Multiple Cycles Of Chemotherapy Research Articles

Moxibustion combined with guasha therapy for recurrent neutropenia following multiple cycles of chemotherapy of ovarian cancer: a case report.

Neutropenia, a common side effect of chemotherapy for ovarian cancer, was observed in a 47-year-old female patient undergoing a six-cycle chemotherapy regimen. She experienced recurrent neutropenia and leukopenia but refused granulocyte colony-stimulating factor (G-CSF) due to severe bone pain and high costs. Moxibustion combined with guasha therapy (MGT) was administered each time neutropenia occurred. The treatment involved guasha therapy on the bladder meridian (BL) and the governor vessel (GV), followed by moxibustion at Zhongwan (CV 12), Guanyuan (CV 4), and Shenzhu (GV 12) points over 2-3 days. This approach led to the recovery of neutrophil and leukocyte counts, enabling the patient to complete six chemotherapy cycles without G-CSF. These findings suggest that MGT may enhance neutrophil and leukocyte counts in patients with chemotherapy-induced myelosuppression, presenting a potential alternative for those intolerant to G-CSF. However, further high-quality research is needed to confirm its efficacy.

Botyroid Rhabdomyosarcoma of the Vagina in A Two-month-old Girl

Botyroid rhabdomyosarcoma is the most common malignant mesencymal tumor of the vagina in children and infants. It is a malignant tumor that arises from immature skeletal muscle cells (i.e., rhabdomyoblasts) lining the walls of hollow organs, including the vagina, bladder, and biliary tract. This cancer most commonly affects children under the age of 4, although it can sometimes present in older individuals. Botyroid sarcoma is usually found in the vagina during infancy and early childhood, in the cervix during reproductive years, and in the corpus uteri during postmenapausal years. Treatment is combination of surgery with adjuvants chemotherapy and radiotherapy. We report a case of two-month-old girl presented with a history of vaginal bleeding and a mass protruding from vagina. Diffusion Magnetic Resonance Imaging (MRI) showed an approximately 6 cm mass in rectovaginal septum. Excisional biopsy from the vagina confirmed the diagnosis of botyroid rhabdomyosarcoma. After biopsy the patient received multiple cycles of chemotherapy. The patient is disease-free on remission at this time.

Optimized rat models better mimic patients with irinotecan-induced severe diarrhea

Irinotecan-induced severe diarrhea (IISD) not only limits irinotecan’s application but also significantly affects patients’ quality of life. However, existing animal models often inadequately represent the dynamics of IISD development, progression, and resolution across multiple chemotherapy cycles, yielding non-reproducible and highly variable response with limited clinical translation. Our studies aim to establish a reproducible and validated IISD model that better mimics the pathophysiology progression observed in patients, enhancing translational potential. We investigated the impact of dosing regimens (including different dose, infusion time, and two cycles of irinotecan administration), sex, age, tumor-bearing conditions, and irinotecan formulation on the IISD incidence and severity in mice and rats. Lastly, we investigated above factors’ impact on pharmacokinetics of irinotecan, intestinal injury, and carboxylesterase activities. In summary, we successfully established a standard model establishment procedure for an optimized IISD model with highly reproducible severe diarrhea incidence rate (100%) and a low mortality rate (11%) in F344 rats. Additionally, the rats tolerated at least two cycles of irinotecan chemotherapy treatment. In contrast, the mouse model exhibited suboptimal IISD incidence rates (60%) and an extremely high mortality rate (100%). Notably, dosing regimen, age and tumor-bearing conditions of animals emerged as critical factors in IISD model establishment. In conclusion, our rat IISD model proves superior in mimicking pathophysiology progression and characteristics of IISD in patients, which stands as an effective tool for mechanism and efficacy studies in future chemotherapy-induced gut toxicity research.

Abstract B023: Paracrine enhancement of tumor cell proliferation provides indirect stroma-mediated chemoresistance via acceleration of tumor recovery between chemotherapy cycles

Abstract The ability of tumors to survive therapy reflects both cell-intrinsic and microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stroma/tumor ratio correlates with poor survival. In many contexts, this correlation can be explained by the direct reduction of therapy sensitivity by stroma-produced paracrine factors. We sought to explore whether this direct effect contributes to the link between stroma and poor responses to chemotherapies. Our in vitro studies with panels of TNBC cell line models and stromal isolates failed to detect a direct modulation of chemoresistance. At the same time, consistent with prior studies, we observed treatment-independent enhancement of tumor cell proliferation by fibroblast-produced secreted factors. Using spatial statistics analyses, we found that proximity to stroma is often associated with enhanced tumor cell proliferation in vivo. Based on these observations, we hypothesized an indirect link between stroma and chemoresistance, where stroma-augmented proliferation potentiates the recovery of residual tumors between chemotherapy cycles. To evaluate the feasibility of this hypothesis, we developed a spatial agent-based model of stroma impact on proliferation/death dynamics. The model was quantitatively parameterized using inferences from histological analyses and experimental studies. We found that the observed enhancement of tumor cell proliferation within stroma-proximal niches can enable tumors to avoid elimination over multiple chemotherapy cycles. Therefore, our study supports the existence of a novel, indirect mechanism of environment-mediated chemoresistance that might contribute to the negative correlation between stromal content and poor therapy outcomes. Citation Format: Daria Miroshnychenko, Tatiana Miti, Pragya Kumar, Anna Miller, Mark Laurie, Nathalia Giraldo, Marilyn M. Bui, Philipp M. Altrock, David Basanta, Anriy Marusyk. Paracrine enhancement of tumor cell proliferation provides indirect stroma-mediated chemoresistance via acceleration of tumor recovery between chemotherapy cycles [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B023.

Prevalence of acute myeloid leukemia and its associated risk factors at a tertiary care center: a retrospective cross-sectional study.

Acute myeloid leukemia (AML) is a common malignant disorder of the bone marrow, accounting for 23.1% of total leukemia cases globally in 2017. This study aimed to know the prevalence of AML in a tertiary hospital center in Nepal and assess the associated etiological factors in the causation of AML. A hospital-based retrospective cross-sectional study was conducted among patients with acute leukemia admitted to a tertiary care center in Kathmandu from 1 April 2021 to 30 April 2022. Three hundred and ten participants with acute leukemia were selected via a convenience sampling technique. The data were entered into Microsoft Excel 365 and then analyzed using Statistical Packages for Social Sciences version 22.0. One hundred and forty five (46.7%) out of 310 acute leukemia patients had AML. Most of the cases were male (104, 71.7%) and aged 40-49 years (36, 24.8%). The most common signs and symptoms were pallor (115, 79.3%), fever (n=92, 63.4%), and lethargy/weakness (78, 53.8%). Ninety one (62.8%) patients underwent multiple cycles of chemotherapy while 51 (35.2%) had supportive care only, and 3 (2.1%) went bone marrow transplants. The prevalence of AML was higher as compared to AML in other studies done in a similar setting. Early diagnosis and treatment are key to a good prognosis and cure in most cases.

Extended pleurectomy/decortication and hyperthermic intraoperative intrapleural cisplatin perfusion for malignant pleural mesothelioma

ObjectiveTo evaluate the efficacy of multimodality treatment including extended pleurectomy/decortication (P/D) and hyperthermic intraoperative chemotherapy (HIOC) with cisplatin for malignant pleural mesothelioma (MPM), we investigated the pharmacokinetics of platinum, adverse events after HIOC, and survival outcome. MethodsFifty-three patients with pathologically diagnosed MPM (cT1-3N0-1M0, excluding sarcomatoid) underwent an extended P/D and HIOC (cisplatin 80 mg/m2 in saline 2 L, 42°C, 60 minutes) since 2011. The protocol includes postoperative 4 cycles of cisplatin and pemetrexed. Platinum concentrations in the perfusate (before and after) and the serum (1, 2, 4, 8, 24, 48, 72 hours after perfusion) were measured in 10 patients. Mortality and morbidity, especially adverse events of renal function, were investigated, and survival and affecting factors were examined. ResultsAll patients obtained macroscopic complete resection and pathologic staging revealed as follows: T1/2/3/4: 12/8/23/10, N0/1: 36/17, stage 1A/1B-3A/3B: 12/31/10, respectively. Platinum concentrations in the perfusate indicated that 28% of the dose remained in the pleural cavity, and the maximum concentration in the serum was 0.91 μg/mL. Six patients (11%) showed elevated max-creatinine (>2 mg/dL) postoperatively. Two patients (4%) received renal-replacement therapy, and one was weaned before discharge. There was no 30-day mortality and one in-hospital death (1.9%). Forty-six patients (87%) received multiple cycles of perioperative systemic chemotherapy. Median overall survival (OS) and disease-free survival (DFS) were 52.4 months and 18.7 months. Patents with stage 1A demonstrated a 5-year OS of 67.3% and a median DFS of 67.1 months, and patients with stage 1B-3A demonstrated a 5-year OS of 50.1% and a median DFS of 20.4 months. Univariate analysis showed histological subtype, p-T, p-stage, and multimodality treatment as significant factors affecting OS. Multivariate analysis revealed histology, p-stage, and multimodality as independent. ConclusionsExtended P/D and HIOC with cisplatin for MPM is acceptable with limited acute kidney injury. This multimodality protocol provides promising favorable survival for stage 1A-3A disease.

Radioimmunotherapy of Non-Hodgkin B-cell Lymphoma: An update.

Systemic radioimmunotherapy (RIT) is arguably the most effective and least toxic anticancer treatment for non-Hodgkin lymphoma (NHL). In treatment-naïve patients with indolent NHL, the efficacy of a single injection of RIT compares with that of multiple cycles of combination chemotherapy. However, 20 years following the approval of the first CD20-targeting radioimmunoconjugates 90Y-Ibritumomab-tiuxetan (Zevalin) and 131I-tositumomab (Bexxar), the number of patients referred for RIT in western countries has dramatically decreased. Notwithstanding this, the development of RIT has continued. Therapeutic targets other than CD20 have been identified, new vector molecules have been produced allowing for faster delivery of RIT to the target, and innovative radionuclides with favorable physical characteristics such as alpha emitters have been more widely available. In this article, we reviewed the current status of RIT in NHL, with particular focus on recent clinical and preclinical developments.

Autologous myocutaneous flap implantation for chronic refractory chest wall sinus with infection: a case report

BackgroundChest wall sinus with infection is a refractory disease caused by a variety of susceptible factors, and the treatment is still challenging. For clinically complex cases, although there are various surgical methods to choose from, it is still very difficult to achieve clinical cure, especially for patients with older age and many underlying diseases. Complete resection of chest wall sinus and application of repair and reconstruction technology may bring hope to refractory cases.Case presentationHerein, we report a case of a 67 year-old woman who had undergone breast cancer surgery and a history of multiple cycles of radiotherapy and chemotherapy. One year ago, she had a fistula in the left chest wall with yellow purulent fluid. After admission to our hospital, chest computed tomography (CT) showed the formation of the left chest wall sinus, accompanied by high-density images of the left clavicle, part of the ribs and part of the sternu. According to the patient's symptoms, signs and imaging examination, we preliminarily diagnosed the patient as chest wall sinus with infection and chronic osteomyelitis. Therefore, in the first-stage operation, the patient underwent left chest wall sinus resection, left partial rib resection, left partial clavicular resection and left partial sternal resection, After surgery, the wound surface was changed with gauze dressing with sensitive antibiotic solution every day until the wound surface was clean and new granulation was formed. In the second-stage operation, the wound surface was appropriately expanded, and the pedicled latissimus dorsi myocutaneous flap was transferred to the chest wall defect. Finally, the skin paddle was sutured without tension to the normal skin around the chest, and two drainage tubes were placed. Anti-infection, anti-spasm, anti-coagulation and other treatments were given after operation, and the survival of myocutaneous flap, wound healing and sinus disappearance were observed.ConclusionThe application of pedicled latissimus dorsi myocutaneous flap in the treatment of intractable chronic chest wall sinus is an effective method. It does not change the shape of the thorax. The clinical effect is satisfactory in the near and medium term, which is worthy of clinical promotion.

5P Physiologically relevant treatment models to investigate epigenetic mechanisms driving platinum resistance in ovarian high grade serous carcinoma

The prognosis for patients with platinum-resistant ovarian High Grade Serous Carcinoma (HGSC) remains poor. BriTROC-1 data indicate that genomic alterations alone cannot explain acquired platinum resistance. We investigate epigenetic changes that may drive platinum resistance in HGSC. Using in an in vitro two-dimensional model, we recreated multiple cycles of chemotherapy. We utilised both established cell lines and primary cultures derived from HGSC ascites. Following cell characterisation (p53, PAX8 IHC), carboplatin sensitivity was assessed (sulforhodamine B assay). Cells were then pulsed with four cycles of carboplatin (50μM for 6 hours) with a week of recovery between each cycle. Methylation (Illumina 850k array), transcriptomic (RNAseq) and chromatin accessibility (ATACseq) assays were performed. Cells were also imaged using Stochastic Optical Reconstruction Microscopy. Firstly, we focused on RNAseq analysis to evaluate genes (and related biological processes) that are consistently enriched following carboplatin cycles and the unique genes that are conversely enriched at cycle level. We attempted to identify uniformly up-/down-regulated pathways across the different cultures. These data were compared with the same results obtained from the OvCar4, an established HGSC cell line and IVR01, an in-vivo resistant OvCar4 derivative. The ATACseq and methylation analyses are still ongoing, aiming to identify possible concordant changes in the chromatin accessibility and the methylation patterns that will allow us to clarify the changes observed in transcriptomic. The preliminary data obtained from the RNAseq analysis show that the highest number of enriched genes seems to occur after the first Carboplatin cycle, with a lower number of progressively enriched genes across all other ones. No constant biological processes were identified for the moment, across the different primary cell cultures. Further comparisons will be certainly needed. Understanding the epigenetic landscape of HGSC using physiologically relevant models will allow us to identify possible therapeutic targets that could eventually prevent platinum resistance.

Acute Kidney Injury after Multiple Cycles of Cisplatin Chemotherapy: A Nomogram for Risk Assessment

Introduction: Acute kidney injury (AKI) caused by cisplatin is common and has a higher incidence of multiple use, resulting in a poor short- and long-term prognosis for patients. There is currently no good premedication AKI risk assessment tool. The aim of this study was to establish an AKI risk assessment nomogram for patients with multiple cisplatin applications. Methods: This study was a retrospective analysis of patients who were treated with non-first-time cisplatin chemotherapy regimen at Changzhou Second People’s Hospital affiliated to Nanjing Medical University from January 2016 to January 2022. All data from the development group were used to screen the impact factors of AKI via univariate and multivariate analyses. A nomogram was developed based on these impact factors and verified with verification group. The area under the curve (AUC) of receiver operating characteristic (ROC) curve, calibration curves, and decision curve analyses (DCAs) were used to evaluate the nomogram. Results: Among the 256 patients enrolled in 450 cycles of chemotherapy, 282 were in the development cohort (97 AKI), and 168 were in the validation cohort (61 AKI). Multivariate logistic regression revealed that age, hypertension, diabetes, serum cystatin C (sCysC), urinary kidney injury molecule-1 (uKim1), and a single dose of cisplatin were independently associated with AKI. The results showed that our model yielded satisfied diagnostic performance with an AUC value of 0.887 and 0.906 using the development group and on verification group. The calibration plots and DCA showed the superior clinical applicability of the nomogram. These results were verified in the validation cohort. Conclusion: A nomogram combining functional (sCysC) and tubular (uKim1) injury biomarkers with conventional clinical factors might assess the risk of AKI after multiple cycles of cisplatin chemotherapy.

Spontaneous Regression of Lung Carcinoma: An Essential Review

Lung cancer is the second leading cause of cancer in both males and females in the United States, as it has been estimated that 200,000 new cases will appear in males and females in the U.S, accounting for 14% of new cancers. Lung cancer accounts for 25% of cancer fatalities and has the lowest survival rates. Cancer Spontaneous Regression (SR) is defined as either partial or complete, and temporary or permanent, disappearance without appropriate treatment for the disease, and is a very rare phenomenon of unknown mechanism. The exact incidence of cancer SR is unknown. 176 cases of cancer SR have been reported from 1900 to 1964 with an assessed incidence of 1/ 60,000-100,000 cancer patients, whereas another research found total 15 cases from 1954 to 1997, and more recently 741 cases of SR of malignant diseases in the literature between 1900 and 1987 have been recorded. SR cases concerned several types of malignancies such as lymphoma, leukemia, retinoblastoma, neuroblastoma, melanoma, choriocarcinoma, renal, bladder, and breast cancer, and represented 69% of all SR cases, whereas lung cancer SR only observed in 2.6% of all patients with SR. A few cases reported that SR is an extremely rare biological event in primary lung cancer, and in particular, SR of non-small cell lung cancer (NSCLC) has been scarcely reported. The SR incidence of advanced NSCLC is relatively low, as approximately 20 cases were recorded from 1950 to 2004, and no more than 15 new cases have been reported in the last 12 years. 10 articles describing NSCLC SR between 1997and 2018 have also been observed. Currently, 17 well-documented case reports of lung cancer SR concerning NSCLC and small cell lung cancer (SCLC) have been described. A total of 25 cases of lung cancer were identified between 1987and 2020. Squamous cell carcinoma (SQCLC) accounted for 10 cases, followed by NSCLC not otherwise defined and adenocarcinomas. The pathogenesis of SR cancer is poorly understood, however recent investigations revealed the role of immunological mechanisms, consequently indicating possible therapy options by specific immunotherapy in the future. It has also been supposed that there may be an immunological association between the stimulus of the biopsies and the SR. Recent researches have shown that immunological reaction can be initiated by trauma to an anatomic location. In some cases the tumor SR became evident only after the tissue biopsy, observation that leads to the option that immune response to the surgical procedure seems to be a plausible contributor to the SR. Para-neoplastic sensorimotor neuropathy (PNS) has been suggested as a mechanism of SCLC and NSCLC SR. Specific anti-neuronal auto-antibodies, anti-Hu antibodies, react both to the tumor and nervous system, in patients with sensorimotor neuropathy, and this inflammatory response has been associated with the antitumor immune response. Many cases of SCLC SR have been escorted by neurological symptoms, but no neurological abnormalities were observed. However, the real association between PNS, Hu-antibody and SR of lung cancer still needs to be clarified by further evidence. It has also been recorded that bronchoscopy contributed to SR of lung cancers. Diverse case reports have recorded patients with advanced, poorly differentiated NSCLC (highly expressing programmed death ligand-1 [PD-L1]) that progressed despite multiple cycles of chemotherapy but then spontaneously remitted, patients with lung squamous cell carcinoma who experienced SR following biopsy without other therapeutic intervention, and patients with lung adenocarcinoma that spontaneously remitted. Almost all case reports described SR of an untreated lung cancer and were diagnosed and histologically confirmed.

Impact of neoadjuvant chemotherapy duration on the survival of patients with advanced stage high-grade serous or endometrioid ovarian carcinoma (359)

Impact of neoadjuvant chemotherapy duration on the survival of patients with advanced stage high-grade serous or endometrioid ovarian carcinoma (359)

PEG-rhG-CSF for prophylaxis of neutropenia after chemotherapy in patients with non-small cell lung cancer: A multicenter, prospective, randomized study.

BackgroundTo evaluate the efficacy and safety of pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF) in preventing neutropenia during multiple cycles of chemotherapy in patients with non–small cell lung cancer (NSCLC).MethodIn a multicenter, prospective, randomized trial, patients with NSCLC were randomly assigned in a 2:1 ratio to treatment group (PEG‐rhG‐CSF as primary prophylactic therapy) or control group. Patients in the control group were administered rhG‐CSF when white blood cell count was <2.0 × 109/L or absolute neutrophil count <1.0 × 109/L. The primary endpoint was the incidence of grade 3/4 neutropenia. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia in each cycle, the incidence of febrile neutropenia (FN), delay rate of chemotherapy, prolonged time of chemotherapy, and safety.ResultsBetween January 2019 and July 2021, 130 patients were enrolled (treatment group: n = 87, control group: n = 43). The incidence of grade 3/4 neutropenia in the treatment group was significantly lower than that in the control group (1.15% vs. 11.63%, p < 0.05). The mean duration of grade 3/4 neutropenia for the treatment and control group was 2.00 and 3.75 days, respectively. There were no statistical differences in the incidence of FN, delay rate of chemotherapy, prolonged time of chemotherapy, and antibiotic use between the two groups (all p > 0.05). Adverse events were reported in 47.13% of patients in the treatment group and 48.84% patients in the control group.ConclusionsPrimary prophylactic treatment with PEG‐rhG‐CSF could reduce the incidence of neutropenia in patients with NSCLC during multiple cycles of chemotherapy, with acceptable safety and tolerability.

MT17 Assessment of Device Failures and Medication Errors with the Pegfilgrastim on-Body Injector in the US and EU

The pegfilgrastim on-body injector (OBI) facilitates the time-released administration of pegfilgrastim the day after chemotherapy, as clinically recommended for the prevention of febrile neutropenia. As patients undergo multiple chemotherapy cycles and receive a new OBI device each cycle, estimation of device failure rates should be normalized to the number of devices used. Past studies reported OBI failure rates up to 6.9%. Error rates are overestimated when they are based on per patient rather than per device or chemotherapy cycle.

Effect of avatrombopag in the management of severe and refractory chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors

Chemotherapy-induced thrombocytopenia (CIT) is a common complication in cancer patients, especially after multiple cycles of chemotherapy, which leads to the delayed treatment or reduced dosage. The treatment of CIT is limited for refractory and severe cases. Herein we reported a single-center study of avatrombopag, a type of thrombopoietin receptor agonist (TPO-RA), for the treatment of severe and refractory (S/R) CIT who failed from multi-line treatments. A total of 13 cancer patients with S/R CIT were enrolled at the First Affiliated Hospital of Zhejiang Chinese Medical University from September 2020 to February 2021. All the patients were administered oral avatrombopag at an initial dose of 60 mg/day, which could be decreased as needed, over a period of 8 weeks. Eight (8/13, 61.5%) patients responded to avatrombopag (with a platelet count ≥50 × 109/L and transfusion independent), with a median response time of 27.5 (11–50) days, and the median cumulative day of platelet response was 79 (20–167). Ten of 13 patients (76.9%) no longer required platelet transfusion at the study endpoint. The predictor of response was the level of hemoglobin (HB) at study entry, patients with an HB over 90 g/L achieved a response rate of 88.9%. In addition, platelet count showed 87.5% sensitivity and 100% specificity to predict the treatment response at a cutoff value of 25.5× 109/L at the end of the third week management. No drug-related side effects were noticed during administration. Our study showed that avatrombopag could be a novel and effective drug for the treatment of severe and refractory CIT, especially for those with hemoglobin above 90 g/L. This study was registered at chictr.org.cn as # ChiCTR2100050646.

High-grade esophageal neuroendocrine neoplasm with waxing and waning disease course and differential response to chemotherapy: Dual tracer positron emission tomography-computed tomography (18F-flurodeoxyglucose and 68Ga-DOTATATE) features and disease monitoring with functional molecular imaging

Esophageal neuroendocrine neoplasms (NENs) are uncommon type of esophageal malignancies. We describe the clinical course and molecular imaging features of the relatively rare esophageal malignancy (an aggressive poorly differentiated NEN) that was widely metastatic at the initial presentation. The patient underwent multiple cycles of chemotherapeutic regimens, employing cisplatin-etoposide and nanopaclitaxel-carboplatin and later on rechallenge with cisplatin-etoposide. There was observation of fluctuating disease course and differential characteristics of tumor lesions in terms of treatment response and recurrences with multiple cycles of chemotherapy. In view of the histopathology of high Mib-1 labeling index and dual tracer positron emission tomography-computed tomography (PET-CT) (flurodeoxyglucose [FDG] and 68Ga-DOTATATE) features, the patient was not a suitable candidate for 177Lu-DOTATATE PRRT and FDG PET-CT was the preferred imaging modality for both treatment response assessment and disease monitoring in this patient. The varying response among metastatic lesions in the same individual (with one lesion showing partial response and the other one demonstrating disease progression) was an additional noteworthy feature of the case.

Celecoxib and Myrtol: A Novel Therapy for Recurrent Appendiceal Mucinous Neoplasms With Extensive Peritoneal Dissemination.

Unresectable appendiceal mucinous neoplasms (AMNs) with extensive peritoneal dissemination cause significant morbidity and have limited treatment options. We evaluated a novel combination of Celecoxib and Myrtol in treating such AMNs. Patients with recurrent AMNs with extensive peritoneal disease treated with a daily regimen of 200 mg Celecoxib and 1200 mg Myrtol Standardized were included. Progression-free survival (PFS) and overall survival (OS) were calculated, and carcinoembryonic antigen (CEA) trends were compared pretreatment and post-treatment in terms of percentage change. Thirteen patients with extensive, recurrent disease (median peritoneal carcinomatosis index of 36) were included between 2017 and 2020. The median age was 63 years (interquartile range: 55 to 67) and 7 (54%) were male. A total of 85% had undergone prior cytoreductive surgery while 15% underwent cytoreductive surgery >2 times. 54% had received multiple cycles of systemic chemotherapy before starting Celecoxib-Myrtol. After a median follow-up of 8 months, median PFS and OS were 16 months (interquartile range: 5 to 17) and 27 months, respectively. Nine (69.2%) showed improvement in CEA values 3 months after treatment compared with 3-month pretreatment CEA trends. None had adverse events attributable to Celecoxib-Myrtol. Our feasibility study suggests that a regimen of Celecoxib-Myrtol is well tolerated and may prolong PFS and OS in patients with recurrent AMNs with peritoneal spread.

Hematopoietic stem cell mobilization strategies to support high-dose chemotherapy: A focus on relapsed/refractory germ cell tumors.

High-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation has been explored and has played an important role in the management of patients with high-risk germ cell tumors (GCTs) who failed to be cured by conventional chemotherapy. Hematopoietic stem cells (HSCs) collected from the peripheral blood, after appropriate pharmacologic mobilization, have largely replaced bone marrow as the principal source of HSCs in transplants. As it is currently common practice to perform tandem or multiple sequential cycles of HDCT, it is anticipated that collection of large numbers of HSCs from the peripheral blood is a prerequisite for the success of the procedure. Moreover, the CD34+ cell dose/kg of body weight infused after HDCT has proven to be a major determinant of hematopoietic engraftment, with patients who receive > 2 × 106 CD34+ cells/kg having consistent, rapid, and sustained hematopoietic recovery. However, many patients with relapsed/refractory GCTs have been exposed to multiple cycles of myelosuppressive chemotherapy, which compromises the efficacy of HSC mobilization with granulocyte colony-stimulating factor with or without chemotherapy. Therefore, alternative strategies that use novel agents in combination with traditional mobilizing regimens are required. Herein, after an overview of the mechanisms of HSCs mobilization, we review the existing literature regarding studies reporting various HSC mobilization approaches in patients with relapsed/refractory GCTs, and finally report newer experimental mobilization strategies employing novel agents that have been applied in other hematologic or solid malignancies.

Low-Toxicity/High-Efficacy HLA Haploidentical Transplantation for Elderly/Unfit Patients with Acute Leukemia

Allogeneic hematopoietic transplantation is the most powerful therapy for patients with acute leukemia at high risk of relapse. For HLA haploidentical transplantation, we recently applied a protocol consisting of a high-intensity TBI-based conditioning regimen and a peripheral blood CD34+ hematopoietic stem cell graft combined with the adoptive transfer of naturally occurring regulatory T cells (Tregs) and conventional T cells (Tcons). No post-transplant pharmacologic immune suppressive GvHD prophylaxis was given. Such a protocol was associated with remarkably low GvHD and relapse rates (Martelli MF et al., Blood. 124:638-644, 2014; reviewed in Mancusi A et al., Blood 128:2616-2623, 2016).However, patients who are unfit (because of multiple chemotherapy cycles, previous transplants, infections, or co-morbidities) or elderly are not expected to withstand high-intensity conditioning regimens. For these patients, we developed a reduced-toxicity version based on total marrow and total lymphoid irradiation (TMI/TLI) (Rosenthal J et al., Blood. 2011;117:309-315). TMI/TLI (13.5 Gy and 11.5 Gy respectively) were administered by means of Helical Tomotherapy HI-ART (in 9 fractions delivered two times a day in 4 and a half days). Target volumes were defined as the skeletal bone and major lymph node chains and spleen. In patients with ALL the brain was added as target volume. TMI/TLI was followed by chemotherapy with Thiotepa (2,5mg/kg/day for 2 days), Fludarabine (30 mg/m2/day for 5 days) and Cyclophosphamide (15 mg/kg/day for 2 days). As per our high-intensity protocol, the hematopoietic stem cell graft was foregone by an infusion of 2x10e6/Kg freshly isolated CD4/CD25/FOXP3-positive Tregs and a subsequent infusion of 1x10e6 Tcons. No post-transplant pharmacologic immune suppressive GvHD prophylaxis was given. To date 19 patients with high-risk acute leukemia in remission were enrolled (16 AML, 3 ALL). Median age was 57 years (range: 22-68). All patients engrafted. Four patients developed aGvHD grade ≥ 2. Transplant-related mortality was 21% (2 patients died of infections, 1 of VOD and 1 of aGvHD). Remarkably, no relapse or cGvHD were observed. With a median follow up of 12 months (range: 1-24), 15 of the 19 patients are alive. Thus, leukemia/cGvHD-free survival is 79%. Of course, these data need to be confirmed in a larger cohort of patients and with longer follow up.In conclusion, the present transplantation protocol was designed to make HLA haploidentical transplantation feasible and effective for unfit or elderly patients with high-risk leukemia. It combines a reduced-toxicity conditioning regimen with safe cellular immunotherapy of leukemia. To date, the clinical results are excellent and extremely encouraging. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Catheter-related bloodstream infection associated with multiple insertions of the peripherally inserted central catheter in patients with hematological disorders

Patients with hematological disorders are treated with multiple cycles of chemotherapy. As a result, they often require multiple insertions of the peripherally inserted central catheter (PICC) for prolonged periods of time. Although PICCs have been widely used worldwide in various patients, the safety and feasibility of the multiple insertions of the PICC in this population have not been fully verified. We performed a retrospective analysis to clarify the relationship between complications and multiple PICC insertions in patients with hematological disorders who were treated with either chemotherapy or immunotherapy. A total of 651 PICCs were inserted in 261 patients with a median age of 66 years. Acute myeloid leukemia (AML) and non-Hodgkin's lymphoma were the most common diseases in our patient cohort. The total catheter days (CDs) was 29,485 days, with a median catheter duration of 30 days. The rate of catheter-related bloodstream infection (CRBSI) in our patient cohort at high rate of re-insertion was 2.0/1000 CDs. Although multiple PICC insertions were not a risk factor of CRBSI, our findings suggest that a prolonged catheter dwell time may be associated with CRBSI. AML was an important risk factor of CRBSI. While the PICC dwell time depends on the treatment cycle, our findings indicate that it should be limited to approximately 30 days and catheters may be removed and re-inserted as needed.