[Show abstract][Hide abstract] ABSTRACT: Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel.Bone Marrow Transplantation advance online publication, 7 December 2015; doi:10.1038/bmt.2015.300.
Full-text · Article · Dec 2015 · Bone marrow transplantation
[Show abstract][Hide abstract] ABSTRACT: Objective:
Human chitotriosidase (ChT) is an active chitinase expressed by activated phagocytes. Increased ChT activity has been reported in systemic Candida albicans infections and in Gram-negative and Gram-positive bacterial infections, indicating that an increase in ChT activity reflects phagocyte activation. The aim of this study was to determine the changes in serum ChT activity in patients who underwent high dose chemotherapy (HDC) and stem cell transplantation (SCT), who are at an increased risk for fungal and bacterial infections due to depression of the immune system during the neutropenic period.
Patients and methods:
A total of 55 SCT patients were included in the study. Serum ChT activity was determined before the initiation of HDC and during the neutropenic period after hematopoietic stem cell reinfusion on post-transplant first, fifth and tenth days.
Chitotriosidase levels before transplantation were significantly lower than the results at first, fifth and tenth days post-hematopoietic stem cell reinfusion.
Although the number of neutrophils was low, ChT enzyme activity was high in newly produced granules of neutrophils. Chitotriosidase may be supplemented as a drug for preventing and treating infections in the near future.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To evaluate the prognostic impact of response to induction chemotherapy preceding salvage HDCT courses, and prior paclitaxel therapy for advanced GCT. This knowledge can help refining the prognosis of patients receiving HDCT.
Twenty-four European centers contributed data. Eligibility included adult male patients with GCT, and treatment with salvage HDCT between the years 2002 and 2012.
Both paclitaxel used in prior lines of therapy and in induction-mobilization regimens pre-HDCT were considered. Multivariable Cox analyses of prespecified factors were undertaken on progression-free (PFS) and overall survival (OS). Missing data were handled by multiple imputation.
Since 10/2013, 324 of 442 registered pts were suitable for present analysis. One hundred ninety-two patients (59.3%) have received paclitaxel-containing regimens. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 [9%] missing or GCSF only). Median follow up was 36 months (IQR: 19-70).
Progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS in the univariable model (p<0.001 and p=0.032). However, on multivariable analysis from the model with fully available data (N=216) while progression to induction chemotherapy was significantly prognostic for PFS and OS (HR: 1.92, 95%CI, 1.24-2.98, and HR: 2.09, 95%CI, 1.27-3.42), prior paclitaxel therapy was not: HR: 1.10 (95%CI, 0.70-1.73, p=0.674) and HR: 1.09 (95%CI, 0.64-1.86, p=0.739), respectively. Results were confirmed by the model with imputed data. No significant interaction was found between prior paclitaxel therapy and taxane-containing HDCT (p=0.221 and p=0.077 for PFS and OS).
While progression to induction chemotherapy was independently prognostic, prior paclitaxel was not. Stratification of trials for the latter factor did not appear to be required when accounting for the other clinical predictors.
Keywords: Testicular neoplasms; Germ cell cancer; High-dose chemotherapy; Paclitaxel; Prognostic factors.
[Show description][Hide description] DESCRIPTION: The prognostic impact of response to induction CT preceding salvage HDCT courses, and prior TXL-chemotherapy for advanced GCT is unknown. This knowledge can inform trial design, stratification and eligibility criteria to HDCT.
[Show abstract][Hide abstract] ABSTRACT: Introduction: HDCT has a recognized indication in the salvage setting of advanced GCT and is steadily utilized
worldwide. While the prognostic impact of response to prior lines of CT (i.e. definition of chemoresistance) is ascertained,
that of response to induction/mobilization CT preceding single or multiple HDCT cycles is unknown. We present the
results of a retrospective study of the EBMT-STWP.
Materials (or patients) and methods: Data have been collected from EBMT registry, including 23 European centers.
Eligibility included adult male patients (pts) with GCT, and treatment with second or further-line HDCT between the years
2002 and 2012. Multivariable logistic model evaluated the association between response to induction CT and line of
HDCT by adjusting for known confounding factors. Multivariable Cox regression analyses were undertaken to evaluate
the association of prespecified factors (site of tumor primary, IGCCCG category, response to induction CT, response to
prior lines [chemosensitive vs chemorefractory], line of HDCT, year of HDCT) with progression-free (PFS) and overall
survival (OS). Cox analyses excluded missing data.
Results: Since 10/2013, 442 pts have been registered, 344 of them were suitable for present analysis. 22 mobilization
regimens were used, including 15 platinum-based CT. HDCT regimens were as follows: 210 (61%) HD-CBDCA-VP16
(CE), 41 (12%) adding ifosfamide (CEI), 32 (9%) CarboPEC, 46 (13%) were taxane-containing, 15 (4%) other various
regimens. HDCT was administered as single (n=142), double (n=95), or multiple (n=106) courses (1 missing). Median
follow up was 30 months (IQR: 15-54).
59 pts (17%) had a progression to induction, 250 (73%) a response (35 [10%] missing or GCSF only). Progression was
significantly associated to the transplant setting (Chi squared test p=0.007).
In the multivariable model for PFS, tumor primary (overall p value=0.039), IGCCCG category (overall p value=0.033), and
progression to induction (HR: 2.02, 95%CI: 1.31-3.12, p=0.001) were significantly prognostic. The latter was also
significantly prognostic for OS (HR: 2.36, 95%CI, 1.44-3.85, p<0.001) together with the transplant setting (overall p
value=0.014). Results for response to induction CT were confirmed in the models that included missing data. The c-index
of the model was 0.62 for PFS and 0.63 for OS.
Conclusion: Progression to induction CT prior to HDCT was independently and significantly associated with shorter PFS
and OS, while response or progression to prior CT lines was not. This information could have important implications to
refine patient eligibility to transplantation and enhance the prognostic risk grouping. These data need external validation.
Disclosure of Interest: None Declared
Keywords: Germ Cell Tumors, high dose chemotherapy, Salvage therapy, Testicular cancer, Transplantation
[Show abstract][Hide abstract] ABSTRACT: The central nervous system (CNS) is an important area of involvement for both high-grade, aggressive primary and secondary lymphomas. Although follicular lymphoma represents a low-grade histology, it may rarely present with CNS involvement. Here, we describe a patient diagnosed with follicular lymphoma who was presented with cerebellar involvement.
Full-text · Article · Sep 2013 · Cancer Research and Treatment
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
Osteosarcoma (OS) is the primary malignant tumor of bone, with an incidence rate of 19% among all cancer types. The vast majority of patients have pulmonary metastases at diagnosis, and about half develop lung disease later, which leads to poor prognosis and increased death rate. It is therefore essential to investigate molecular markers responsible for pulmonary metastasis of osteosarcoma.In this research, a genome wide association study (GWAS) using formalin fixed paraffin embedded (FFPE) samples from lung tissue of 9 patients with pulmonary metastatic OS was performed.
Among 358 associated SNPs, rs6499861, rs10884554 and rs12154602 were found to be associated with metastatic OS most significantly. Moreover, second wave analysis of GWAS results provided the significant genes and pathways associated with metastatic OS, including genes related to metabolic and skeletal development pathways. The present study also demonstrates a feasible approach in using archival FFPE samples for GWAS.
[Show abstract][Hide abstract] ABSTRACT: Background / Purpose:
Formalin fixed paraffin embedded (FFPE) tissues are the most available material for routine diagnostics in pathology laboratories worldwide. They can be used for both microscopic examinations and molecular diagnostic assays after microscopy. Molecular assays, such as PCR and high throughput microarrays, have the potential to be used as routine diagnostic and prognostic tests. Those assays require high quality DNA. However, DNA extracted from FFPE material is problematic due to chemical modifications caused by formalin and continued degradation over time.In this research, FFPE samples from lung tissue of 10 patients with pulmonary metastatic osteosarcoma was used in order to provide a microarray data analysis workflow for application of FFPE-derived DNA samples in reliable copy number and loss of heterozygosity (LOH) predictions.
The present study demonstrates a feasible approach to use archival FFPE samples for the assessment of copy number aberration and LOH.
[Show abstract][Hide abstract] ABSTRACT: Primary (AL type) amyloidosis is the most common form of systemic amyloidosis. The morbidity arises from extracellular deposition of immunoglobulin light chain (LC) fibrils in some organs such as the kidneys, heart and bowel. Primary amyloidosis and multiple myeloma both involve clonal plasma cell proliferation. Distinctive haematological and biochemical laboratory findings may help in early diagnosis. Here we present a 60-year-old man with an exceptional clinical course of an Ig A type multiple myeloma with generalized amyloidosis, causing nephrotic syndrome, complete intestinal colitis and malabsorbtion. Our comprehensive overview of this rare and often fatal disease aims to increase the awareness of AL type amyloidosis. This may facilitate earlier diagnosis and thus allow initiation of prompt and specific therapies, which are indispensable in order to improve disease prognosis.
Full-text · Article · Dec 2011 · Respiratory Medicine CME