Abstract Allogeneic hematopoietic stem cell transplantation (AlloHSCT) is a therapeutic method for the treatment of many malignant and non-malignant hematological diseases but is still associated with significant morbidity and mortality. Disease relapse recurrence and non-relapse mortality (NRM) remain the main causes of failure from AlloHSCT. The identification of the risk factors associated with this continue to be a subject of extensive scientific research. The aim of our study was to identify the prognostic significance of the early lymphocyte recovery (ELR), presented as absolute lymphocyte count (ALC) for the outcome of AlloHSCT.
Primary adenoid cystic carcinoma (PACC) of the skin is a rare tumor with fewer than 70 cases studied in detail in the English literature. This type of tumor shows a prolonged course and a growth pattern usually manifested by multiple local recurrences and has a low potential for distant metastases. The most important modality for primary treatment is surgical resection followed by radiotherapy. We report a woman aged 43 years at the time of diagnosis, who presented with a slow-growing nodule in the right axilla without lymph node enlargement. A wide local excision was performed, and the histology revealed an adenoid cystic carcinoma. During the next 24 years, another four local recurrences were excised (the last one in 2015) and confirmed histologically to be adenoid cystic carcinoma. The patient was given 44 Gy of radiotherapy after the second surgery in 1996. PACC of the skin is a rare tumor with insufficient data concerning the efficacy of the surgical technique and chemotherapy and radiotherapy treatment, even more so in the case of multiple recurrences. After the last recurrence, the patient was offered an active follow-up based on the long tumor-free intervals in the past and because the site of the primary tumor allowed further surgical excisions in future recurrences.
Introduction: One of the most commonly diagnosed types of cancer among men and women is colon cancer. Pathological stage at surgery is one of the most important prognostic features in that type of cancer. The number of lymph nodes found during surgery and the presence of nodal metastases is determining for prognosis and further adjuvant treatment decisions. Unknown nodal status is defined as Nx and the results from an analysis performed by Surveillance, Epidemiology, and End Results Program show that 14% of colon cancer patients are defined as Nx. The prognosis in the Nx group of patients is not known. Theoretically, the overall survival (OS) in Nx subgroup should be equal to OS in N0+N1+N2 patients. The potential benefit of chemotherapy in Nx patients is not known. Methods: A total of 1187 patients with colon cancer that underwent surgery at the Complex Cancer Center Plovdiv from 01.2004 to 12.2011 (734 stage II, 329 stage III and 124 Nx patients) were analyzed retrospectively. Studied data included date of surgery, age, gender, tumor location, lymph node status and tumor differentiation. All stage III patients, Nx patients and 21.9% of stage II patients underwent adjuvant chemotherapy. Survival analysis was performed using Kaplan-Meier method and Cox regression model. Results: For stage II, III and Nx cancer patients, overall survival rates at five years after surgery were 92.4%, 88.3% and 33.9%, respectively. Moreover, the patients with Nx lymph node status were associated with higher risk of death HR- 1.44 (95% CI, 1.028-2.022; p = 0.03). Conclusion: This study shows an unexpected discordance in 5-year overall survival rates between Nx colon cancer patients and patients in stages II plus III. Further investigations are needed to confirm that Nx lymph node status is an independent negative prognostic marker for colon cancer patients.
Background: In allogeneic transplantation the usual approach is to synchronize the conditioning of the patient with stem cell harvesting in order to infuse fresh cell products. The EBMT COVID-19 guidelines recommend cryopreservation of the graft to be considered if there is a concern that the donor is at risk of infection after the patient's conditioning is initiated. Aims: We analyzed if cell viability or hematological recovery is affected in case stem cells are previously frozen. Methods: Results from two groups of patients, each comprising of 16 males and 8 females, were analyzed. HSC from the first group were non-programmed frozen and stored at -80oC in a cryoprotective solution with a final 5% DMSO, 3.6% hydroxyethyl amylopectin (HES, Mw 450 000 Da) and 3% human serum albumin (HSA) concentrations. Platelets and plasma were removed from stem cell harvest prior to the addition of the cryoprotectant. The HSCs from the second group were transplanted without freezing. Fresh cell viability or viability after thawing (trypan blue exclusion test) and hematological recovery (neutrophils and platelets) of patients receiving cryopreserved cells or fresh cells were analyzed. Results: The average viability was 98,67 % (SD ±1,633) for fresh HSCs and 91,63% (SD ±8,021) for cryopreserved cells. The average time for hematological recovery for the neutrophils, was 17,96(SD ±4,601) for fresh cells and 16,46 (SD ± 4,530) for frozen cells. The average time for hematological recovery for the platelets, was 15,25 (SD ± 4,590) for fresh cells and 16,26 (SD ± 6,032) for frozen cells. There was no statistically significant difference between the two groups for hematological recovery. Summary/Conclusion: Use of fresh HSCs is the first choice for allogeneic stem cell transplantation. In cases of pandemics, such as the Covid-19 one, use of cells harvested and frozen prior to initiation of the condioning regimen is preferred. Cryopreservation of HSCs with a cryoprotective solution with low (5%) DMSO concentration and extracellular agents (hydroxyethyl amylopectin and HSA) is safe and well tolerated and gives excellent post thaw viability and post-transplant hematological recovery results.
Background: Dimethylsulfoxide (DMSO) is a major intracellular cryoprotectant, used for cryopreservation of stem cells. It is toxic to both cells and patients at temperatures above 0 o C. Reduction of this effect is achieved by either washing of cells after thawing or by reduction of DMSO during freezing and storage. The latter requires addition of extracellular cryoprotectants to the freezing media. Aims: We assessed the effect of low DMSO concentration and different hematocrits of the frozen cells on cell viability and hematologic recovery in patients, transplanted for multiple myeloma. Methods: Cells were non‐programmed frozen and stored at −80 o C in a cryoprotectant solution achieving final concentrations of 5% DMSO, 3.6% of hydroxyethyl starch (HES, Weight average molecular weight 450 000 Da) and 3% of human serum albumin. The cell concentration in the frozen product for the first 77 patients (84 transplantations) varied between 100x10 6 and 250x10 6 cells/ml. In an attempt to reduce the amount of DMSO infused, for the rest of the patients (n = 172; 192 transplantations) we further decreased the volume of the freezing suspension by removal of the entire plasma. The average age of the transplanted patients was 55 (35 ‐ 71). The cells were bedside thawed at 37 o C water bath. The average cell dose was 2,95x10 6 /kg (1,3 – 9,2x10 6 /kg). Results: Viability of the stem cells following thawing assessed by trypan blue exclusion was 95,34% (70–99). The hematocrit of the frozen cells had no effect on cell viability (94,80%(low) vs 95,52%(high)). The major complaints, if any, during stem cell infusion were coughing and an increase in nausea and vomiting induced by the prior conditioning. The average time for hematological recovery was 11,66 days (between 9 and 19) for the neutrophils, and 12,17 (between 9 and 20) days for the platelets. There was no significant difference in viability and hematologic recovery (11,86 and 12,60 vs 11,59 and 12,02) between patients receiving cells frozen with low or high hematocrit. Summary/Conclusion: Dimethylsulfoxide, despite its cryoprotective properties, is toxic for stem cells at temperatures above zero C and induces many side effects (cardiac, neurologic, respiratory, etc.) in the patients. To reduce those side effects we use lower DMSO concentration, high hematocrit resulting in lower volume of the frozen cell suspension, thus reducing the final quantity of DMSO to be infused to the patients. This does not affect the cell viability or the hematologic recovery of patients after transplantation. Our easily performed method for unprogrammed freezing of stem cells with final DMSO concentration 5% at −80 o C is safe, well tolerated, and provides cryopreservation, which allows high viability and stable cell engraftment, while reducing the undesired side effects of DMSO.
Background: Dimethylsulfoxide (DMSO) is toxic to both cryopreserved cells and patients. We are using a method for freezing at - 80ºC with 5% final DMSO concentration. Aims: In an attempt to further decrease the amount of infused DMSO we tested viability of cells and hematologic recovery of patients following cryopreservation with different degree of cell packing. Methods: We compared two groups of myeloma patients with low and high cryopreserved cells concentration. Cell suspension in the first group of 88 patients contained average 175x106 cells/ml (maximum 250x106 cells/ml) and in the second group of 175 patients the cells were completely packed by total plasma removal (average 391x106 cells/ml and maximum 597 x106 cells/ml) before adding the cryoprotectants resulting in a 60% decrease of the volume to be frozen. Cells were non-programmed frozen and stored at -80ºC in a solution with final concentrations of 5% DMSO, 3.6% hydroxyethyl starch (HES 450 000 mw) and 3% of human serum albumin. Stem cell viability was evaluated by trypan blue exclusion test. Cell dose in the first patient group was 2,62x106/kg (0,8–6,6), while in the second group it was 2,67x106/kg (1,5-6,8). Results: There was no statistically significant difference between the two myeloma patient groups. Viability was 97,0% (85-99) and 96,5 % (70-99) respectively. The neutrophil recovery was on day 11 (9-19) for the first and on day 11 (9-18) for the second group. Platelets recovered after 12 days for the first and the second group. Summary/Conclusion: Dimethylsulfoxide is toxic and induces many side effects following transplant (cardiac, neurologic, respiratory, etc.), which are dose dependent. Reducing them could be achieved by lowering the final DMSO concentration (5%) and by decreasing the volume of the frozen suspension. Our approach does not affect the cellular viability or the hematologic recovery of the patients following transplantation.
e23162 Background: Our study explored the potential relationship between the time estimation and the level of anxiety in cancer patients prior to starting chemotherapy. Methods: Time estimation was assessed in 90 chemonaïve patients with solid tumors by evaluating each subject’s prospective estimation of how fast one minute passed compared to the actual time. The median value (37 sec) of time estimation was used to stratify the patients into two categories of fast and slow time estimation. We used generalized anxiety disorder (GAD-7) as a screening tool for detecting levels of anxiety. Scores ≥10 we considered as clinically significant. Results: Patients with clinically significant levels of anxiety were 23 (25.5%). The pattern of the time estimation distributions significantly changed according to the reported levels of GAD-7 scales. Scores ≥10 correlated with fast time estimation and gender. Patients who scores ≥10 estimated time significantly faster than the rest (27.3±9.2 vs 43.4±17.3; p < 0.001). ROC analysis revealed that at the optimal cutoff value of time estimation, clinically significant levels of anxiety can be discriminated with an AUC = 0.78 (95% CI: 0.68-0.87, p < 0.001) and with a sensitivity of 78.3% and a specificity of 65.2%. Moreover, in a multivariate logistic regression model, fast time estimation was an independent predictor of clinically significant levels of anxiety (OR 7.07; 95% CI 2.2-22.8; p = 0.001). Conclusions: Time estimation is a novel potent indicator for moderate and severe levels of anxiety in cancer patients. This test is an easily performed, time-saving and nonintrusive ultrashort screening tool for clinically significant levels of anxiety.
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