Cytogenetic Abnormalities Predict Clinical Outcome In Patients Diagnosed With Relapsed Acute Myeloid Leukemia (rAML): Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4955-4955
Author(s):  
Hassan Alkhateeb ◽  
Rhett P Ketterling ◽  
Niamh Keane ◽  
Mrinal M Patnaik ◽  
Animesh Pardanani ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Complete Remission ◽  
Clinical Outcome ◽  
Salvage Therapy ◽  
Prognostic Value ◽  
Clonal Evolution ◽  
Wilcoxon Test ◽  
Cell Transplant ◽  
Prognostic Role ◽  
Cytogenetic Abnormalities

Abstract Background Cytogenetic abnormalities have significant prognostic role in AML at the time of diagnosis. Several prognostic groupings have been recommended including the NCCN and European LeukemiaNet classification. It is still unknown whether cytogenetic abnormalities have any prognostic role at the time of relapse for predicting clinical outcome. In addition, clonal evolution (CE) has been seen in many AML cases, but its prognostic value remains to be identified. Aim To study cytogenetic abnormalities and clonal evolution impact on clinical outcome for patients diagnosed with rAML Method A retrospective, single institution study through chart review of all cases diagnosed with rAML at Mayo Clinic Rochester between 2003 to 2011 was performed. Pts who achieved complete remission and relapsed at our institution were included. Pts with PML-RARA and BCR-ABL rearrangements were excluded from this study. Pts with available cytogenetics data, both at presentation and relapse, were included. Response to treatment was defined as per international working group (IWG) criteria (Cheson JCO 2003). Appropriate IRB approval was obtained in accordance with Helsinki declaration. Comparison between groups’ medians was done using Wilcoxon test, while survival estimates were calculated using Kaplan-Meier curves using JMP V9. Results Out of 192 pts, 74 pts matched our inclusion criteria. The median age at diagnosis is 60 years (range 18-81), 53% were males. At relapse, median white blood cell (WBC) was 3.2 x109, hemoglobin 10.4 g/dL, platelet 59 x109, peripheral blood (PB) blast 2% (range, 0-96), bone marrow (BM) blasts 23% (range, 1-95) and cellularity 60%. Relapse site was mainly in the BM (95%). Flt3 mutation was found in 12/43 (28%), while NPM1 mutation in 2/7 (29%). Upon treatment with salvage therapy, 27 (36%) pts achieved complete remission (CR) and 16 (22%) pts partial remission (PR) for a total overall response (OR) of 58%. Twenty one (28%) pts were able to proceed to allogeneic stem cell transplant (SCT) after achieving remission. Median overall survival (mOS) was 198 days. Pts had a longer mOS if they proceeded to SCT (386 days vs 121 days, p =0.0003). Cytogenetic analysis (CG) were diploid in 32 (43%) of 74 pts at relapse. Five pts had favorable cytogenetics (3 pts with t(8,21) and 2 pts with inv (16)). CG was divided into favorable, intermediate and poor prognosis as per NCCN classification in 5 (7%), 45 (61%), 24 (32%), respectively. As per European LeukemiaNet, there were 4 CG groups divided into: favorable, Intermediate-1, intermediate-2, and adverse in 5 (7%), 33 (45%), 12 (16%), 24 (32%), respectively. Upon comparison of CG at diagnosis and relapse; clonal evolution (a change in CG due to gain or loss of chromosomal abnormalities) was found in 42/74 (57%) of pts. CG reverted back to diploid in 8/42 (19%) or gained additional CG abnormalities at relapse in 32 (76%) pts. CR2 was achieved in 80% of favorable CG (NCCN grouping), 40% (intermediate), and 21% in poor risk (p=0.01). Using NCCN CG grouping mOS was: 435 days (favorable), 266 (intermediate), and 104 (poor) (p value = 0.01). However, using European LeukemiaNet grouping mOS was: 435 days (favorable), 174 (intermeidtae-1), 363 (intermediate-2), and 104 (poor) (p=0.004). CE did not affect mOS (p =0.7). On multivariate analysis, response to salvage therapy (p<0.0001), NCCN CG grouping (p =0.03), wbc (p=0.045), and PB blasts (p=0.01) were significant but not age, BM blast, platelet and CE. Conclusion CG were diploid in 43% of relapsed pts. CE (gain or loss of cytogenetic abnormalities) was seen in 57% of CG at relapse compared to diagnosis but did not affect mOS. NCCN (and not European LeukemiaNet) cytogenetic grouping did affect clinical outcome through both achieving second CR and mOS (both on univariate and multivariate analysis). Our results confirm the prognostic value of CG on relapse, and need to be confirmed by larger studies.  Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prognostic Impact of Cytogenetic Abnormalities in Adult Patients with Philadelphia-Chromosome (Ph)-Negative Acute Lymphoblastic Leukemia (ALL) Who Underwent Allogeneic Stem Cell Transplant (allo-SCT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2024-2024
Author(s):  
Hiroaki Shimizu ◽  
Takayuki Saitoh ◽  
Shinichiro Okamoto ◽  
Yoshinobu Kanda ◽  
Heiwa Kanamori ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Complete Remission ◽  
Research Funding ◽  
Pharmaceutical Research ◽  
Patient Characteristics ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Cytogenetic Abnormalities ◽  
Significant Difference

Abstract Background: Cytogenetic abnormalities at diagnosis are recognized as a potent prognostic factor for acute leukemia patients. Among acute myeloid leukemia patients, the prognostic implications of cytogenetic abnormalities have been established for those treated with chemotherapy as well as those undergoing allo-SCT. In the context of Ph-negative ALLpatients, cytogenetic abnormalities at diagnosis clearly stratify the prognosis, whereas it has not been elucidated whether similar prognostic stratification is applicable to allo-SCT recipients. Objective: The aim of this retrospective study was to assess the prognostic impact of cytogenetic abnormalities in adult Ph-negative ALL patients who underwent allo-SCT. Patients and Methods: The study cohort included 373 adult Ph-negative ALL patients aged over 15 years who underwent allo-SCT for the first time between January 2001 and December 2012 at the 23 institutions participating in the Kanto Study Group for Cell Therapy (KSGCT). Patients' clinical data were collected from the KSGCT database. The Institutional Review Board of Gunma University approved the protocol of this study. Karyotypes considered high risk (HR) included t(4;11), t(8;14), low hypodiploidy, and complex (equal or more than five abnormalities), and all other karyotypes were designated standard risk (SR). On this basis, 308 patients (82.6%) were categorized as SR and 65 patients (17.4%) were categorized as HR at diagnosis. Of the 373 patients, 267 underwent allo-SCT in complete remission (CR) (224 in the SR group and 43 in HR group), and 106 in non-CR (84 in the SR group and 22 in HR group). For analysis, the study population was stratified based on disease status at the time of transplant. Almost all patients were conditioned with total body irradiation (TBI)-containing myeloablative conditioning (MAC) regimens prior to transplantation. Overall survival (OS) was defined as the interval from the date of transplantation to the date of death. Non-relapse mortality (NRM) was defined as any death in continuous complete remission (CR). The Fisher's exact test was used for comparison of binary variables. OS and RFS were estimated by the Kaplan-Meier method, and compared using the log-rank test. Cumulative incidences (CI) of relapse and NRM were compared using the stratified Gray test. P < 0.05 was considered as statistically significant. Results: [Patients in CR] No significant difference in patient characteristics and transplant procedures was observed between the SR and HR groups. The 5-year OS rates were similar between the SR and HR groups (60.5% vs. 74.1%, respectively; p = 0.225) (Figure 1). Similarly, there were no significant differences in the 5-year CI of relapse and NRM rates between the two groups (relapse: 26.3% vs. 24.8%, respectively; p = 0.498, NRM: 19.6% vs. 10.0%, respectively; p = 0.232). Multivariate analysis for OS identified MAC and TBI-containing regimens, not cytogenetic risk, as significant positive prognostic factors. [Patients in non-CR] No significant difference was observed between the SR and HR groups in terms of patient characteristics or transplant procedures, although there was a female predominance in the HR group. Patients in the SR group had a significantly superior 5-year OS rate compared to the HR group (15.4% vs. 4.5%, respectively; p = 0.022). There was no significant difference in the 5-year CI of relapse between the SR and HR groups (60.3% vs. 50.0%, respectively; p = 0.411), whereas the 5-year CI of NRM in the SR group was significantly lower than that in the HR group (24.8% vs. 45.5%, respectively; p = 0.024). Multivariate analysis revealed cytogenetic risk group as an independent prognostic factor. Conclusion: These findings suggest that adult Ph-negative ALL patients in remission with HR cytogenetic abnormalities have similar transplant outcomes to those in the SR group. Considering the reported equality of the CR rates between the two groups, allo-SCT at an early clinical phase is recommended for HR group patients, reminiscent of Ph-positive ALL patients in the pre-imatinib era. Current transplant procedures do not improve outcomes for patients who are not in remission, especially those with HR cytogenetic abnormalities. Disclosures Usuki: MSD: Other: personal fees, Research Funding; SymBio Pharmaceutical: Other: personal fees, Research Funding; GlaxoSmithKline: Other: personal fees, Research Funding; Shionogi: Other: personal fees; Fujimoto Pharmaceutical: Research Funding; Bristol-Myers Squibb: Other; Takeda Pharmaceutical: Research Funding; Nippon Shinyaku: Other: personal fees, Research Funding; Sanofi: Other: personal fees, Research Funding; Shire: Research Funding; Kyowa Hakko Kirin: Other: personal fees, Research Funding; Otsuka Pharmaceutical: Research Funding; Eisai: Research Funding; Novartis: Other: personal fees, Research Funding; Boehringer Ingelheim: Other: personal fees, Research Funding; Celgene: Other: personal fees, Research Funding; Sumitomo Dainippon Pharma: Other: personal fees, Research Funding; Chugai Pharmaceutical: Other: personal fees; Fuji Film RI Pharma: Other: personal fees; Taiho Pharmaceutical: Other: personal fees, Research Funding; Astellas: Research Funding. Nakaseko:Novartis: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Otsuka: Honoraria, Research Funding.

scholarly journals Expanding the Indications for Ibrutinib: Complete Remission Obtained By Induction with Ibrutinib Followed By Consolidative Ahsct in Refractory Primary CNS Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5631-5631 ◽  
Author(s):  
Cassidy Brothers
Keyword(s):  
Complete Remission ◽  
Disease Progression ◽  
Salvage Therapy ◽  
B Cell Lymphoma ◽  
Salvage Treatment ◽  
Severe Neutropenia ◽  
High Dose ◽  
Cell Transplant ◽  
Curative Intent ◽  
Hematopoietic Stem

Introduction Primary central nervous system lymphoma (PCNSL) is an exceedingly rare and aggressive sub-type of Non-Hodgkin's Lymphoma. Despite initial polychemotherapy that includes High-Dose Methotrexate (HD-MTX), over half of patients will develop recurrent or refractory disease that requires salvage therapy.1 Ibrutinib, a Bruton's tyrosine kinase inhibitor, has become an alternative for salvage treatment in relapsed or refractory PCNSL (RR-PCNSL) that is particularly useful in patients who are ineligible for re-induction with HD-chemo. In RR-PCNSL, Ibrutinib led to a progression free survival (PFS) of roughly 5 months when used as monotherapy2,3 and 15 months when used as add-on therapy.4 While its role as salvage treatment has been documented, its use to facilitate consolidative autologous hematopoietic stem cell transplant (AHSCT) in RR-PCNSL is not currently known. The following case describes the first known report of a patient with RR-PCNSL who achieved persistent complete remission following Ibrutinib salvage treatment and consolidative AHSCT. Case Description A 64-year-old male presented to the emergency department with a two-week history ptosis, visual abnormalities, confusion, and increasing fatigue. On physical exam, he was found to have bilateral mydriasis, left third nerve cranial palsy, severe left-sided ptosis, and restricted upwards and downward gaze of the right eye. A contrast-CT was performed which showed multiple areas of abnormal enhancement throughout the frontal lobes, corpus callosum, and midbrain associated with significant vasogenic edema. These findings were confirmed on MRI. He underwent a stereotactic guided burr hole biopsy which was consistent with diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry performed on the tissue showed that the neoplastic cells were CD3(-), CD5(-), CD20(+), CD10(-), BCL2(subset +), BCL6(+), MUM1(+) and Cyclin D1(-). Staging CT and bone marrow biopsy showed no evidence of systemic disease. He was diagnosed with PCNSL and went on to receive induction therapy with Rituximab, Methotrexate, Procarbazine, and Vincristine (R-MPV) with curative intent and received a total of 7 cycles. Initially, he had a significant radiographic response with a repeat MRI post cycle 4 showing only a few small areas of residual enhancement. However, after completion of the 7 cycles of R-MPV, his MRI showed evidence of disease progression with both new and enlarging intra-axial lesions. Given his ECOG of 0 and lack of comorbidities, it was decided that he would proceed with salvage treatment with Cytarabine and Etoposide with curative intent for refractory PCNSL. Unfortunately, after only four weeks of receiving cycle one of Cytarabine and Etoposide, a repeat MRI showed evidence of disease progression. He was then transitioned to palliative therapy with prednisone up until December 2017, at which point he was able to obtain Ibrutinib on a compassionate basis. He was started on Ibrutinib salvage therapy and achieved radiographic evidence of complete remission after four months of treatment. There were minimal adverse effects of Ibrutinib therapy, most notably a severe neutropenia requiring a temporary discontinuation of therapy for two weeks. He underwent consolidative AHSCT with Thiotepa, Busulfan and Melphalan conditioning in August 2018. His post-transplant course was complicated by culture negative febrile neutropenia with a subsequent source determined to be Clostridium difficile for which he was treated. An MRI head performed 3 months after his AHSCT showed no evidence of recurrent or residual disease. He continues to be followed by the Hematology Service in Newfoundland and has remained in complete remission since. Conclusions This case demonstrates the feasibility of a salvage approach using Ibrutinib followed by AHSCT when standard salvage options have been exhausted in refractory PCNSL. OffLabel Disclosure: Ibrutinib's indications do not currently include use as a induction treatment prior to AHSCT in refractory/recurrent PCNSL.

Outcome of Adults with Acute Lymphocytic Leukemia (ALL) with Second Salvage Therapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3966-3966
Author(s):  
Susan O’Brien ◽  
Deborah Thomas ◽  
Farhad Ravandi-Kashani ◽  
Stefan Faderl ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Platelet Count ◽  
Prognostic Factors ◽  
Salvage Therapy ◽  
Stem Cell Transplant ◽  
Survival Rates ◽  
Lymphocytic Leukemia ◽  
Cell Transplant ◽  
Factors Associated ◽  
One Year

Abstract Background and Aims. The outcome of adults with ALL undergoing second salvage therapy is poorly characterized. The aim of this study was to determine the outcome and prognostic factors associated with second salvage therapy in patients with ALL. Study Group and Methods. A total of 288 patients treated for ALL in second salvage at our institution were analyzed. Results. 53 patients (18%) achieved complete remission (CR). The median remission duration was 7 months. The median survival was 3 months. By multivariate analysis, prognostic factors independently associated with achievement of CR were: duration of first CR, and platelet count. Patients with a first CR &lt; 36 months and a platelet count &lt; 50 × 109/L had an expected CR rate of 7%. By multivariate analysis, prognostic factors independently associated with survival were: duration of first CR, percent of marrow blasts, platelet count, and albumin levels. Expected 12-month survival rates for patients with 0–1, 2, 3, or 4 adverse factors were 33%, 14%, 8%, and 0%, respectively. A repeat multivariate analysis using landmark assessment at 6 weeks selected achievement of CR as adding significantly to the survival benefit (p = 0.0001, hazard ratio 0.51). Only 22 patients (8%) were able to undergo allogeneic stem cell transplant as second salvage therapy; their one-year survival rate was 18%. Conclusions. The outcome of adults with ALL undergoing second salvage therapy is poor. Novel effective therapies against ALL are needed in this subset of patients.

scholarly journals Prognostic Impacts of Additional Cytogenetic Abnormalities Acquired at the First Relapse in Adult Patients with Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplant in Second Complete Remission

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3380-3380
Author(s):  
Hiroaki Shimizu ◽  
Junichi Mukae ◽  
Naoki Shingai ◽  
Takashi Toya ◽  
Yuho Najima ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Statistical Significance ◽  
Cell Transplant ◽  
Reduced Intensity Conditioning ◽  
Cytogenetic Abnormalities ◽  
Cytogenetic Changes ◽  
Conditioning Regimens ◽  
First Relapse

Abstract Background: Additional cytogenetic abnormalities (ACA), the most frequent form of cytogenetic changes, are considered as a result of genetic instability and clonal evolution of leukemia cells. Recently, we described that ACA at the first relapse was associated with the significantly lower second complete remission (CR2) rate and poor survival in adult acute myeloid leukemia (AML) patients (Hematol Oncol. 2018;36:252-257). However, the prognostic impact of ACA after allogeneic stem cell transplant (allo-SCT) has not been elucidated in adult AML patients. Patients and methods: Of the 145 adult AML patients who underwent the first allo-SCT in CR2 between 1997 and 2019, 98 patients whose cytogenetic abnormality data both at diagnosis and at the first relapse were available were included in this study. Cytogenetic changes between at diagnosis and the first relapse were classified into four groups: (1) no change, (2) ACA was acquired at the first relapse, (3) cytogenetic abnormalities observed at diagnosis were reduced or had disappeared at the first relapse, and (4) cytogenetic abnormalities observed at diagnosis were reduced or had disappeared, and completely different ACA was acquired at the first relapse. In this study, groups 2 and 4 were defined as ACA acquisition. Overall survival (OS) was defined as the interval from the date of transplant to the date of death. Fisher's exact test was used to compare binary variables. The cumulative incidence (CI) of non-relapse mortality (NRM) and relapse were evaluated with Gray's test, considering relapse and NRM as a competing risk, respectively. OS was estimated with the Kaplan-Meier method and compared using the log-rank test. Factors associated with at least borderline significance (p &lt; 0.20) in univariate analyses were subjected to multivariate analysis. The Cox and Fine-Gray proportional hazard model were used for multivariate analysis of prognostic and risk factors, respectively. Values of p &lt; 0.05 were considered to indicate statistical significance. Results: Of the 98 patients included in this study, 57 were male, and 41 were female. The median age at transplant was 45 years (range, 17-71 years). The median duration of CR1 was 12.4 months (range, 1.3-70.3 months) and cytogenetic risk groups were good, intermediate, and poor in 26 (27%), 70 (71%), and two patients (2%), respectively. Donor types were related, unrelated, and cord blood in 23 (24%), 59 (60%), and 16 patients (16%), respectively, and 86 (87%) and 61 patients (62%) were conditioned with myeloablative and total body irradiation-containing regimens, respectively. According to the definition described above, 20 patients (20%) acquired ACA at the first relapse. There was no significant difference in baseline characteristics and transplant procedures between patients with and without ACA acquisition. The OS rates were not significantly different between two groups (55% vs. 72% at three years after transplant; p = 0.28). The CI of relapse was significantly higher in patients with ACA acquisition than those without ACA acquisition (59% vs. 15%; p &lt; 0.01), while the CI of NRM were not significantly different between two groups (5% vs. 19%; p = 0.17). Multivariate analysis for OS revealed that age over 50 years (hazard ratio [HR] = 2.4; p &lt; 0.01), but not ACA acquisition, was identified as an independent prognostic factor. ACA acquisition (HR = 4.7; p &lt; 0.01) was extracted as an independent risk factor of relapse, while use of reduced intensity conditioning regimens (HR = 3.1; p = 0.03) and more than or equal to 1 of performance status at transplant (HR = 2.7; p = 0.04) showed independent risks of NRM. The similar OS rates between two groups might resulted from an offset of the lower relapse rate with the higher NRM rate in patients without ACA acquisition despite not reaching statistical significance. This increasing NRM rates in those without ACA acquisition was potentially associated with use of reduced intensity conditioning regimens in larger proportion (0% vs. 15%; p = 0.12). Conclusion: These findings suggested that ACA acquisition at the first relapse was associated with a higher risk of relapse even after allo-SCT in CR2 in adult AML patients. As AML cells with ACA acquisition was resistant to not only chemotherapy but also graft-versus-leukemia effect, innovative therapeutic strategy is warranted. Disclosures Handa: Janssen: Honoraria; Kyowa Kirin: Research Funding; Takeda: Honoraria, Research Funding; BMS: Honoraria; Chugai: Research Funding; Ono: Honoraria; Sanofi: Honoraria, Research Funding; Abbvie: Honoraria; MSD: Research Funding; Shionogi: Research Funding; Celgene: Honoraria, Research Funding; Daiichi Sankyo: Research Funding.

scholarly journals Clinical Significance of Clonal Cytogenetic Heterogeneity (CCH) at Diagnosis in Adult Patients with Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2820-2820
Author(s):  
Hiroaki Shimizu ◽  
Nahoko Hatsumi ◽  
Satoru Takada ◽  
Takuma Ishizaki ◽  
Akihiko Yokohama ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Research Funding ◽  
Clonal Evolution ◽  
Statistical Significance ◽  
Prognostic Impact ◽  
Common Ancestry ◽  
Complex Karyotype ◽  
Abnormal Karyotype ◽  
Cytogenetic Abnormalities

Abstract Background:Although cytogenetic abnormalities at diagnosis are recognized as one of the most potent prognostic factors in acute leukemia patients, CCH acquisition at diagnosis, which are considered as a result of clonal evolution of leukemia cells, is not taken into account in prognostic classifications. Recent studies reported that CCH acquisition was observed in 24 - 32% of adult AML patients with abnormal karyotype, was more likely to occur in patients with older age and complex karyotype, and showed adverse prognostic impact. However, the clinical significance of CCH acquisition has not been investigated in adult ALL patients to date. Patients and methods: Of the 238 adult ALL patients diagnosed between 1990 and 2016, 120 patients with abnormal karyotype at diagnosis, who underwent intensive chemotherapy, were included in this study. CCH was defined as presence of two or more cytogenetically abnormal clones. A defined ancestral clonal evolution included either mother-daughter and/or branched patterns. In the mother-daughter pattern, a daughter clone showed all cytogenetic abnormalities of a mother clone plus additional abnormality(s), which define a distinct subclone. In a branch pattern, all subclones possessed common cytogenetic abnormalities suggesting presence of a common ancestry, but each subclone acquires unique additional abnormality(s), which define them as distinctive subclones. Both patterns of cytogenetic clonal evolution were sometimes seen in a patient. Composite karyotypes were applied to patients where a common ancestry could not be clearly determined because of too complicated cytogenetic findings. Fisher's exact test was used to compare binary variables. The logistic regression model was used for multivariate analysis of predisposing factors. Overall survival (OS) was estimated with the Kaplan-Meier method and compared using the log-rank test. The Cox proportional hazard model was used for multivariate analysis of prognostic factors. Values of p < 0.05 were considered to indicate statistical significance. Results:Of the 120 patients included in this study, 64 patients were male, and 56 were female. The median age was 50 years (range, 16-79 years). Karyotypes at diagnosis were Philadelphia chromosome (Ph) in 56 patients, complex in 15, and t(8;14) in seven. According to the definition described above, 47 patients (39%) showed CCH at diagnosis, and two (4%) among them were categorized as composite karyotype. Of the 45 patients harboring a defined ancestral clonal evolution, numbers of subclones were two, three, and four in 32 patients (68%), 11 (24%), and 2 (4%), respectively. Mother-daughter pattern, branched pattern, and both were seen in 34 patients (76%), 5 (11%), and 6 (13%). In univariate analysis for predisposing factors of CCH acquisition, only younger age was significantly associated with CCH acquisition (48% in age <= 50 vs. 29% in age > 50; p = 0.04), but not karyotype. This statistical significance was confirmed with multivariate analysis (odds ratio = 0.44; p = 0.03). When investigating the prognostic impact of CCH acquisition, patients were divided into Ph-negative or Ph-positive ALL groups. In the 64 Ph-negative ALL patients, the CR rates were not significantly different between patients with or without CCH (78% vs. 78%, respectively; p = 1.00). The OS rates were similar between two groups (26% vs. 39% at five years, respectively; p = 0.56). Multivariate analysis for OS revealed that complex karyotype and t(8;14) were independent prognostic factors, but not CCH acquisition. Likewise, in the 56 Ph-positive ALL patients, CCH acquisition was not significantly associated with the CR rates (92% vs. 78%, respectively; p = 0.27), and the OS rates did not significantly differ between the two groups (34% vs. 40% at five years, respectively; p = 0.90). In multivariate analysis for OS, no independent prognostic factor was identified. Conclusion: Adult ALL patients with abnormal karyotype acquired CCH at diagnosis with a frequency comparable to that of AML patients. However, unlike AML patients, CCH acquisition was more frequently observed in younger population and did not show any prognostic impact in ALL patients. These findings suggested that biological backgrounds of CCH acquisition at diagnosis were possibly different between in patients with ALL and AML. So, to confirm these important findings, clinical studies with larger study subjects are warranted. Disclosures Handa: Celgene: Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Exploring the Prognostic Role of Ki67 Proliferative Index in Merkel Cell Carcinoma of the Skin: Clinico-Pathologic Analysis of 84 Cases and Review of the Literature

2020 ◽  
Vol 31 (4) ◽  
pp. 392-400 ◽  
Author(s):  
Stefano La Rosa ◽  
Matteo Bonzini ◽  
Amedeo Sciarra ◽  
Sofia Asioli ◽  
Roberta Maragliano ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Youden Index ◽  
Merkel Cell ◽  
Prognostic Role ◽  
Proliferative Index

AbstractThe exact prediction of outcome of patients with Merkel cell carcinoma (MCC) of the skin is difficult to determine, although several attempts have been made to identify clinico-pathologic prognostic factors. The Ki67 proliferative index is a well-known marker routinely used to define the prognosis of patients with neuroendocrine neoplasms. However, its prognostic value has been poorly investigated in MCC, and available published results are often contradictory mainly because restricted to small series in the absence of standardized methods for Ki67 evaluation. For this reason, we explored the potential prognostic role of Ki67 proliferative index in a large series of MCCs using the WHO standardized method of counting positive cells in at least 500 tumor cells in hot spot areas on camera-captured printed images. In addition, since MCC may be considered as the cutaneous counterpart of digestive neuroendocrine carcinomas (NECs), we decided to stratify MCCs using the available and efficient Ki67 threshold of 55%, which was found prognostic in digestive NECs. This choice was also supported by the Youden index analysis. In addition, we analyzed the prognostic value of other clinico-pathologic parameters using both univariate and multivariate analysis. Ki67 index appeared significantly associated with prognosis at univariate analysis together with stage IV, lack of MCPyV, and p63 expression, but not at the multivariate analysis, where survival resulted independently influenced by p63 expression and tumor stage, only.

Prognostic Value of Tumor-Infiltrating Lymphocytes in Schistosomiasis-Associated Colorectal Cancer

2021 ◽  
Author(s):  
Weixia Wang ◽  
Yingyi Zhang ◽  
Jican Liu ◽  
Hongyan Jing ◽  
Kui Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Lymph Nodes ◽  
Vascular Invasion ◽  
Prognostic Value ◽  
Tumor Budding ◽  
Prognostic Role ◽  
Infiltrating Lymphocytes

Abstract Aim: To investigate the relationship between schistosomiasis and tumour infiltrating lymphocytes (TILs), and the prognostic value of TILs in schistosomal colorectal cancer (CRC).Background: The association between TILs and CRC has long been suggested in the literature, but the association between TILs and schistosomiasis and the prognositic role of TILs in schistosomal CRC has never been reported previously.Methods: Hematoxylin and eosin (H&E)-stained sections of 351 CRC tumours, which were completely resected, were evaluated for density of TILs in intratumoural (iTIL) and stromal compartments (sTIL). Its relationship with clinicopathological features, including schistosomiasis, and clinical outcomes were evaluated and the prognostic role of sTILs in schistosomal CRC was explored.Results: Stromal TILs infiltration were correlated with smaller tumor size，less deeper pathological T stage, absence lymph node metastasis and less number of tumor budding (p＜0.05). However, there were no association between sTILs and shicstosomiasis. In the whole cohort, multivariate analysis identified gender, TNM Stage, Schistosomiasis, sTILs, lymph vascular invasion, lymph nodes positive for CRC were independent prognostic factors that associated with overall survival (OS) in CRC (p < 0.05). Patients were divided into two groups based on schistosomiasis infection status: colorectal cancer associated with schistosomiasis (CRC-NS set) and colorectal cancer without schistosomiasis (CRC-S set ). In the CRC-NS set, multivariate analysis demonstrated that tumor budding, sTILs, lymph vascular invasion, lymph nodes positive for CRC were independent prognostic factors that associated with OS (p < 0.05). However, there were no association between sTILs and OS in CRC-S set (p＞0.05). Besides, sTILs were associated with favorable OS in CRC-NS patients but not in CRC-S patients, regardless of age. Conclusion: Stromal TILs in the whole cohort and in the CRC-NS set were identified as an independent prognostic factor, but it was lack of prognostic role in schistosomal CRC. Stromal TILs was associated with less aggressive tumor features. Stromal TILs was associated with OS in CRC-NS patients but not in CRC-S patients, regardless of age.

Prognostic Role of Transfusion Requirement and Validation of the IPSS Prognostic System in Myelodisplastic Syndromes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2622-2622
Author(s):  
Flavia Salvi ◽  
Daniela Gioia ◽  
Daniela Cilloni ◽  
Ernesta Audisio ◽  
Margherita Bonferroni ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Transfusion Requirement ◽  
Laboratory Data ◽  
Prognostic Role ◽  
Cytogenetic Abnormalities ◽  
Prognostic System ◽  
Poor Outcome ◽  
Transfusion Requirements ◽  
Blast Count

Abstract BACKGROUND. The International Prognostic Scoring System (IPSS) of myelodysplastic syndromes (MDS) is based on bone marrow blast count, cytogenetic features and number of peripheral cytopenias. Transfusion requirement has been recently proposed as an important risk factor (Malcovati et al JCO23, 7594, 2005), and a new prognostic system (WPSS) has been suggested, based on WHO diagnostic subgroups, cytogenetic abnormalities and transfusion requirements (2005 ASH meeting abs.789). AIM OF THE WORK. To confirm the prognostic role of transfusion requirement and to compare the prognostic value of WPSS to that of IPSS. PATIENTS AND METHODS. The Piedmont MDS register is active since 1999. Clinical and laboratory data of patients were centrally recorded through our web site. Transfusion requirement data were retrospectively obtained from blood banks when possible. IPSS was calculated according to Greenberg et al. (Blood 89, 2079Blood 89, 1997). WPSS was calculated according to Malcovati et al. (2005 ASH meeting abst 789) by summing the score values of the following three variables: cytogenetic abnormalities scored according to the IPSS: 0 for good; 1 for intermediate; 2 for poor; transfusion requirement: 0 for absent; 1 for regular; WHO category: 0 for RA, RARS, 5q-, and unclassifiable; 1 for RCMD and RCMD-RS; 2 for RAEB-I; 3 for RAEB-II. WPSS score values were stratified into the proposed five risk groups: very low (score 0), low (1); intermediate (2); high (3–4); very high (5–6). RESULTS. From June 1999 to December 2004, 762 MDS patients were registered from 37 different institutions. Transfusion information was available for 376 patients. Data on both cytogenetics and transfusion requirements were available for 202 patients who are the object of the present analysis. 132 patients (65 %) needed regular transfusions, while the remaining 70 ones (35 %) did not. In univariate analyses all variables of both IPSS and WPSS scoring systems statistically influenced overall survival (OS). The time from diagnosis to the first transfusion was variable: less than six months in 97 cases (48 %); 6 to 12 months in 15 (7 %); more than 12 months in 20 (10 %). The OS of the 132 transfused patients was significantly worse than that of the 70 non-transfused ones, but the OS of patients who began to require transfusions more than 12 months after diagnosis was not significantly worse than that of not transfused patients. Only patients with an early transfusion requirement (within the first 12 month) had a poor outcome. When considering the prognosis of WHO subgroups the difference in OS between the subgroups 0 and 1 did not reach a significant level (p>0.05). In stepwise multivariate analysis the best prognostic factors were blast count, peripheral cytopenias and cytogenetic abnormalities. When the IPSS variables were included into the Cox model, neither WHO subgroups nor transfusion requirement retained an independent prognostic value. CONCLUSIONS. The prognostic value of transfusion requirement was confirmed, but only patients requiring transfusion within the first 12 months since diagnosis showed a poor outcome. In our experience IPSS model fits prognosis better than WPSS.

Detection of Cytogenetic Abnormalities Associated with Outcome Differences in Acute Myeloid Leukemia Using Array-Based Comparative Genomic Hybridization (aCGH) Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1633-1633
Author(s):  
Keyur Patel ◽  
Farhad Ravandi ◽  
Deqin Ma ◽  
Hui Yao ◽  
Ronald Abraham ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Clinical Outcome ◽  
Conflicts Of Interest ◽  
Comparative Genomic ◽  
Poor Overall Survival ◽  
Cytogenetic Abnormalities ◽  
Acgh Analysis ◽  
Kaplan Meier ◽  
Acute Myeloid

Abstract Abstract 1633 Poster Board I-659 Background The presence of abnormal cytogenetic findings at diagnosis is an independent indicator of the outcome in patients with acute myeloid leukemias (AML). Recent availability of high-resolution analysis by aCGH technology has facilitated rapid detection of cytogenetic abnormalities previously undetected by the conventional G-banded karyotyping. Aim: To determine whether specific cytogenetic abnormalities, as detected by the aCGH analysis, are associated with differences in clinical outcomes in a group of patients with AML treated uniformly with the standard chemotherapy regimen of Idarubicin and Cytarabine. Methods A total of 111 patients with newly diagnosed AML (Median age: 55 years; range, 22 to 73 years) were enrolled in the study. All patients were treated with Idarubicin 12 mg/m2 IV daily x 3 days and Cytarabine 1.5 g/m2 by continuous IV infusion daily x 4 days (3 days in patients older than 60). The diagnostic bone marrow samples from 48 of these patients were analyzed by aCGH using a 44K CGH array with a spatial resolution of 50-75 kb (Agilent Inc). The aberrations detected by aCGH using CGH Analytics (Agilent Inc, Santa Clara, CA) and the Nexus Copy Number Software (Biodiscovery Inc, El Segundo, CA) were compared to conventional G-banded karyotyping results. Correlation of aCGH-detected aberrations with clinical outcome was performed by Kaplan-Meier analysis and log-rank test. Results Complete remission (CR) was achieved in 34/48 (71%) patients, out of which 16 (47%) patients relapsed in less than 1 year (Median: 18.5 weeks, range: 1-44 weeks) and the remaining 18 (53%) patients sustained CR beyond one year (Median: 89 weeks, range: 58-132 weeks). The comparison of aCGH findings between the patients achieving CR and the resistant patients showed significant association of loss of a 155 kilobase region on 5q33.3 with achievement of CR (p<0.05). This 5q33.3 locus harboring two genes, transcription factor EBF1 and transmembrane protein RNF145, was deleted in 9/34 (26.5%) patients achieving CR, but not in the resistant patients (0/14, 0%). Additionally, the loss of 17p11.2-q11.1 spanning 3194 kilobases was associated with poor overall survival (Kaplan-Meier analysis, p=0.0096). This deleted region involved 342 genes and 12 microRNAs. Conventional karyotyping detected loss of 17p in 10/48 (21%) patients, whereas the aCGH analysis detected 17p losses in two additional patients (12/48, 25%). By allowing delineation of the precise boundaries of the aberrations, aCGH demonstrated that deletion of 17p did not involve the TP53 gene in 3/12 (25%) patients, although these three patients showed genetic instability and poor clinical outcome. Overall, the aCGH findings were in concordance with the conventional karyotyping results. The aCGH analysis was able to detect aberrations in samples containing blast count as low as 5%. In addition, aCGH identified previously undetected aberrations, as small as 5 kb, of currently unknown significance. Conclusion The aCGH analysis indicates that the loss of 5q33.3 is associated with achievement of complete remission and the loss of 17p11.2-q11.1 is associated with poor overall survival in AML patients treated with Idarubicin and Cytarabine. Array CGH analysis provides a useful and rapid diagnostic tool for identifying these high-risk patients. The biologic roles of EBF1 and RNF145 in therapy response warrant further investigation. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document