scholarly journals Breakthrough Mucormycosis Developing on Mucorales-Active Antifungals Portrays a Poor Prognosis in Patients with Hematologic Cancer

2021 ◽  
Vol 7 (3) ◽  
pp. 217
Author(s):  
Dierdre B. Axell-House ◽  
Sebastian Wurster ◽  
Ying Jiang ◽  
Andreas Kyvernitakis ◽  
Russell E. Lewis ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Symptom Onset ◽  
Poor Prognosis ◽  
Treatment Initiation ◽  
Cox Regression ◽  
Severe Neutropenia ◽  
Apache Ii Score ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Cox Regression Analysis

Although breakthrough mucormycosis (BT-MCR) is known to develop on mold-active antifungals without Mucorales activity, it can also occur while on Mucorales-active antifungals. Herein, we retrospectively compared the characteristics and outcomes of patients with hematologic malignancies (HMs) or hematopoietic stem cell transplant (HSCT) who developed BT-MCR on mold-active antifungals with or without Mucorales activity. Of the patients developing BT-MCR, 16 were on Mucorales-active antifungals (9 isavuconazole, 6 posaconazole, 1 amphotericin B), and 87 were on other mold-active agents (52 voriconazole, 22 echinocandins, 8 itraconazole, 5 echinocandin + voriconazole). Both groups were largely comparable in clinical characteristics. Patients developing BT-MCR while on Mucorales-active antifungals had higher 42-day mortality, from either symptom onset (63% versus 25%, p = 0.006) or treatment initiation (69% versus 39%, p = 0.028). In multivariate Cox regression analysis, exposure to Mucorales-active antifungals prior to BT-MCR had a hazard ratio of 2.40 (p = 0.015) for 42-day mortality from treatment initiation and 4.63 (p < 0.001) for 42-day mortality from symptom onset. Intensive care unit (ICU) admission and APACHE II score at diagnosis, non-recovered severe neutropenia, active HM, and amphotericin B/caspofungin combination treatment were additional independent predictors of 42-day mortality. In summary, BT-MCR on Mucorales-active antifungals portrays poor prognosis in HM/HSCT patients. Moreover, improvements in early diagnosis and treatment are urgently needed in these patients.

scholarly journals Expression of LOX Suggests Poor Prognosis in Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinfeng Zhu ◽  
Chen Luo ◽  
Jiefeng Zhao ◽  
Xiaojian Zhu ◽  
Kang Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Expression Level ◽  
Cox Regression Analysis

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p &lt; 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.

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.

scholarly journals Effectiveness of antipsychotics used in first-episode psychosis: a naturalistic cohort study

BJPsych Open ◽  
2016 ◽  
Vol 2 (5) ◽  
pp. 323-329 ◽  
Author(s):  
Richard Whale ◽  
Michael Harris ◽  
Gail Kavanagh ◽  
Vijitha Wickramasinghe ◽  
Christopher I. Jones ◽  
...  
Keyword(s):  
Cohort Study ◽  
Treatment Initiation ◽  
Cox Regression ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Cox Regression Analysis ◽  
Episode Psychosis ◽  
Case Files ◽  
One Year ◽  
Risk Of Treatment

BackgroundOne year of antipsychotic treatment from symptom remission is recommended following a first episode of psychosis (FEP).AimsTo investigate the effectiveness of commonly used antipsychotic medications in FEP.MethodA retrospective cohort study of naturalistic treatment of patients (N = 460) accepted by FEP services across seven UK sites. Treatment initiation to all-cause discontinuation determined from case files.ResultsRisk of treatment discontinuation is greatest within 3 months of treatment initiation. Risperidone had longest median survival time. No significant differences were observed in time to discontinuation between commonly used antipsychotics on multivariable Cox regression analysis. Poor adherence and efficacy failure were the most common reasons for discontinuation.ConclusionsEffectiveness differences appear not to be a current reason for antipsychotic choice in FEP. Adherence strategies and weighing up likely adverse effects should be the clinical focus.

Long Noncoding RNAZEB1-AS1 Expression Predicts Progression and Poor Prognosis of Colorectal Cancer

2017 ◽  
Vol 32 (4) ◽  
pp. 428-433 ◽  
Author(s):  
Jining Fu ◽  
Yongyuan Cui
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Depth Of Invasion ◽  
Cox Regression Analysis ◽  
Lower Survival Rate ◽  
Differentiation Degree ◽  
Diagnostic Sensitivity And Specificity

Background ZEB1-AS1 acts as an oncogene in hepatocellular carcinoma, accelerating tumor growth and promoting metastasis. However, its roles in colorectal cancer (CRC) remain unclear. Methods In this study, we determined the expression of ZEB1-AS1 in CRC tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, we investigated the relationship between various clinicopathological features of CRC patients and ZEB1-AS1 expression, and evaluated the diagnostic and prognostic value of ZEB1-AS1 in CRC. Results We found that ZEB1-AS1 expression was significantly higher in CRC tissues than in adjacent normal colorectal tissues. Moreover, its expression was significantly correlated with tumor size, differentiation degree, TNM grade, metastasis, depth of invasion and Dukes' classification, but not with sex, age, location and organization. In addition, at the optimal cutoff value of 2.340, the values of diagnostic sensitivity and specificity amounted to 63.0% and 90.7%, respectively, with an area under the curve (AUC) of 0.846 (95% CI, 0.797-0.895). Finally, CRC patients of the high ZEB1-AS1 expression group had a poorer prognosis and a significantly lower survival rate than those of the low expression group, and Cox regression analysis indicated that ZEB1-AS1 expression and metastasis were independent predictors of poor prognosis. Conclusions Our data suggest that ZEB1-AS1 has no obvious early diagnostic value, but it may be utilized as a new prognostic biomarker for CRC.

High Thymidine Kinase Activity and CD5 Positivity Predict Poor Prognosis Of DLBCL Treated With R-CHOP

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5075-5075
Author(s):  
Kazuhito Suzuki ◽  
Yasuhito Terui ◽  
Masahiro Yokoyama ◽  
Noriko Nishimura ◽  
Naoko Tsuyama ◽  
...  
Keyword(s):  
Thymidine Kinase ◽  
Germinal Center ◽  
Poor Prognosis ◽  
Kinase Activity ◽  
Cox Regression ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
Thymidine Kinase Activity ◽  
Cox Regression Analysis ◽  
Two Factors

Abstract Introduction Thymidine kinase (TK) activity has been investigated as a prognostic factor in hematological malignancies, and several studies have demonstrated that high TK activity correlates with the disease stage and provides prognostic information on overall survival (OS) and progression-free survival (PFS). We have reported that high thymidine kinase activity (TK) predicts poor prognosis for diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP. In addition, CD5 positivity was reported as a poor predictor for DLBCL. The purpose of this retrospective study was to investigate the prognostic value of high TK activity and CD5 positivity compared with other laboratory findings in evaluating OS in patients undergoing R-CHOP for previously untreated DLBCL. Methods We retrospectively analyzed 176 patients newly diagnosed with DLBCL and treated with R-CHOP from September 2003 to October 2008 in our institute, and followed them until December 2012. The values of TK activity, CD5, non-germinal center type, C-reactive protein, lactate dehydrogenase, and beta2 microglobulin before R-CHOP were evaluated as prognostic factors for overall survival (OS). The cut-off of TK activity was defined as 14 IU/L because the median level of TK activity was 14.0 IU/L. CD5 positivity was defined if CD5 expression was detected by flow cytometry. Excluded were those positive for cyclin D1 or those with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma. Germinal center type was defined by Hans classifier. The primary endpoint was OS. First, the OS and PFS were analyzed by the Kaplan-Meier method, and biological prognostic factors for OS were evaluated by Cox regression analysis. Second, we classified the patients into three risk groups due to significant poor predictors. All reported p-values were two-sided, and statistical significance was defined as p < 0.05. Results Median age of the evaluable patients was 65.2 years old. The number of CD5+ patients was 19 (10.8%). The median levels of TK activity, CRP, LDH, and Hb were 14.0 IU/L (range, 3.0–1,100), 0.3 IU/L (range, 0.1–21.2), 254.5 IU/L (range, 111.0–44,432), and 13.1 g/dL (range, 7.7–17.0), respectively. Median follow-up was 60.0 months. Five-year OS rate of all patients was 51.1%. The OS was significantly worse in patients with high TK activity, CD5 positivity (CD5+), and high beta2 microglobulin level by univariate analysis. Five-year OS rates of the high-TK-activity arm and the low-TK-activity arm were 39.1% and 62.9%, respectively (p = 0.001). Five-year OS rates of the CD5+ arm and the CD5-negative arm were 21.1% and 53.8%, respectively (p = 0.002). The OS was significantly worse in patients with high TK activity and CD5+ by Cox regression analysis (hazard ratios 2.595 and 2.585; p = 0.044 and 0.026, respectively). We classified the patients into three groups based on the numbers with high TK activity and CD5+. There was a significant difference of OS in the three risk groups: five-year OS rates were 8.3% in the high-risk arm (two factors), 43.9% in the intermediate-risk arm (one factor), and 64.6% in the low-risk arm (zero factors) (p < 0.001). This prognostic model was suitable for PFS. Five-year PFS rates were 8.3% in the high-risk arm (two factors), 31.7% in the intermediate-risk arm (one factor), and 59.6% in the low-risk arm (zero factors) (p < 0.001). According to the chi square test and Fisher's exact test, there was no significant relationship between high TK and CD5+ (p = 0.153). Conclusions High TK activity and CD5+ were strong predictors of short OS in patients with newly diagnosed DLBCL treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.

Impact of Donor-Recipient Histocompatibility and CMV-Mismatch on Outcome of Allogeneic Stem Cell Transplantation for AML and MDS: A Retrospective Registry Study of the German Stem Cell Transplant Registry (DRST) of the German Working Group for Blood and Marrow Transplantation (DAG-KBT)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2304-2304 ◽  
Author(s):  
Francis A. Ayuk ◽  
Dietrich W. Beelen ◽  
Martin Bornhäuser ◽  
Matthias Stelljes ◽  
Tajana Zabelina ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Research Funding ◽  
Cox Regression ◽  
Negative Impact ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
T Cell Depletion ◽  
Cox Regression Analysis

Abstract Introduction Allogeneic stem cell transplantation (allo-SCT) is a curative treatment for several hematological diseases. Donor-recipient histo-incompatibility is associated with poorer outcome. Transplant outcome of CMV positive patients is reported to be poorer, if the unrelated donor is CMV negative (CMV-mismatch). Recent developments in transplant strategies including high resolution HLA-typing, toxicity-reduced conditioning regimens, CMV-monitoring, and improved supportive care have made transplants from HLA- as well as CMV- mismatched unrelated donors more feasible. We present a retrospective registry analysis from a large, and recent cohort of patients transplanted under these conditions. Patients and methods: We report data from adult recipients of allo-SCT treated between 2005 and 2013 in 10 transplant centers across Germany. Inclusion criteria were: 1.) consecutive patients from each center with AML or MDS as reported to the German Stem Cell Transplant Registry (DRST), 2) age >/= 18 years, 3) availability of high-resolution typing for HLA-A, -B, C, DRB1 and DQB1 in case of unrelated donor. Patients with ex-vivo T cell depletion were excluded. 3215 patients with AML (n = 2648) or MDS (n = 567) were included in the study. Donors were matched related (MRD, n =872), matched unrelated (MUD, n = 1553) or mismatched unrelated (9/10 MMUD, n= 620; 8/10 MMUD n = 137; <8/10 MMUD n = 33). Remission status at transplant was CR (49%), not in CR (40%) or untreated (11%). The vast majority of patients (96%) received peripheral blood stem cell grafts. Conditioning was reduced intensity (51%) or myeloablative (49%) according to EBMT criteria. ATG (56%) or alemtuzumab (8%) were used for in vivo T cell depletion. Median patient age was 56 (18-79) years. Median donor age was 38 (12-80) years. Median follow-up was 54 months (34-81 months). Primary endpoint was overall survival (OS) at 3 years. Results: Kaplan-Meier estimates for OS at 3 years was similar after transplants from MRD = 55% (95%CI 51-59%) compared to MUD = 53% (95%CI 51-59%), p = 0.26. OS at 3 years was worse for 9/10 MMUD with 45% (95% CI 41-49%, p<0.001), for 8/10 MMUD with 35% (95% CI: 27%-43%, p < 0.001) and for <8/10 MMUD with 29% (95% CI 13%-45%, p = 0.005) (figure 1). In recipients of unrelated donor transplants, multivariate cox regression analysis revealed significant negative impact of increasing patient age, increasing donor age, sex-mismatch (male patient/female donor), CMV-mismatch (patient pos/ donor neg), diagnosis of AML or sAML compared to MDS, lack of complete remission at transplant, abnormal cytogenetics and HLA-mismatching (table 1a). In a subgroup analysis restricted to patients transplanted from unrelated donors after myeloablative conditioning and T cell depletion, 3 years OS was better after 10/10 MUD: 60% (55-65%) compared to 9/10 MMUD: 49% (41-57%), p = 0.02. This was also true after reduced intensity conditioning and T cell depletion with ATG, with 3 year OS after 10/10 MUD: 49% (45-53) compared to 9/10 MMUD: 37% (31-43%), p = 0.001. Excluding HLA-DQB1-mismatches and HLA-C0303/0304-mismatches from the 9/10 MMUD group did not significantly alter results. Acknowledging the negative impact of both HLA and CMV-mismatching, we sought to determine which of these two parameters is of higher relevance for donor selection. For this purpose subgroup analyses were performed including only CMV-positive patients who received transplants from an unrelated donor (10/10 MUD or 9/10 MMUD). HLA-DQB1-mismatches and HLA-C0303/0304-mismatches were excluded. For this subgroup of n = 1167 patients multivariate cox regression analysis revealed better outcome after 10/10 MUD from CMV neg. donors compared to 9/10 MMUD from a CMV pos. donors (RR: 1.31, p = 0.04, table 1b and figure 2). Restricting the analysis only to patients who received T cell depletion with ATG did not significantly alter these findings. Conclusions: In this large multicenter cohort of recently transplanted patients, we find similar survival outcomes for matched related and fully matched unrelated donor transplants. We confirm the negative impact of HLA-mismatching on survival outcome, irrespective of conditioning intensity. Our results show that though CMV-mismatching is associated with poorer outcome, its relevance is secondary to HLA-mismatching. Acknowledgments: This work was supported by a research grant of the DKMS-Stiftung to FA and WB. Disclosures Stelljes: Pfizer: Consultancy. Kobbe:Jansen: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding. Kröger:Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

Excelent Option Therapy of BONE Marrow Failure in Fanconi Anemia Patients Withouth Full Match Donnor

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5075-5075 ◽  
Author(s):  
Lisandro L Ribeiro ◽  
Samantha Nichele ◽  
marco Antonio Bitencourt ◽  
Ricardo Petterle ◽  
Gisele Loth ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Bone Marrow Failure ◽  
Hematological Parameters ◽  
Severe Neutropenia ◽  
Cell Transplant ◽  
Variable Degree ◽  
Duration Of Treatment ◽  
Hematopoietic Stem ◽  
Hematological Response

Abstract The main cause of morbidity and mortality of FA pts is bone marrow failure (BMF), which usually arises in the first decade of life and progresses to transfusion dependence and severe neutropenia. Androgen treatment has been recommended for FA pts with BMF for whom there is no acceptable hematopoietic stem cell transplant donor. Oxymetholone and Danazol are frequently used in these pts. We retrospectively analyzed data on 67 FA pts who received oxymetholone or danazol for the treatment of their BMF. The starting dose was approximately 1mg/kg for oxy and 2-4mg/kg for danazol. The hematological parameters at the initiation of treatment were hemoglobin (Hb) < 8 g/dL and/or thrombocytes < 30.000/μl. Patients were diagnosed between 01.2005 and 01.2016. The median age was 10.5 ys (2.9 - 40ys). Gender: 39M/27F. The median duration of treatment was 18m (3m - 95m). Fifty-three patients (79%) showed hematological response and became transfusion independence at a median of 3 months after beginning oxymetholone (2-9m) and 5 months after danazol (4-7m). Two adult pts treated with danazol achieved total hematological response with 2.5mg/kg. Seven pts are stable after tapering and stopping androgen with a median follow up of 4 ys (6m-8.5ys). Fourteen pts did not respond to treatment (21%). Eleven pts received an HSCT and seven are alive and well. Three pts were not transplanted and two are alive but transfusion dependent and one pt died from CNS bleeding. All patients developed variable degree of virilization but it was more evident with oxymetholone therapy. Older age at starting therapy was related to less virilization. Conclusion: This study shows the largest number of FA pts treated with androgen up till now. Androgen is an effective and well-tolerated treatment option for FA pts who develop BMF with 79% of them showing transfusion free after 3-5 months. This response may give us time to search for better donors. Disclosures No relevant conflicts of interest to declare.

Risk factors for development of second primary malignancies (SPM) after autologous stem cell transplant (ASCT) for multiple myeloma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8038-8038
Author(s):  
Amrita Y. Krishnan ◽  
Matthew Mei ◽  
Canlan Sun ◽  
Jennifer Berano-Teh ◽  
Stephen J. Forman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
Cox Regression ◽  
Older Age ◽  
Second Primary ◽  
Cell Transplant ◽  
Cox Regression Analysis ◽  
Therapeutic Decisions ◽  
Increased Risk ◽  
Autologous Hct

8038 Background: Studies from the CALGB and IFM have suggested an increased incidence of SPM post ASCT in patients on lenalidomide maintenance. Patients with MM as well as patients post ASCT are inherently at higher risk of SPM. Therefore, assessment of risk factors associated with SPM would be useful in therapeutic decisions re preASCT therapy and post ASCTmaintenance. Methods: We conducted a retrospective cohort study of 841 consecutive MM patients who underwent at least one ASCT at City of Hope from 1989 to 2009. Sixty cases with 70 SPMs were identified. A nested case-control study was also conducted to understand the role of therapeutic exposures associated with SPMs. Controls were MM patients post ASCT matched by year of HCT (±5 years). Results: The median length of follow up was 3.3 yrs. (range 0.3-19.9). Median age at ASCT was 56 yrs (range 18-77). 62% had received a single autologous HCT, 27% tandem autologous HCT, 11% had received multiple HCTs (72 had a second allogeneic HCT)). The overall cumulative incidence of any SPM was 7.4% at 5 years and 15.9% at 10 years; the cumulative incidence of SPMs for patients >55 years approached 21.9% at 10 years. The cumulative incidence of MDS/AML was 1.8% and of solid tumors was 13.0%. Factors examined included age, race, sex, number and individual therapeutic exposures ( pre-ASCT, conditioning, and post-ASCT), disease status at ASCT. Multivariate Cox regression analysis revealed non-Hispanic whites (RR=2.4, 95% CI, 1.2-4.6, p=0.01) and older age (>55) at diagnosis of MM (RR=2.3, 95% CI, 1.3-4.1, p=0.004) to be associated with an increased risk of developing SPMs. Only cumulative thalidomide exposure (both pre-ASCT and post-ASCT) demonstrated a trend toward a positive association (OR=3.5, 95% CI, 0.6-19.4, p=0.15). Six patients (3 cases and 3 controls) were exposed to lenalidomide prior to development of SPM (OR=1.0, 95% CI, 0.14-7.10). Conclusions: This single institution analysis identified non-hispanic whites and older age to be associated with increased risk of developing SPM in pts post ASCT for MM. The trend towards increased risk with thalidomide exposure may be suggestive of a class effect from IMIDs that is not restricted to lenalidomide alone.

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