Allogeneic hematopoietic stem cell transplantation from matched related donors for acute myeloid leukemia.

INTRODUCTION: In patients with acute myeloid leukemia (AML), allogeneic hematopoietic stem cell transplantation (HSCT) remains the priority treatment option as the most effective prevention of relapse. When an HLA-matched sibling is available, these transplants are preferred. OBJECTIVES: We stratificated patients according to risk, disease state (an active disease, the 1st or 2nd complete remission ‒ CR1, CR2, which was achieved after the 1st or 2nd induction) and type of graft (from brother or sister). Finally, the overall survival (OS) of patients in individual groups was evaluated. MATERIAL AND METHODS: The retrospective single-center study included 104 transplantations in 97 adult patients with AML who underwent HSCT from matched sibling donor in a period of 10 years between January 2011 and December 2020. RESULTS: 54 patients (55.7%) were alive as of the January 1, 2022. The median OS of the entire group, as well as the cohort with favorable (5y-OS 75.0%) and intermediate prognosis risk (5y‒OS 78.5%) was not reached. We found that patients, who required second induction therapy to achieve CR, had poorer OS after allogeneic HSCT, median 20.7 months (95% CI, 6.5-35.5) than those who achieved CR after first induction, median not reached (95% CI, 63.5‒63.5, p=0.0048). Statistically significant effect on OS shows transplantation in CR2 (HR 6.76, CI 95% 2.19‒20.80, p=0.0009), In addition, this parameter influenced OS more than achieving CR up to the 2nd induction course (HR 2.44, CI 95% 1.17‒5.11; p=0.0180) or entry to transplantation without CR (HR 2.81, CI 95% 1.09‒7.26; p=0.0326). CONCLUSION: The results presented in the work show the high efficiency of HSCT in each risk group. The number of induction therapies required to achieve CR is a good prognostic factor. The gender of a sibling has no impact on OS (Tab. 11, Fig. 7, Ref. 18). Text in PDF www.elis.sk Keywords: acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, overall survival, remission status, donor tender.

Treatment of Adults and Young Adults with Acute Lymphoblastic Leukemia: Real Life Data from Two Centers in Slovakia.

INTRODUCTION: The results of treatment of acute lymphoblastic leukemia (ALL) from the low population countries are missing in the literature. PATIENTS AND METHODS: We retrospectively examined biological characteristics and survival of 90 patients with ALL. RESULTS: At median follow-up 17 months, 52 men and 38 women were eligible for the analysis with median age 43 years (18-74). As for the risk stratification, 25.6% of patients were in standard risk, 46.7% in high risk and 27.8% in very high-risk group. Complete remission achieved 88.9% of patients. We observed 5.6% of induction deaths and 4.5% of resistant disease. 47.8% of the patients underwent allogeneic stem cell transplantation (alloSCT), 59% in the young adults (YA; < 40 years) and 40% in adult group (≥ 40 years). We noticed 32.6% relapses overall with median survival of relapsed patients 3.9 months. YA patients had longer survival than adults: 3-year overall survival (OS) 65.0% vs 30.2%; (HR = 0.36; 95% CI 0.2-0.64; P = .001) and event free survival (EFS) 51.5% vs 21.9%; (HR = 0.45; 95% CI 0.26-0.78; P = .005). There was significant difference in 3-year EFS between risk groups in YA patients 90.9%, 48.0%, 11.4%; (P = .001). OS after alloSCT individually for the YA was 62.6% and for adults 39.1%, hazard ratio (HR) = 0.49 (95% CI 0.20-1.21); (P = .095). We observed 14% early deaths, 25.6% late deaths and 3 relapses (7%) after allogeneic stem cell transplantation. CONCLUSIONS: Our data proved that even in a low population country similar result can be achieved as in larger ones while using well designed adapted protocols from leukemic study groups.

Plasma thiobarbituric acid reactive substances predicts survival in chemotherapy naïve patients with metastatic urothelial carcinoma.

Oxidative stress plays a significant role in development and progression of cancer, including urothelial carcinomas. TBARS (Thiobarbituric acid reactive substances) represents a marker of oxidative stress increased in various diseases. In this prospective study, we tested the hypothesis of plasma TBARS concentration and correlation with survival in chemotherapy naïve MUC (metastatic urothelial carcinoma) patients. Most of subjects (N = 65) were treated with gemcitabine and cisplatin (GC) chemotherapy. Performance status ECOG ≥2 had 11 patients, visceral metastases were present in 43. Based upon the mean of plasma TBARS, subjects were dichotomized into low and high groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared by log-rank test. At median follow-up of 9.6 months, 65 patients experienced progression and 64 died. Subjects with low TBARS had significantly better PFS (HR 0.51) and OS (HR 0.44) opposed to high TBARS. Patients with low TBARS had significantly higher rate of neutropenia G4 and less liver involvement. High TBARS correlated with BMI above 30 kg/m2. Performance status and plasma TBARS were proven to be independent predictors of PFS and OS. In this study, high TBARS in MUC patients were associated with poor survival, likely due to more aggressive disease activity as reflected in increased liver involvement. Therefore, this biomarker could be used in clinical practice for early identification of patients with worse prognosis, better patient stratification, and treatment decision making.

A unique clinical presentation of de novo acute promyelocytic leukemia as a myeloid sarcoma of the breast.

Myeloid sarcoma is a rare presentation of acute leukemia as a solid tumor at various extramedullary sites. It may present concurrently, before or after the onset of systemic bone marrow leukemia. Unusual clinical localization may lead to misdiagnosis, or delayed diagnosis and treatment. We describe the first case, to our knowledge, of de novo myeloid sarcoma of the breast confirmed as acute promyelocytic leukemia. Immunohistochemical analysis, flow cytometry, fluorescent in situ hybridization analysis and molecular analysis using RQ-PCR of tissue samples should be routine in determining the correct diagnosis in this setting.

Long-Term Cognitive Functioning in Testicular Germ-Cell Tumor Survivors.

BACKGROUND: Treatment for cancer may lead to development of cognitive difficulties in cancer survivors. This study aimed to evaluate long-term cognitive functioning (CogF) in germ-cell tumor (GCT) survivors. SUBJECTS, MATERIALS, AND METHODS: GCT survivors (n = 155) from the National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function at a median of 10 years of follow-up (range: 5-32). The study group consisted of survivors receiving a cisplatin-based chemotherapy, radiotherapy to the retroperitoneal lymph nodes, or both, whereas the control group included survivors treated with orchiectomy only. RESULTS: Of the total survivors, 138 received treatment beyond orchiectomy and 17 controls had orchiectomy alone. Any treatment resulted in significantly greater cognitive difficulties on the overall cognitive function score. Treatment with radiotherapy was associated with cognitive declines in overall cognitive functioning and in subscales for perceived cognitive impairment and cognitive impairment perceived by others (both p < .05). The burden of chemotherapy plus radiotherapy or radiotherapy versus controls resulted in the impairment in all cognitive functioning domains (all p < .05). Overall long-term cognitive impairment was independent of age in the multivariable analysis. CONCLUSION: This prospective study shows that GCT survivors suffer from a long-term CogF impairment. These results may help guide clinicians' decisions in treatment and follow-up of GCTs. IMPLICATIONS FOR PRACTICE: In this study, long-term survivors of germ-cell tumors have reported cognitive impairment after curative treatment with radiotherapy and chemotherapy compared with controls who had treatment with orchiectomy only. These data provide an argument against the use of adjuvant radiotherapy for stage I seminoma. Unnecessary overtreatment with chemotherapy and additional radiotherapy after chemotherapy should be avoided.

Plasma Cytokines Correlated With Disease Characteristics, Progression-Free Survival, and Overall Survival in Testicular Germ-Cell Tumor Patients.

BACKGROUND: Cytokines are the communicators of immune system and are involved in all immune responses. The aim of this study was to assess the correlation among plasma cytokines, patient and tumor characteristics, and clinical outcome in chemonaive testicular germ-cell tumor (TGCT) patients. PATIENTS AND METHODS: This study included 92 metastatic chemotherapy-naive TGCT patients treated with platinum-based chemotherapy from July 2010 to March 2014. Plasma was isolated before first administration of chemotherapy, and the concentration of 51 plasma cytokines were analyzed using multiplex bead arrays. RESULTS: At a median follow-up of 33.2 months (range, 0.1-54.8 months), 10.9% of patients experienced disease progression, and 7.6% died. Several cytokines were associated with different baseline clinicopathologic features. Elevated plasma levels of interferon (IFN)-α2, interleukin (IL)-2Rα, IL-16, hepatocyte growth factor (HGF), and monocyte chemotactic protein (MCP)-3 were significantly associated with worse progression-free survival and overall survival (OS). Moreover, elevated levels of stem-cell growth factor (SCGF)-ß were also associated with worse OS. Patients with elevated levels of all 6 cytokines experienced significantly worse outcomes compared to patients who had fewer than 6 cytokines elevated (hazard ratio = 12.06; 95% confidence interval, 7.39-19.49; P = .002 for progression-free survival, and hazard ratio = 39.65; 95% confidence interval, 25.03-62.18; P < .00001 for OS, respectively). Results were independent of International Germ Cell Cancer Collaborative Group criteria. CONCLUSION: We found a correlation among progression free-survival, OS, and circulating cytokines in TGCT. This suggests the existence an association between plasma cytokines and baseline clinicopathologic features in TGCT. Plasma cytokines could be used for identification of high-risk patients who are candidates for new therapeutic approaches.

The prognostic value of DNA damage level in peripheral blood lymphocytes of chemotherapy-naïve patients with germ cell cancer.

Germ cell tumors (GCTs) are extraordinarily sensitive to cisplatin (CDDP)-based chemotherapy. DNA damage represents one of the most important factors contributing to toxic effects of CDDP-based chemotherapy. This study was aimed to evaluate the prognostic value of DNA damage level in peripheral blood lymphocytes (PBLs) from chemo-naïve GCT patients. PBLs isolated from 59 chemotherapy-naïve GCT patients were included into this prospective study. DNA damage levels in PBLs were evaluated by the Comet assay and scored as percentage tail DNA by the Metafer-MetaCyte analyzing software. The mean ± SEM (standard error of the mean) of endogenous DNA damage level was 5.25 ± 0.64. Patients with DNA damage levels lower than mean had significantly better progression free survival (hazard ratio [HR] = 0.19, 95% CI (0.04 - 0.96), P = 0.01) and overall survival (HR = 0.00, 95% CI (0.00 - 0.0), P < 0.001) compared to patients with DNA damage levels higher than mean. Moreover, there was significant correlation between the DNA damage level and presence of mediastinal lymph nodes metastases, IGCCCG (International Germ Cell Cancer Collaborative Group) risk group, and serum tumor markers level. These data suggest that DNA damage levels in PBLs of GCT patients may serve as an important prognostic marker early identifying patients with poor outcome.

Matrix metalloproteinase 1 and circulating tumor cells in early breast cancer.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved in cancer invasion and metastasis. Circulating tumor cells (CTCs) play role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. The aim of this study was to assess correlation between CTCs and tumor MMP1 in BC. METHODS: Study included 149 primary BC patients treated by surgery from March 2012 to March 2013. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep(TM) selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, ZEB1) and epithelial (CK19) gene transcripts by qRT-PCR. Patient samples with higher epithelial and/or mesenchymal gene transcripts than those of healthy donors (n = 60) were considered as CTC positive. Expression of MMP1 in surgical specimens was evaluated by immunohistochemistry. RESULTS: CTCs were detected in 24.2% patients. CTCs exhibiting only epithelial markers were present in 8.7% patients, whereas CTCs with epithelial-mesenchymal transition (EMT) markers (CTC_EMT) were observed in 13.4% of patients and CTCs co-expressing both markers were detected in 2.0% patients. Patients with CTC_EMT in peripheral blood had significantly increased expression of MMP1 in tumor cells (p = 0.02) and tumor associated stroma (p = 0.05) than those of patients without CTC_EMT. In multivariate analysis, CTC_EMT and tumor grade were independently associated with MMP1 expression in cancer cells, while CTC_EMT and Ki67 were independently associated with MMP1 expression in cancer associated stroma. CONCLUSION: Our data suggest link between MMP1 and CTCs with EMT phenotype and support role of MMPs and EMT in tumor dissemination.