Thrombocytopenia associated with ipilimumab therapy of advanced melanoma at a single institution.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9072-9072 ◽  
Author(s):  
Monique Z. Sajjad ◽  
Timothy George ◽  
Jeffrey S. Weber ◽  
Lubomir Sokol
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Case Series ◽  
Complete Response ◽  
Median Number ◽  
Hematologic Toxicity ◽  
Vascular Events ◽  
Normal Platelet ◽  
First Case ◽  
Pathology Reports ◽  
Steroid Refractory

9072 Background: Ipilimumab (IPi) is a monoclonal IgG1κ antibody targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) that was approved for the treatment of metastatic melanoma (MM). IPi therapy is associated with immune-related adverse events (irAEs) (Weber et al. J Clin Oncol2012 Jul 20;30(21):2691-7). Hematologic toxicity has rarely been reported. Methods: We analyzed 172 pts with MM treated adjuvantly or for metastatic disease with IPi on 2 clinical studies and an expanded access program (protocols MCC15283, MCC15722 and MCC15977). Clinical characteristics and hematologic parameters related to therapy were recorded. Medications, infections, comorbidities, prior therapies, and pathology reports from bone marrow (BM) biopsies were reviewed. Results: Of 172 subjects, 10 (5.8%) pts with normal platelet counts prior to therapy, developed thrombocytopenia (TCP) following IPi. Median number of doses was 8.5 (range 1-19). Median age at development of TCP was 64 years (range 21-93). Median time to development of TCP was 16.5 months (range 0.25 – 39). Of ten pts, three developed grade (gr) 1 or 2 TCP, three developed gr 3 and four pts developed gr 4 thrombocytopenia. BM analysis in pts with gr 4 TCP showed normal hematopoiesis and no evidence of melanoma. Six of 10 (60%) pts required therapy and were initiated on prednisone, but were deemed steroid refractory. No sustained responses to subsequent treatments with IVIG, rituximab, danazol, and/or splenectomy were observed. Three pts with grade 4 TCP were treated with eltrombopag. One of them achieved a sustained complete response lasting > 20 months. The other 2 pts who received eltrombopag discontinued treatment due to vascular events. Three out of 10 (30%) pts with any gr of TCP experienced mild bleeding episodes in the form of epistaxis. One pt with gr 4 thrombocytopenia experienced severe gastrointestinal bleeding requiring hospitalization. No deaths related to bleeding occurred. Conclusions: This is the first case series of hematologic irAEs in pts treated with IPi on clinical trials, suggesting that steroid refractory TCP may occur with IPi treatment . The timing and severity of IPi associated TCP is highly variable so careful hematologic monitoring should be considered.

Phase II study of weekly docetaxel plus cisplatin as first-line therapy in advanced or metastatic non-small cell lung cancer (CHN TAX-206)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18173-18173
Author(s):  
D. Chu ◽  
J. Li ◽  
X. Zhang ◽  
J. Liu ◽  
Z. Chen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Complete Response ◽  
Median Number ◽  
Common Adverse Event ◽  
Stage Iiib ◽  
Hematologic Toxicity ◽  
First Line ◽  
Weekly Administration ◽  
Weekly Docetaxel

18173 Background: There has been increasing interest in the use of weekly administration of docetaxel as a way of reducing its hemotologic toxicity. Weekly docetaxel plus cisplatin has also shown promising efficacy and well tolerability for first-line treatment of advanced or metastatic NSCLC in our previous phase I study (2002 ASCO, abstract No 2744). We conducted this phase II trial to further evaluate this regimen’s efficacy and toxicity. Methods: Patients with histologically confirmed stage IIIB or IV NSCLC were treated with docetaxel (35 mg/m2, 30 min. iv. infusion) on days 1, 8, 15 and cisplatin (75 mg/m2, 30 min. iv. infusion) on day 1 repeated every 4 weeks for up to 6 cycles. Pts received oral dexamethasone 7.5 mg twice daily from the day before chemotherapy and consecutive two days thereafter. The primary endpoint of this phase II study is efficacy of the regimen. Results: A total of 83 patients were enrolled from July 2002 to June 2004, 75 patients were evaluable for response and 83 for safety. Median age was 55 years (range 29–70 years); and 69.9% were male; adenocarcinoma/squamous cell carcinoma/others (65/12/6); stage IIIB /IV( 47/36); ECOG PS 0/1(52/31). Median number of chemotherapy cycles was 3(1–5). One CR (complete response) and 22 PR (partial response) were achieved with an ORR of 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3–34 months). Neutropenia was the most common adverse event, though most were mild; Grade III/IV toxicities per patient were: Neutropenia (15.6%), asthenia (11%), skin/nail toxicity (10.8%) and vomiting (9.6%). Febrile neutropenia was not observed. Conclusions: In the present study, the combination of weekly administration docetaxel combining with cisplatin appears well tolerated with very low frequency of severe hematologic toxicity and similarly efficacious as 3-weekly docetaxel in NSCLC pts. No significant financial relationships to disclose.

Case Report of Temozolamide Associated Steroid-Refractory ITP and Successful Treatment with Rituximab.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4015-4015
Author(s):  
Sandeep Reddy ◽  
Mark Janis ◽  
Mario Curti ◽  
Robert Minow
Keyword(s):  
Platelet Count ◽  
Successful Treatment ◽  
Platelet Transfusion ◽  
Original Diagnosis ◽  
Normal Platelet Count ◽  
Normal Platelet ◽  
First Case ◽  
Refractory Itp ◽  
Grade Iii ◽  
Steroid Refractory

Abstract We report the first case of temozolamide associated ITP and successful treatment with Rituximab. A 59 year-old male with grade III anaplastic astrocytoma is treated with resection followed by adjuvant temozolamide and gamma knife radiation therapy (XRT). He had been taking ramipril for hypertension, and atorvastatin for hyperlipidemia for greater than 1 year. He began taking phenytoin for seizure prophylaxis at the time of his original diagnosis in December of 2004. His CBC is normal at baseline. He recieves XRT from 2/1/05 until 2/15/05 with a normal platelet count of 142 on 4/21/05. He restarts temozolamide from 4/22 to 4/26 and presents with petechiae and platelet count 0. He receives platelet transfusion but platelet count remians at 3. A bone marrow biopsy confirms adequate megakaryoctes. He develops subcutaneous hemorrhage in the neck and is hospitalized for airway precautions. Prednisone at 2mg/kg and IVIG are given with no response. Rituximab is given weekly x 4 weeks at 375 mg/m2 with response by day 22 to platelet count of 123. The response is durable. See table 1. Response to Rituxan DATE PLATELET COUNT 6/1/05 3 6/16/05 9 6/23/05 104 6/30/05 123 7/21/05 118

Clinicopathological study of blue nevi of the gastrointestinal (GI) tract: first case series

2020 ◽  
pp. jclinpath-2020-206757
Author(s):  
Naziheh Assarzadegan ◽  
Kevan Salimian ◽  
Danielle Hutchings ◽  
Annika Lisbeth Windon ◽  
Lysandra Voltaggio ◽  
...  
Keyword(s):  
Case Series ◽  
Clinical Information ◽  
Endoscopic Examination ◽  
Gi Tract ◽  
Pigmented Lesions ◽  
First Case ◽  
Clinicopathological Findings ◽  
Pathology Reports ◽  
Middle Aged Adults

AimBlue nevus (BN) is a benign melanocytic proliferation that is typically cutaneous. Extracutaneous BN is infrequent and is reported in the mucosa of various organs. Gastrointestinal (GI) tract BN is rare. Here, we describe the clinicopathological findings of the largest series of GI tract BNs.MethodsA search of our Pathology Data System (1984–2019) identified six GI tract blue nevi. Clinical information, pathology reports and available H&E-stained section slides were reviewed.ResultsLesions predominated in the middle-aged adults (mean 54, range 27–80) with a slight female predominance (66%). Most cases arose in the rectum and colon (83%), with one gastric lesion (17%). Four cases were identified during endoscopic examination performed either for screening or for unrelated symptoms (66%). Two patients presented with rectal bleeding (33%) unassociated with the BN. Endoscopically, most lesions appeared as superficial hyperpigmented areas (83%). One case was described as abnormal mucosa (17%). Microscopically, the mucosa was involved in all of the cases (100%). One case showed submucosal extension in addition to the mucosal component (17%). Lesions showed a proliferation of bland spindle cells with abundant granular pigment. No nuclear atypia or mitoses were identified. Immunostains showed immunoreactivity for melanocytic markers. Follow-up information available for five patients showed no recurrences to date (mean follow-up 1 year).ConclusionsBN is a benign melanocytic proliferation. It is important to be aware of the occurrence of such lesions outside of the skin and consider the possibility of BN when pigmented lesions are encountered in the GI tract.

Decitabine (DAC) Can Be Safely Reduced After Achievement of Best Response In Patients (pts) with Myelodysplastic Syndrome (MDS)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1858-1858
Author(s):  
A. Megan Cornelison ◽  
Guillermo Garcia Manero ◽  
Hagop Kantarjian ◽  
Farhad Ravandi ◽  
Tapan Kadia ◽  
...  
Keyword(s):  
Research Funding ◽  
Performance Status ◽  
Objective Response ◽  
Complete Response ◽  
Median Number ◽  
Hematologic Toxicity ◽  
Phase Ii Trials ◽  
Free Survival ◽  
Maintenance Schedule ◽  
Best Response

Abstract Abstract 1858 DAC is standard therapy in pts with MDS. Current recommendations suggest a dose of 20 mg/m2 IV daily for 5 days every 4 weeks for as many cycles as possible to secure the best outcome. However, this therapy is associated with frequent grade 3–4 hematologic toxicity, requiring dose reduction (DR) and frequent dose delay (DD). We investigated the outcome of pts who had DD/DR and whether the timing of this dose modification relative to the time of response is relevant. Pts enrolled in phase II trials using DAC for frontline therapy for MDS were analyzed: 124 pts were treated at the dose of 10 mg/m2 IV daily × 10 days (n=17), 20 mg/m2 subcutaneously daily × 5 days (n=14), and 20 mg/m2 IV daily × 5 days (n=93). Median age was 65 years (range 37–90). Median follow up was 48 months. Seventy six pts responded, with 54 (44%) achieving a complete response (CR), 5 (4%) marrow CR, and 17 (14%) clinical benefit. The median transformation free survival (TFS) and overall survival (OS) was 13 and 20 months, respectively. Responders had better performance status (p=0.015), better baseline hemoglobin (p=0.006) and lower baseline blast percentage (p=0.05) than non responders. Sixty five pts (53%) had DR by at least 25% or DD (defined by a delay beyond 5 weeks between cycles) for a median of 7 days (range, 1 to 97), 25 had both. The main reasons for DR/DD were myelosuppression in 48 pts (74%) and infection in 10 pts (15%). Pts with DD/DR were more likely to have diploid cytogenetics (p=0.001) and received more DAC cycles (4 versus 11; p=0.001). There were no other statistically significant differences in characteristics between pts who had DD/DR versus those who did not. DD occurred after a median of 2 courses, with a median of 4 delays per pt (range, 1 to 22). DR occurred after a median of 7 courses (range, 2 to 24) with a median reduction of 25%. The median number of courses with DR was 6 (range, 1 to 18). Thirty five pts (54%) underwent DD/DR after achieving an objective response including 27 (42%) after CR. There was a trend for more durable responses in favor of pts requiring DD/DR after the achievement of an objective response (median not reached) compared to those who required DD/DR before (median of 18 months) (p=0.5). The 2-year OS rate trended higher for pts who had DD/DR after obtaining best response compared to those who had DD/DR prior to best response. The median OS was 30 and 22 months, respectively (p=0.15). There was no worsening in outcome when comparing pts who had no DD/DR to those who had DD/DR after the achievement of an objective best response. Transformation free survival (TFS) rates also trended higher for those with DD/DR after response compared to those who required DD/DR before. The median TFS was 27 and 18 months, respectively (p=0.12). In conclusion, DAC is effective in treating pts with MDS; DD/DR can be safely accomplished once the pt has achieved the best objective response (preferably CR) without impacting outcome. Prospective evaluation of an approach conceiving a loading dose for induction of a best objective response followed by a maintenance schedule is to be considered. Disclosures: Ravandi: Eisai: Honoraria, Research Funding. Cortes:Eisai: Research Funding.

Rituximab, gemcitabine, vinorelbine, and methylprednisone (R-GVM), a hematopoietic cell (HC) mobilizing and salvage regimen for malignant lymphoma (ML)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17537-17537
Author(s):  
A. Rezazadeh ◽  
G. Herzig ◽  
R. Herzig
Keyword(s):  
Previous Treatment ◽  
Complete Response ◽  
Median Number ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Salvage Regimen ◽  
Gm Csf ◽  
Treatment Regimens ◽  
Non Hodgkin Lymphoma ◽  
Cd34 Cells

17537 Background: The prognosis of pts with recurrent ML remains poor. High-dose therapy (HDT) with HC rescue can cure a proportion of such pts. HC mobilization can be adversely affected by number and duration of prior treatments, interval from diagnosis to HC collection, prior radiotherapy and marrow involvement. There remains a need for more effective and less toxic salvage regimens, capable of mobilizing HCs. Methods: The mobilizing potential of R-GVM salvage regimen with hematopoietic growth factor (HGF) support (G- and GM-CSF) was evaluated in 6 pts with relapsed (n=5) or primary refractory (n=1) ML. Pts received R-GVM salvage therapy [rituximab (375 mg/m2, day 1), gemcitabine (1 g/m2, day 1, 8), vinorelbine (30 mg/m2, day 1, 8) and methylprednisone (1 g/m2, day 1, 8)] with HGF administration and subsequent HC collection. The HGF support was started on day 9 and was continued through apheresis which started when the CD34+ cell count ≥ 20/μl (median day of R-GVM cycle: 15, range 14–19). Pts had daily apheresis with continued HGF support until at least 5 x 106 CD34+ cells/kg were collected. The hematologic and non-hematologic toxicity were tolerable in all pts; no pt required hospitalization. Results: 6 pts (age range 20–45 years) with Hodgkin (n =3) and non- Hodgkin lymphoma (n =3) were evaluated in this study. Pts had received 1–3 previous treatment regimens. The median number of R-GVM courses given before HC collection was 2.5 (range 1–5). Effective HC mobilization (≥5x106 CD34+ cells/kg) was obtained in all ps. A single apheresis resulted in satisfactory HC collection in 4 pts (range 8.2–17.7 x 106 CD34+ cells/kg); 2 pts required 3 aphereses to collect an adequate number of cells (6.7 and 7.4 x 106 CD34+ cells/kg). One pt was heavily pretreated and had failed two previous attempts of HC mobilization (one with HGF alone and one with cyclophosphamide and HGF); the other pt was HIV+ treated with HAART and had prior marrow involvement. As a salvage regimen, one pt had progressive disease, 1 had stable disease, 1 had a partial response, and 3 had a complete response before proceeding with HDT with HC rescue. Conclusions: R-GVM regimen is feasible, tolerable and effective in mobilizing HPC in patients with relapsed and refractory lymphoma. No significant financial relationships to disclose.

Effects of bevacizmab, eribulin and oxaliplatin in relapsed patients with platinum-resistant and refractory ovarian carcinomas: A preliminary case series with biomarker evaluation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17059-e17059 ◽  
Author(s):  
Jin Suminokura ◽  
Hiroko Kouta ◽  
Kazuya Kudoh ◽  
Miyuki Horikoshi ◽  
Tomoyuki Yoshikawa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
P53 Protein ◽  
Case Series ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Breast Cancers ◽  
Ovarian Carcinomas ◽  
Platinum Resistant ◽  
Previous Regimen

e17059 Background: Eribulin is a candidate for paclitaxel-refractory breast cancers, and Bevacizmab (B) is known to enhance efficacy of anti-cancer agents in ovarian cancers. A combination therapy using weekly administration of B with eribulin and oxaliplatin (EriOX) in relapsed patients with platinum-resistant and refactory ovarian carcinomas (PR-ROC) was evaluated retrospectively, and the association with response and serum biomarkers was investigated. Methods: Medical charts of the patients who met the criteria shown below were identified: (a) histologically confirmed epithelial ovarian cancer (b) diagnosed as platinum-resistant ovarian cancer (c) treated with weekly-B-EriOX consisting of B (2mg/kg), eribulin (1mg/m2), and oxaliplatin (30mg/m2), three weeks on and one week off, q4weeks (d) written informed consent. Biomarker analyses including serum VEGF, BNP, p53, and IL-6 were also conducted. Results: A total of 34 patients were treated with weekly-B-EriOX. Median age of the patients was 58.5 years (range: 35-76), and median number of previous regimen was 4(range: 2-9). Overall, two patients (6%) had a complete response (CR), 8 patients (24%) had a partial remission (PR) and 16 patients (47%) had a stable disease (SD). The response rate and clinical benefit rate (CR+PR+SD) were 29% and 76%, respectively. Median progression-free survival was 4 months (range: 1-27+). Hematological adverse effects (AE) with grade 3/4 were observed in 4 patients (11%). Non-hematological AE greater than grade 2 was observed in one case: hypo albuminemia and edema, which were manageable and tolerable. The patients with elevation of serum mutated p53 protein and IL-6 had poorer prognosis. Conclusions: Weekly B and EriOX administration showed a remarkable response for patients with PR-ROC. Elevation of serum mutated p53 protein and IL-6 could be biomarkers for this regimen. These results warrant further prospective studies with additional biomarker analyses.

scholarly journals Phase II trial of 2-chlorodeoxyadenosine for the treatment of cutaneous T-cell lymphoma [see comments]

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 906-911 ◽  
Author(s):  
TM Kuzel ◽  
A Hurria ◽  
E Samuelson ◽  
MS Tallman ◽  
HH Jr Roenigk ◽  
...  
Keyword(s):  
Median Duration ◽  
Group Performance ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Complete Response ◽  
Median Number ◽  
Infectious Complications ◽  
Hematologic Toxicity ◽  
Heavily Pretreated

We investigated the efficacy of 2-chlorodeoxyadenosine (2-CdA) therapy in patients with mycosis fungoides (MF) and the Sezary syndrome (SS). Between February 1991 and November 1993, 21 patients with relapsed or refractory MF/SS were treated with 2-CdA. 2-CdA was administered by continuous intravenous infusion at a dose of 0.1 mg/kg/d for 7 days initially (13 patients), but was subsequently reduced to 5 days (nine patients) due to hematologic toxicity. All patients had failed to respond to at least one prior treatment for MF/SS (median number of total prior therapies, five; median number of systemic prior therapies, three) and had an Eastern Cooperative Oncology Group performance status of two or better. Cycles were administered at 28-day intervals. Assessable patients received at least 5 days of 2-CdA. Fourteen patients received more than one cycle of 2-CdA. An overall response rate of 28% was achieved. Three patients (14%) had a complete response with a median duration of 4.5 months (range, 2.5 to 16). Three (14%) had a partial response with a median duration of 2 months (range, 2 to 4). Fifteen patients (72%) had no response. The most significant toxicities encountered were bone marrow suppression (62% of patients) and infectious complications (62% of patients). Thirty-eight percent of patients experienced no toxicity from 2-CdA. 2-CdA has activity as a single agent in patients with previously treated relapsed MF/SS. Studies in less heavily pretreated individuals with 2-CdA alone or in combination will be undertaken.

scholarly journals Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Hereditary Podocytopathies, Alport Syndrome, and FSGS: A Case Series to Better Plan a Large-Scale Study

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1815
Author(s):  
Jan Boeckhaus ◽  
Oliver Gross
Keyword(s):  
Glomerular Filtration ◽  
Alport Syndrome ◽  
Large Scale ◽  
Case Series ◽  
Hereditary Diseases ◽  
Glomerular Filtration Barrier ◽  
Early Effect ◽  
Filtration Barrier ◽  
First Case ◽  
Sodium Glucose Cotransporter

Hereditary diseases of the glomerular filtration barrier are characterized by a more vulnerable glomerular basement membrane and dysfunctional podocytes. Recent clinical trials have demonstrated the nephroprotective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in chronic kidney disease (CKD). SGLT2-mediated afferent arteriole vasoconstriction is hypothesized to correct the hemodynamic overload of the glomerular filtration barrier in hereditary podocytopathies. To test this hypothesis, we report data in a case series of patients with Alport syndrome and focal segmental glomerulosclerosis (FSGS) with respect of the early effect of SGLT2i on the kidney function. Mean duration of treatment was 4.5 (±2.9) months. Mean serum creatinine before and after SGLT-2i initiation was 1.46 (±0.42) and 1.58 (±0.55) mg/dL, respectively, with a median estimated glomerular filtration rate of 64 (±27) before and 64 (±32) mL/min/1.73 m2 after initiation of SGLT2i. Mean urinary albumin-creatinine ratio in mg/g creatinine before SGLT-2i initiation was 1827 (±1560) and decreased by almost 40% to 1127 (±854) after SGLT2i initiation. To our knowledge, this is the first case series on the effect and safety of SGLT2i in patients with hereditary podocytopathies. Specific large-scale trials in podocytopathies are needed to confirm our findings in this population with a tremendous unmet medical need for more effective, early on, and safe nephroprotective therapies.

scholarly journals CNS demyelination associated with immune dysregulation and a novel CTLA-4 variant

2021 ◽  
pp. 135245852096389
Author(s):  
Stefania Kaninia ◽  
Alexandros Grammatikos ◽  
Kathryn Urankar ◽  
Shelley A Renowden ◽  
Nikunj K Patel ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Novel Treatments ◽  
First Case ◽  
Self Tolerance ◽  
Autoimmune Conditions ◽  
History Of ◽  
Cns Demyelination

Background: The cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway acts as a negative immune regulator of T-cell activation and promotes self-tolerance. Case: We report the first case of biopsy-proven central nervous system inflammatory demyelination in the context of primary immunodeficiency and a novel CTLA-4 variant. Conclusion: This case has significant implications for the development of novel treatments for autoimmune conditions including multiple sclerosis and further emphasises the need for caution with clinical use of CTLA-4 immune checkpoint inhibitors in those with a history of inflammatory demyelination.

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