ◽  
Oswald Burkhard ◽  
Joachim Behringer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Conflicts Of Interest ◽  
Clinical Care ◽  
Standard Of Care ◽  
Fish Analysis ◽  
Line Treatment ◽  
Oncology Group ◽  
Community Based ◽  
Group Practices

Abstract Introduction: Significant progress has been made in CML-therapy since the introduction of imatinib and other tyrosine kinase inhibitors (TKI) into clinical care. The aim of this study was to assess diagnosis, treatment and outcome of CML-patients who received their treatment in community based oncology practices in Rhineland-Palatinate and whether European LeukemiaNET-guidelines were followed. Methods: All Ph-/BCR-ABL-positive CML-patients who were treated between 12/2001-12/2015 in 9 oncology group practices were analyzed retrospectively concerning diagnosis, treatment and outcome according to European LeukemiaNET-guidelines. Data were collected from patient files into a central data base and analyzed statistically with SPSS. Results: 264 patients (pts) with a median age of 60 (18-90) were analyzed. 126 (48%) were female, 138 (52%) were male. At initial diagnosis bone marrow biopsy was performed in 213 pts (81%). Cytogenetics was applied in 204 pts (77%) (38% in blood, 56% in bone marrow). FISH-analysis was used in 155 pts (59%) (33% in blood, 36% in bone marrow). PCR-testing to detect a BCR-ABL1-rearrangement was applied in 200 pts (76%) (52% blood, 37% bone marrow). 258 pts (98%) were in chronic phase, 5 (2%) in accelerated phase and 1 (0.4%) in blast crisis at diagnosis. EUTOS score could be calculated in 131 pts (50%). 20% were high risk, 80% low risk. 252 pts (95%) received some form of TKI-therapy. Out of 416 TKI-therapies 308 (74%) were PCR-based monitored, 148 (36%) were monitored by cytogenetics. First line treatment was imatinib in 201 pts (80%), 51 pts (20%) received a second generation TKI. Second line treatment consisted of dasatinib in 59%, nilotinib in 32%, imatinib in 6% and bosutinib in 3%. Third line treatment was nilotinib in 56%, dasatinib in 35%, ponatinib in 6% and imatinib in 3%. 62 pts (23%) were treated within a study protocol. 13 pts (5%) received an allogeneic transplantation. Overall survival probability was 88% after 5 years and 72% after 10 years. Disease specific survival was 95% after 5 years and 86% after 10 years. Conclusion: The overwhelming majority of CML-patients treated in oncology group practices receive standard of care as suggested by European LeukemiaNET-guidelines. Overall survival in routine care is comparable to international studies. Disclosures No relevant conflicts of interest to declare.

High Grade Non-Hodgkin’s Lymphoma with Tandem t(14;18) and c-MYC Rearrangement Is a Pathological Lymphoma Entity with Aggressive Clinical Presentation and Very Poor Prognosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2045-2045
Author(s):  
Cyrille Touzeau ◽  
Pascaline Talmant ◽  
Anne Moreau ◽  
Richard Garand ◽  
Herve Avet-Loiseau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Hematopoietic Cell Transplantation ◽  
Clinical Presentation ◽  
Bone Marrow Involvement ◽  
Stage Iv ◽  
Prior History ◽  
Fish Analysis ◽  
Allogenic Bone ◽  
Over Expression

Abstract Translocation t(14;18)(q32;q21) is a hallmark of follicular lymphomas (FL) and reported in 10% to 40% of diffuse large B cell lymphomas (DLBCLs). It leads to Bcl-2 over expression, a protein that opposes to mitochondrial apoptotic pathways and chemotherapy-induced cell death. c-MYC (8q24) rearrangement is a hallmark of Burkitt’s lymphoma (BL) but observed in 7% to 15% of DLBCLs. c-MYC (8q24) induces over expression of c-MYC protein which promotes cell cycle and tumour proliferation. Among 70 DLBCL expected for c-MYC and t(14;18) translocation, we identified a series of 16 patients with DLBCL characterized by a tandem t(14;18) translocation and c-MYC rearrangement. Patients were 10 males, 6 females with a median age of 59 years old (36–73). At the time of diagnosis, all patients presented with poor features: B symptoms in 81%, ECOG PS > 2 in 81%, elevated LDH in 100% , stage IV in 100 % with at least one extra nodal localisation (bone marrow involvement in 87,5% and CNS involvement in 44%) and age-adjusted IPI = 3 in 81%. Lymphoma cells in blood smear was found in 50% of the cases. Three patients had a prior history of FL. All patients but one were treated with chemotherapy regiments: R-CHOP like (n=8) or Burkitt regiments (n=7). Five patients reached complete response, 7 partial response and 4 patients progressed. Five patients underwent ASCT (n=3) or allogenic bone marrow transplantation (n=2) upfront. However, disease response was dramatically short precluding planned hematopoietic-cell transplantation in most cases. Despite salvage chemotherapy, all patients progressed with a median time to progression from diagnosis of 4 months (1–10) and median overall survival of 5 months (1–16). Morphological and immunophenotypic findings were consistent with the diagnosis of DLBCL with a germinal-center (GC) profile(CD10 + and CD10−/BCl6+/Mum1−) in all cases. Combination of t(14;18) translocation and MYC rearrangement was identified by conventional cytogenetic and/or FISH analysis in all cases. Conventional cytogenetic found 3 patients with t(8;14), 3 patients with t(8;22) and one with t(2;8) translocation. We also identified a new MYC translocation variant that has never been reported in DLBCL before : t(8;9)(q24;p13) translocation in combination with t(14;18)(q32;q21) translocation. All cases assessed by cytogenetic analysis had a complex karyotype. FISH analysis for BCL6 was positive for only 3 patients. Our series shows that DLBCL with a tandem t(14;18) and c-MYC rearrangement is a particular sub-type of GC-DLBCL with aggressive initial clinical presentation and a disastrous overall survival. We conclude that patients with DLBCL with unusual aggressive clinical and biological presentation should be investigated for tandem translocation. These patients require innovative strategies and targeted therapies.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Three Novel AML Cases Harboring the Semi-Cryptic t(7;21)(p22;q22) Translocation Expressing RUNX1-USP42 Fusion Transcripts Associated with Diploidy/Tetraploidy and/or 5q Alterations: a Probably Underestimated Combination

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2708-2708
Author(s):  
Eric Jeandidier ◽  
Carine Gervais ◽  
Isabelle Radford-Weiss ◽  
Catherine Gangneux ◽  
Valerie Rimelen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Fusion Transcript ◽  
Fish Analysis ◽  
Chimeric Transcript ◽  
Rt Pcr ◽  
Balanced Translocation ◽  
Fusion Transcripts ◽  
Cryptic Translocation

Abstract Abstract 2708 RUNX1 is implicated in numerous chromosomal abnormalities acquired in acute myeloid leukemia (AML). The most frequent one, the t(8;21) is associated with a particular morphology together with a favorable prognosis. This is not the case for other 21q abnormalities, that are much less frequent and for which the prognosis is quite different. Moreover, beside point mutations, conventional cytogenetics failed to detect some of chromosomal alterations involving RUNX1. Recently 3 cases of the rare and semi-cryptic t(7;21)(p22;q22) translocation expressing the RUNX1-USP42 fusion transcripts have been reported, demonstrating the recurrence of this abnormality in AML. We describe here 3 additional cases with the same translocation and fusion transcripts, associated to 5q alterations leading to EGR1 and CSF1R heterozygous losses. In all our patients, the t(7;21)(p22.1;q22.3) was initially detected by the systematic FISH evaluation of the blastic populations using ETO-AML1 Dual Fusion probe. Patient#1 bone marrow karyotype was characterized by a tetraploid clone (89,XXYY) with loss of chromosomes 15, 17 and 18 in addition to the t(7;21), and a unbalanced translocation der(5)t(5;13)(q23;q?) between long arms of chromosomes 5 and 13, resulting in a heterozygous loss of EGR1 and CSF1R. Patient #2 blood and bone marrow karyotypes revealed a diploid clone with a del(5)(q31q33) associated with the t(7;21). The FISH analysis confirmed EGR1 and CSF1R deletions. In patient #3, the bone marrow karyotype showed diploid/tetraploïd clones, both harboring the t(7;21)(p22;q22), confirmed by FISH experiments (WCP7, AML1 probes). In addition, a der(5)t(1;5)(q3?2;q21-23) was identified within the tetraploïd clone, resulting in the loss of EGR1 and CSF1R, confirmed by FISH. In all three cases a RUNX1-USP42 fusion transcript was detected using RT-PCR, as well as the reciprocal transcript. Sequence analysis of RT-PCR products showed that the breakpoints occurred exactly in the same introns of USP42 and RUNX1 as in the previously described cases. For patient #1 and #3 a chimeric transcript was found formed of the RUNX1 exon 7 fused to the USP42 exon 3. In patient #2, a shorter chimeric transcript arised from the fusion of the RUNX1 exon 5 to the exon 3 of USP42. As already noticed in the previous reports, an alternative splicing of the RUNX1 exon 6 has been detected in these three cases. The description of these 3 novel t(7;21) confirm the recurrence of this balanced translocation in AML, and shows that this chromosomal abnormality is often associated with diploid/tetraploid clones and/or 5q alterations. Special attention should be paid in karyotype analysis of AML with diploid or tetraploid clones harboring 5q alterations. In such cases RUNX1 rearrangements should be explored using FISH analysis, and RUNX1-USP42 fusion transcript should be searched by RT-PCR in positive cases. Prospective and retrospective studies of AML have now to be settled in order to assess the incidence and clinical relevance of this cryptic translocation. Disclosures: No relevant conflicts of interest to declare.

Bone Marrow Failure with 13q Deletion: A Distinct Clinicopathological Entity with Immune Pathophysiology,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3420-3420
Author(s):  
Kohei Hosokawa ◽  
Takamasa Katagiri ◽  
Naomi Sugimori ◽  
Ken Ishiyama ◽  
Yumi Sasaki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Bone Marrow Failure ◽  
Survival Rates ◽  
Snp Array ◽  
Normal Karyotype ◽  
Genetic Alterations ◽  
Fish Analysis ◽  
Hematopoietic Stem ◽  
Who 2008

Abstract Abstract 3420 Background: Numerical karyotypic abnormalities such as −7/del(7q) and del(13q) are occasionally seen in patients with bone marrow (BM) failure who do not have typical signs of myelodysplasia. The WHO 2008 defined this subset of BM failure as MDS-U because of its likely association with a risk of evolving into leukemia, while the presence of isolated abnormalities including +8, del(20q), and -Y was not considered to be presumptive evidence of MDS. Previous studies showed that BM failure patients with del(13q) responded to immunosuppressive therapy (IST) and had a favorable prognosis (Ishiyama K et al, Br J Haematol; 117: 747. 2002; Sloand, JCO 2010). However, the clinical features of del(13q) BM failure remain unclear due to its low incidence as well as the frequently associated karyotypic abnormalities. Objectives/Methods: To characterize the clinicopathological features of patients with BM failure with del(13q), this study reviewed the clinical data of 1705 BM failure patients (733 with AA, 286 with MDS-RCUD, 149 with RCMD, 60 with MDS-U) whose blood was examined for the presence of glycosylphosphatidyl-inositol anchored protein (GPI-AP)-deficient granulocytes and erythrocytes from May 1999 through July 2010. Genomic DNA was isolated from the peripheral blood cells of 7 patients with 13q- and was subjected to SNP array-based genome-wide analysis for genetic alterations using GeneChip® 250K arrays to identify the gene locus that is commonly deleted as a result of 13q-. Results: The 13q- clone was found in 25 (1.5%) of the 1705 patients. All the 13q- patients were classified as MDS-U, due to the absence of significant dysplasia to fulfill the criteria for MDS defined by the WHO 2008 classification. BM was hypocellular in 17 patients and normocellular in 6. Seventeen patients had a clone with 13q- alone, while the remaining 8 patients had a clone with 13q- and other numerical abnormalities including –Y, +mar in 2, and −20, del(7q), +8, der(1;7) in 1. A significant increase in the percentage of GPI-AP- granulocytes was detected in 366 (50%) of 733 patients with AA and 115 (23%) of 495 patients with MDS. GPI-AP- cells were detected in all (100%) of the 17 patients with 13q- alone. On the other hand, the prevalence of increased GPI-AP− cells in patients with 13q- plus other abnormalities and in those with the normal karyotype was 38% (3/8) and 43% (405/937), respectively. Fifteen patients with 13q- alone were treated with IST (ATG + cyclosporine in 6 and cyclosporine ± anabolic steroid in 9) and all of them achieved either a PR or a CR, while in the patients with 13q- plus other abnormalities, the response rate to IST was 40%. A total of 106 patients with the normal karyotype were treated with ATG+CsA (48) or CsA±AS (58) and the response rates were 73% and 85%, respectively. None of the 17 13q- patients progressed to advanced MDS or AML during the follow-up period of 3 to 108 months (median: 52 months) while 2 of 8 patients with 13q- plus other abnormalities developed AML. The 5-year overall survival rates of the patients with 13q-, those with 13q- plus other abnormalities, and patients with a normal karyotype were 84%, 45%, and 91%, respectively. The percentage of 13q- clones increased in 5 patients, and decreased in 3 patients after successful IST. When GPI-AP- and GPI-AP+ granulocytes were subjected to a FISH analysis using a 13q probe (13q14.3), the 13q- clones were detected only in of GPI-AP+ granulocytes, suggesting that 13q- cells are derived from non-PIG-A mutant HSCs. SNP arrays identified 13q13.3 to 13q14.3 regions in all cases. Conclusions: MDS-U with 13q- is a benign BM failure syndrome characterized by a good response to IST and a markedly high prevalence of GPI-AP cells. Patients with this type of BM failure may be inappropriately treated with hypomethylating agents or hematopoietic stem cell transplantation from unrelated donors, which is associated with high therapy-related mortality. Therefore, del(13q) should be eliminated from the intermediate prognosis group defined by the IPSS, and BM failure with del(13q) should be managed as idiopathic AA. Disclosures: No relevant conflicts of interest to declare.

Multiple Copies of MLL Is The Most Commonly Detected Cytogenetic Abnormality In Newly Diagnosed Multiple Myeloma and May Modify Disease Risk

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1910-1910 ◽  
Author(s):  
Chrystal Landry ◽  
Dory Londono ◽  
Sean M. Devlin ◽  
Alex Lesokhin ◽  
Nikoletta Lendvai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Protein Translation ◽  
Response To Therapy ◽  
Cytogenetic Abnormality ◽  
Newly Diagnosed

Abstract Background Multiple myeloma (MM) is a heterogeneous condition with variable disease course, response to therapy, and survival outcome. Cytogenetics and fluorescent in-situ hybridization (FISH) have identified several recurrent chromosomal aberrations in MM and play important and independent roles in risk stratification (Munshi et al. Blood 2011). However, the pathogenesis of the disorder remains poorly understood. Next-generation sequencing has recently identified that MM involves mutations of genes with roles in protein translation, histone methylation, and blood coagulation (Chapman et al. Nature 2011). Based on the observation that extra copies of MLL, a histone methyltransferase known to regulate the homeotic transcription factor HOXA9 that is highly expressed in MM, is frequently detected in MM, we sought to define the incidence and prognostic significance of excess MLL in MM patients. Methods We identified 188 patients with newly diagnosed MM who had cytogenetics and/or FISH performed on initial, pre-treatment bone marrow specimens at Memorial Sloan-Kettering Cancer Center between January 2009 and December 2012. Standard karyotype and FISH were performed as previously described (Cigudosa et al. Blood 1998, Gerritsen et al. Blood 1992). Probes included LSI IgH/FGF3, LSI IgH/CCND1, LSI IgH/MAF, LSI MLL, LSI p53/cep17, LSI13q14.3/13q34, LSI ETV6, LSI CBFB, LSI 1p36/1q25, and LSI 5,9,15 from Abbott Molecular. Fisher's exact test evaluated the association between MLL and selected abnormalities. Kaplan-Meier methodology estimated overall survival from the date of BM evaluation, and survival was compared using a logrank test. Results In unselected bone marrow specimens, abnormalities were detected by karyotype in 17% (27/156) and FISH in 47% (87/186) of patients tested. Hyperdiploidy, which has been associated with longer survival, was identified in 23% (43/187) of patients, while the unfavorable risk abnormalities, including loss of p53, deletion 13q (by karyotype), translocation (4;14) and excess 1q were seen in 8% (15/179), 8% (12/156), 4% (7/176) and 16% (29/178) of patients, respectively. Translocation (11;14) was seen in 4 patients; translocation (14;16) was not identified in any patient. 28% (51/183) of patients had extra copies of MLL, which was the most frequent genetic abnormality identified. Unexpectedly, this abnormality was significantly associated with both favorable (hyperdiploidy, P = <0.001) and unfavorable (deletion 13q, P = 0.043; excess 1q P = 0.001) risk genetics. While having excess MLL had no impact on the overall survival of standard-risk patients, defined as neither hyperdiploid nor with unfavorable genetics (N = 100), patients with poor-risk genetics (N = 46) and extra copies of MLL had a trend toward better survival, P = 0.06 (Figure 1). Conclusions Karyotype and FISH studies identified excess MLL as the most frequent cytogenetic abnormality in a large cohort of newly diagnosed MM patients. In patients with MM and unfavorable cytogenetics, the presence of excess MLL may ameliorate some of the adverse impact of associated with these abnormalities. Understanding the functional significance of excess MLL, perhaps as it relates to frequently dysregulated HOXA9 in MM, may provide insight into disease pathogenesis and/or identify drugable targets. Disclosures: No relevant conflicts of interest to declare.

A Translocation (9;22)(p24;q11.2) In a Patient With CML

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5184-5184
Author(s):  
Daniele Costa Abreu ◽  
Ana Paula Castilho, Bachelor ◽  
Vivian Dionísio Niewiadonski, Bachelor ◽  
Mauricio Drummond ◽  
Nelson Gaburo
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Medical Information ◽  
Conflicts Of Interest ◽  
Philadelphia Chromosome ◽  
Chromosome Analysis ◽  
Chromosome 9 ◽  
Fish Analysis ◽  
Ph Chromosome

Abstract Introduction In January 2013 was received in our lab service a bone marrow sample for cytogenetic analysis. The 61 years old female patient presents an elevated white blood cell count (118,000 x10³/mm³) and clinical diagnosis as Chronic Myeloid Leukemia (CML). According the medical information the treatment began with hydroxyurea 3g daily and allopurinol 300mg daily. Methods We proceeded with cytogenetic examination of the patient’s bone marrow aspirate by conventional G-banding analysis performed on unstimulated short-term cultures (24 hrs). FISH for BCR/ABL translocation was tested using a dual fusion dual color probe. Because of the sample stability we were unable to performed RT-PCR test. Results Chromosome analysis showed the translocation (9;22)(p24;q11.2) as a sole abnormality in 100% (20/20) of analyzed metaphases. Chronic myeloid leukemia presents as a specific chromosomal abnormality the Philadelphia chromosome, t(9;22)(q34;q11) which is different from the results obtained where the region of translocation of chromosome 9 was p24 instead of the classic q34. This result suggests it is BCR/JACK2 translocation. The FISH analysis showed the presence of a complex Ph chromosome: ABL con BCRx1 (one fusion) and BCRx2;ABLx2. Conclusion The patient took imatinib without answer. She is still in clinical monitoring with persistent hyperleucocytosis and the treatment is following with hydroxyurea 500mg daily and Interferon 5000 UI three times a week. Further molecular and cytogenetic tests will be performed in a second sample to contribute with evaluation of disease progression and monitoring treatment response. Disclosures: No relevant conflicts of interest to declare.

An Analysis of CNS2 Patients with AML: Do They Require Additional Intrathecal Therapy? a Report from Children’s Oncology Group Protocols AAML0531 and 03P1 and St Jude Children’s Research Hospital Protocol AML02

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 277-277 ◽  
Author(s):  
Donna Johnston ◽  
Jeffrey E Rubnitz ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Richard Aplenc ◽  
...  
Keyword(s):  
Overall Survival ◽  
Conflicts Of Interest ◽  
White Blood Cells ◽  
Study Entry ◽  
Intrathecal Therapy ◽  
Oncology Group ◽  
Research Hospital ◽  
Cns Disease ◽  
Cns Relapse ◽  
The Impact

Abstract Introduction: Pediatric patients with acute myeloid leukemia (AML) require central nervous system (CNS) directed chemotherapy to minimize CNS relapse. Patients with AML who have CNS disease at diagnosis, defined as >5 white blood cells (WBC) with positive blast in cytospin, require more intensive CNS directed therapy to clear CNS disease and prevent CNS relapse. Those with <5 WBC but with a positive cytospin are designated as CNS2 disease. Those without any blast (negative cytospin) are designated as CNS1. The need for extra CNS therapy for CNS2 patients varies among treatment protocols, and consensus has not been reached as to the best CNS directed therapy for these patients. We studied the impact of intensive vs. standard management of CNS2 patients by comparing patients treated on the two most recent Children’s Oncology Group (COG) trials to those treated on the St Jude Children’s Research Hospital AML02 trial, where COG trials managed those with CNS2 disease more intensively, similar to CNS3, and AML02 treated such patients similar to CNS1. Both trials used a similar MRC-based chemotherapy backbone. This backbone gave intrathecal (IT) cytarabine at the beginning of each cycle of therapy except Capizzi II therapy, and on the AML02 protocol most patients received IT triple therapy. On both backbones, patients with CNS3 disease, and those on COG trials with CNS2 disease, received twice weekly IT cytarabine until the CSF was clear of blasts plus 2 additional treatments with a minimum of 4 IT treatments given. Thus, this analysis is the first comparison of outcome of CNS2 patients examining the variable of additional CNS directed therapy. Methods: Disease characteristics and clinical outcome for children who were CNS2 treated with intensive or standard intrathecal chemotherapy were compared across COG and SJCRH studies and compared to those who were CNS1 or CNS3. Results: Among the 1361 eligible patients enrolled on AAML03P1 and AAML0531 with available data for CNS status, 247 had CNS2 status. Of the 200 eligible patients enrolled on AML02, 47 patients had CNS2 status. On all protocols, patients with CNS2 status had a significantly higher incidence of Inv(16) compared to CNS1 patients (p<0.001 for both protocols). As well, patients with CNS2 status had a higher incidence of M4 FAB classification compared to CNS1 patients (p<0.001 for COG protocols and p=0.002 for AML02). On both protocols, patients who were CNS2 had similar incidence of Inv(16) compared to patients who were CNS3. In contrast, on the COG protocols the incidence of M4 FAB was similar among CNS2 and CNS3 patients, while on the AML02 protocol the incidence of M4 FAB was significantly higher in CNS2 compared to CNS3. The event free survival (EFS) for patients treated on COG protocols showed significant differences according to CNS status, with CNS1 patients having superior EFS compared to CNS2 and CNS3 patients (p=0.005), while on AML02, the EFS for CNS2 patients was significantly higher than CNS3 patients (p=0.04) and higher, but not significantly, than CNS1 patients (p=0.06). The overall survival (OS) for CNS2 patients treated on COG protocols was not significantly different from that of CNS1 and CNS3 patients (p=0.32), while on AML02, the OS was significantly higher for CNS2 patients compared to CNS1 (p=0.05) and CNS3 patients (p=0.02)(Figures 1 and 2). However, for the AML02 protocol, the Cox analysis showed that CNS status was not independently associated with EFS, OS, or cumulative incidence of relapse On the COG protocols there were 101 patients with relapse involving CNS, of which 34 were CNS1, 32 CNS2 and 34 CNS3 with a 5 year CNS refractory/relapse rate of 4%, 13% and 28% respectively (p<0.001). One patient with CNS relapse was unknown for CNS group. Of the 101 patients who relapsed involving CNS: 34% were CNS1, 32% were CNS2, and 34% were CNS3. Conclusions: Patients with AML who have <5 white cells with blasts present in the cerebrospinal fluid at diagnosis may not require extra IT therapy but may be able to be treated in the same fashion as patients with no blasts in the CSF at diagnosis. Additional analyses will assist in determining which, if any, CNS2 patients require extra IT therapy. Figure 1 Figure 1. – Overall Survival From Study Entry for Patients on COG AAML03P1 and AAML0531 Figure 2 Figure 2. – Overall Survival from Study Entry for Patients on SJCRH AML02 Disclosures No relevant conflicts of interest to declare.

The Frequency of Genetic Anomalies According to Clonal Plasma Cells' Phenotype in Patients with Newly Diagnosed (ND) Multiple Myeloma (MM)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5316-5316
Author(s):  
Andrei Garifullin ◽  
Irina Martynkevich ◽  
Sergei Voloshin ◽  
Alexei Kuvshinov ◽  
Ludmila Martynenko ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
Risk Groups ◽  
Fish Analysis ◽  
Newly Diagnosed ◽  
Definition Of ◽  
Standard Risk

Abstract Background. Genetic anomalies (GA) are primary link of pathogenesis in MM. GA lead to formation of clonal plasma cells, which has different phenotype. Aim. To estimate the incidence of GA and their correlation with clonal plasma cells' phenotype in patients with ND MM. Methods. We analysed 22 patients with ND MM (median age 57 years, range 38-80; male/female - 1:1.75). Cytogenetic analysis was performed on bone marrow samples using standard GTG-method. Metaphase FISH analysis was performed according to the manufacturer's protocol using DNA probes: LSI 13(RB1)13q14, IGH/CCND1, IGH/FGFR3, LSI TP53 (17q13.1). 8-color immunophenotypic by flow cytometry using antibody to CD45, CD38, CD138, CD56, CD19, CD20, CD27 and CD117 antigenes. Results. Translocation t(11;14) was detected in 3/14 (21.4%) patients, del(13q) - 2/14 (14.3%), t(11;14) - 3/14 (21.4%), hypodyploidy - 1/20 (5%), del(17р) - 0% patients. Clonal plasma cells' phenotype CD38+CD138+CD45- was detected in 100%. Expression CD56+ was revealed in 11/22 (50%) patients, CD19+ in 9/22 (40.9%), CD117+ in 5/22 (22.7%), CD20+ in 1/22 (4.5%), CD27+ in 1/22 (4.5%). The frequency of GA didn't depend on clonal plasma cells' phenotype and was 27.3%(3/11) in CD56+ phenotype, 23.8%(5/21) - CD20-, 23.8%(5/21) - CD27-, 23.5%(4/17) - CD117-, 23%(3/13) - CD19-, 22.2%(2/9) - CD19+, 20%(1/5) - CD117+, 18.2%(2/11) - CD56-, 0%(0/1) - CD20+, 0%(0/1) - in CD27+ phenotype. Patients of standard risk group according to mSMART 2.0 with GA had CD19-negative plasma cells' phenotype vs. CD19-positive phenotype in patients of intermediate and high-risk groups (p<0.05). 3-years overall survival in standard risk group with CD19- phenotype was 92,3%, CD19+ - 77,7% (p>0.05). Conclusion . Identification of GA, which has adverse forecast, correlates with CD19+ plasma cells phenotype. The combined definition of plasma cells phenotype and GA can improve the system of risk stratification in MM. Disclosures No relevant conflicts of interest to declare.

Adoption and utilization of NGS-based molecular profiling in community-based oncology practices: Insights from Sarah Cannon.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18064-e18064
Author(s):  
Andrew McKenzie ◽  
Daniel Schlauch ◽  
Yasha Sharma ◽  
David R. Spigel ◽  
Howard A. Burris ◽  
...  
Keyword(s):  
Clinical Care ◽  
Community Setting ◽  
Standard Of Care ◽  
Molecular Profiling ◽  
Community Based ◽  
Sequencing Technologies ◽  
Community Oncology ◽  
Medical Oncologists ◽  
Tumor Types ◽  
Ngs Data

e18064 Background: As the price of NGS-based sequencing technologies falls, adoption of those technologies is predicted to increase. To date, a survey of the adoption and utilization of NGS-based technologies as a part routine oncology clinical care has not been performed. Thus, a comprehensive analysis of physician adoption and utilization of commercial NGS testing in the community-setting between 2012 and 2018 was performed. Methods: Medical Oncologists in the Sarah Cannon Research Institute network ordered commercially-available NGS-based molecular profiling for their patients as standard of care. Data use agreements were initiated between SCRI, affiliated medical oncology practices, and commercial NGS testing providers, and patient NGS data were subsequently analyzed starting in 2012. Results: Community-based NGS testing rates within the Sarah Cannon network were 5.75/month in 2012 and 440/month in 2018. Plasma-based NGS testing began in 2014 and comprised 4.9% of total testing compared to 40.1% in 2018. The number of oncologists ordering molecular profiles increased from 11 in 2012 to 269 in 2018. Physician test utilization grew from an average of 6 tests/physician to 22 tests/physician in 2012 and 2018, respectively. NGS tests were performed on 34 different tumor types and biopsies were taken from both primary (~40%) and metastatic (~60%) sites . Tissue-based tests averaged 14 mutations/sample while plasma-based tests averaged 4 mutations/sample. There was a 74% decrease in median time between biopsy collection and NGS test results between 2012 and 2018 (131 and 34 days, respectively), indicating a shift toward the use of fresh – non-archival – tissue in recent years. Conclusions: These data establish NGS-based testing trends in community oncology practices and show that NGS-based tumor testing utilization has increased in the community-setting between 2012 and 2018. NGS testing is performed on a wide array of tumor types and oncologists utilize fresher biopsies.

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