Incidence Of Severe Thrombocytopenia Research Articles

Adverse events and efficacy of second-round CAR-T cell therapy in relapsed pediatric B-ALL.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment approach for pediatric patients suffering from relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, there was a paucity of data on the challenges associated with second-round CAR-T therapy in this population. Medical records of nine pediatric patients who received second-round CAR-T therapy in a single center from June 2019 to May 2023 were analyzed. Throughout the course of the clinical trial, we evaluated adverse events including CRS, CRES, infections, hematologic toxicity, and organ injury, as well as CAR-T responses. Except for one patient who chose CART therapy due to testicular relapse, the remaining patients had indications for CAR-T therapy due to relapse with bone marrow alone or combined with other site. There were no difference between the transfusion dose of CART1 and CART2. No differences of incidence and grade of CRS was found between the first-round CAR-T therapy (CART1) and second-round CAR-T therapy (CART2). Additionally, we found that the incidence of CRES was higher for CART1(3/9,33.3%) than CART2(1/9,11.1%). Our findings revealed that there were no differences of IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α between CART1 and CART2, but the peak level of IL-17A was significantly higher in patients receiving CART1 compared to those receiving CART2 (p = .011). Early and late infection rates after CART1 were higher than CART2. Based on the dynamic changes of ANC, hemoglobin and platelet, ANC, and platelet were reduced obviously post CART. It seems that the incidences of severe thrombocytopenia and severe anemia were higher in the CART1 group compared to CART2. The MRD-negative CR rates for CART1 and CART2 are 100% and 44.4%, respectively (p = .029). All patients experienced events (relapse, chemotherapy, transplantation, or death) after receiving CART2, including one died, three discharged automatically, and the remaining five patients survived. Although the remission rate of CART2 is not as high as the CART1 due to the severity of the disease, its safety regarding CRS, CRES, infections, and organ injury is still excellent. Therefore, CART2 remains a viable option for treating pediatric relapsed B-ALL.

Predictive model for severe thrombocytopenia after transfemoral transcatheter aortic valve replacement.

The aim of this study was to develop a predictive model for severe thrombocytopenia after transfemoral transcatheter aortic valve replacement (TAVR). A total of 155 patients treated with TAVR at our center were retrospectively enrolled in this study. The incidence of severe thrombocytopenia after TAVR was 25.16%, and most patients suffered from severe thrombocytopenia on 4 days after procedure. Multivariate regression analysis showed that weight <60 kg, New York Heart Association Functional Classification (NYHAFC IV), major vascular complications, and lower first post-procedural platelet count were independent risk factors for severe thrombocytopenia after TAVR. The c-statistic for the area under the curve was 0.758, the sensitivity was 0.744, the specificity was 0.784, and the negative predictive value of the model was 91.38%. The overall predictive value was 76.77%. The predictive model developed from this cohort data could effectively identify patients at high risk of severe thrombocytopenia after TAVR, and might be applicable to patients with aortic regurgitation (AR) and severe thrombocytopenia with different definitions.

Association between Area under the Curve Estimated from Carboplatin Dose and Incidence of Severe Thrombocytopenia in Patients with Non-Hodgkin's Lymphoma on DeVIC Therapy.

The degrees of adverse effects with carboplatin (CBDCA) are influenced by interindividual differences in the area under the curve (AUC), whereas renal function is not considered in the CBDCA dose design for dexamethasone, etoposide, ifosfamide, and CBDCA (DeVIC) therapy. We conducted this study to evaluate the association between the AUC and incidence of severe thrombocytopenia in patients treated with DeVIC with or without rituximab (DeVIC ± R). We retrospectively analyzed clinical data for 36 patients with non-Hodgkin's lymphoma who received DeVIC ± R between May 2013 and January 2021 at the National Hospital Organization Hokkaido Cancer Center. The AUC of CBDCA (AUCactual) was calculated backward using a variant of the Calvert formula. The median AUCactual was 4.6 (interquartile range: 4.3-5.3) min mg/mL and AUCactual was negatively correlated with the nadir platelet count (r = -0.45; P < 0.01). Multivariate analysis showed that AUCactual ≥ 4.3 versus < 4.3 was an independent factor predictive of severe thrombocytopenia (odds ratio: 19.3, and 95% confidence interval: 1.45-258; P = 0.02). This study suggests that the CBDCA dosing design considering renal function can reduce the risk of severe thrombocytopenia in DeVIC ± R therapy.

Clinical characteristics and risk factors of 267 patients having severe fever with thrombocytopenia syndrome–new epidemiological characteristics of fever with thrombocytopenia syndrome: Epidemiological characteristics of SFTS

To analyze the epidemiological distribution, clinical characteristics, and prognostic risk factors of patients having severe fever with thrombocytopenia syndrome (SFTS). We enrolled 790 patients with SFTS divided into the ordinary group and the severe group, analyzed the clinical characteristics, and screened the risk factors of severious patients by univariate logistic regression analysis. Most of the 790 patients (SFTS) are farmers (84.56%). The proportion of patients with fieldwork history was 72.41%, of which 21.27% had a clear history of a tick bite and 98.61% were sporadic cases. The annual peak season is from April to November. 16.33% patients were not accompanied by fever. The incidence of severe thrombocytopenia was 47.59%. They were statistically significant between the 2 groups in indicators such as age, hypertension, coronary heart disease, diabetes mellitus, bunyavirus nucleic acid load and mean platelet count (P < .05). Multivariate non conditional Logistic regression analysis showed that the risk factors of the mild patients deteriorating severe disease were age (OR = 1.985, P ≤ .003), diabetes mellitus (OR = 1.702, P ≤ .001), coronary heart disease (OR = 1.381, P ≤ .003), platelet count (OR = 2.592, P ≤ .001), viral nucleic acid loading (OR = 3.908, P ≤ .001). The incidence population and seasonal distribution characteristics of patients with SFTS are obvious. The risk factors for poor prognosis of severe patients are old age, multiple basic medical histories, high viral load, a serious decrease of mean platelet count, and delay of treatment time.

Efficacy and toxicity of three concurrent chemoradiotherapy regimens in treating nasopharyngeal carcinoma: Comparison among cisplatin, nedaplatin, and lobaplatin.

Few studies directly compare efficacy and toxicity among lobaplatin, nedaplatin and cisplatin concurrently with intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). Totally 141 treatment-naïve NPC without distant metastasis receiving IMRT concurrent with cisplatin or nedaplatin or lobaplatin were retrospectively enrolled. Their response rate, toxicity and long-term survival were compared. Complete response (CR) rates of concurrent lobaplatin (CR-nasopharynx [CR-nx], 82.7%; CR-cervical lymph node [CR-nd], 94.2%) were lower than those of cisplatin (CR-nx, 89.3%; CR-nd, 98.2%) and nedaplatin (CR-nx, 93.9%; CR-nd, 97.0%), but statistical significance wasn't detected. Estimated five-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) weren't statistically significant between three groups. Multivariable analysis by COX proportional hazards model showed concurrent chemotherapy regimen wasn't an independent prognostic factor. Gastrointestinal toxicity was prevalent in platinum-based concurrent chemotherapy; cisplatin group suffered heavier (≥grade 2) than other two groups. More nephrotoxicity happened in cisplatin group (17.9%) than nedaplatin (9.1%) and lobaplatin (2.0%) groups. Incidence of dermatitis of ≥grade 2 was higher in cisplatin group (60.7%) than nedaplatin (27.3%) and lobaplatin (9.6%) groups. More patients in lobaplatin and nedaplatin groups suffered from any grade thrombocytopenia (P < .001), but incidence of severe thrombocytopenia (≥grade 3) was similar. Economic cost was significant less in lobaplatin group. Cisplatin, nedaplatin and lobaplatin are equally effective when used concurrently with IMRT in NPC. Lobaplatin and nedaplatin have potential to be alternatives to cisplatin in terms of less severe acute side-effects and economic cost.

Analysis of Related Factors of Autologous Peripheral Hematopoietic Stem Cell Mobilization in Patients with Lymphoma and Myeloma

To explore the related factors affecting of autologous peripheral hematopoietic stem cell mobilization in patients with single center lymphoma and multiple myeloma. The clinical total of 30 patients with lymphoma or multiple myeloma who underwent autologous peripheral hematopoietic stem cell mobilization and transplantation in the Affiliated Hospital of Jiangsu University from March 2012 to December 2021 were retrospectively analyzed, including the patients' age, gender, disease type, chemotherapy course, mobilization scheme, collection times, CD34+ cell count, adverse events, days of neutrophil and platelet implantation after transplantation. The related factors affecting to the mobilization efficiency of peripheral blood stem cells was analyzed. The mobilization scheme had a significant effect on the mobilization success rate of CD34+ cells. The mobilization success rate and optimal mobilization rate of intermediate-dose VP-16+G-CSF were higher than that of high-dose VP-16+G-CSF (P<0.05); the mobilization success rate of patients with previous chemotherapy courses ≤4 was higher than that of patients with chemotherapy courses >4 (100% vs 72.22%, P<0.05); the mobilization success rate of lymphoma patients was lower than that of myeloma patients (66.67% vs 94.44%, P<0.05); the mobilization success rate of lymphoma patients who received intermediate-dose VP-16+G-CSF was higher than that received high-dose VP-16+G-CSF patients (100% vs 42.86%, P<0.05). Patients' gender, age, time from diagnosis to mobilization and disease status had no significant effect on the efficiency of stem cell mobilization. Fifteen patients (50%) had febrile neutropenia during stem cell mobilization. There was no statistical difference in the incidence of febrile neutropenia between the two mobilization schemes (P>0.05); the incidence of severe thrombocytopenia in intermediate-dose VP-16+G-CSF group was higher than that in high-dose VP-16+G-CSF group (P<0.05). There was no statistical difference in the time of granulocyte implantation and platelet implantation after stem cell transplantation in patients with different mobilization schemes (P>0.05). Mobilization regime, the number of previous chemotherapy course and disease type affect the mobilization efficiency of stem cells. Intermediate dose VP-16+G-CSF can improve the mobilization efficiency of stem cell in lymphoma patients, but should pay attention to the risk of bleeding.

Safety of G-CSF with concurrent chemo-radiotherapy in limited-stage small cell lung cancer - Secondary analysis of the randomised phase 3 CONVERT trial

ObjectivesThe use of granulocyte colony-stimulating factors (G-CSF) during concurrent chemo-radiotherapy (cCTRT) for small cell lung cancer is not recommended by the American Society of Clinical Oncology due to safety concerns. This secondary analysis explored the safety and the role of prophylactic G-CSF (proG-CSF) in the delivery of cCTRT. Material and methodsSecondary analysis of 487 patients treated as per protocol on the phase 3 CONVERT trial which randomized patients between once-daily RT or twice-daily. Results180 of 487 eligible patients (37 %) received proG-CSF, 60 (33 %) as primary prophylaxis and 120 (67 %) as secondary prophylaxis following myelotoxic events. The regimen incidence of febrile neutropenia (FN) was 22 %. Its incidence in the proG-CSF group reduced significantly when proG-CSF was administered (22 % vs 10 %; OR 0.4; 95 %CI 0.2−0.7; p = 0.002). The rate of blood transfusion was higher in the proG-CSF group (51 % vs 31 %; OR 2.4; 95 %CI 1.6–3.5; p < 0.001). The incidence of severe thrombocytopenia was also higher is this group (28 % vs 15 %; OR 2.2; 95 %CI 1.4–3.5; p = 0.001). But this was significantly higher in those on secondary vs primary prophylaxis (34 % vs 15 %; OR 2.9; 95 %CI 1.3–7.4 p = 0.009) No differences observed in RT-related toxicity, treatment-related mortality or any survival outcomes. The optimal dose intensity (85 % or higher) of cisplatin was achieved in more patients within the proG-CSF group (75 % vs 67 %; OR 1.5; 95 %CI 0.9–2.3; p = 0.056). ConclusionThere was no evidence that G-CSF directly caused myelotoxicity, instead most patients started G-CSF due to higher myelotoxicity risk. G-CSF maintained the planned dose intensity and there was no detrimental effect on survival. G-CSF may be considered as a supportive measure in this setting.

Abstract 16543: Severe Thrombocytopenia is Common in Adults Undergoing Venoarterial Extracorporeal Membrane Oxygenation and is Predictive of Hemorrhage

Introduction: Extracorporeal membrane oxygenation (ECMO) is used to provide circulatory support and facilitate gas exchange via cardiopulmonary bypass. The relationship between ECMO and the incidence of severe thrombocytopenia (platelet count &lt;50 x 10 9 /L) and subsequent clinical consequences are ill defined. We aimed to identify the risk factors for the development of thrombocytopenia and its clinical implications. Methods: This is a single-center retrospective cohort study of adults who received venoarterial (VA) ECMO. We examined consecutive platelet counts while on ECMO. Univariate logistic regression was used to determine if mean platelet count, platelet count range, or severe thrombocytopenia were predictors of overall survival, hemorrhage and thrombosis. A multivariate logistic regression model was used to identify factors that contribute to the development of the aforementioned patient outcomes. Results: In our cohort, 33 patients were included with a mean age of 55 years and duration of ECMO of 5.9 days. All patients received heparin, 33.3% received antiplatelet therapy and 45.5% developed severe thrombocytopenia. In univariate, analysis the development of severe thrombocytopenia increased the odds of major bleeding by 450% (OR 5.500, 95% CI 1.219 - 24.813, P -value 0.027), and the odds of surviving hospitalization decreased 84.1% (OR 0.159, 95% CI 0.033 - 0.773, P -value 0.023). Multivariate logistic regression controlling for additional clinical variables found no significant association between the development of severe thrombocytopenia and rates of thrombosis, hemorrhage, or overall survival. Platelet count decreased over time while on ECMO. Conclusions: Nearly half of the patients requiring VA-ECMO developed severe thrombocytopenia, which was associated with an increased risk of hemorrhage and in-hospital mortality. Additional studies are required to clarify the clinical implications of severe thrombocytopenia in ECMO patients.

Type 2B Von Willebrand Disease in Pregnancy: A Systematic Literature Review [36K

INTRODUCTION: Type 2B Von Willebrand Disease (VWD) is a rare hereditary bleeding disorder that is associated with thrombocytopenia. Our objective was to review obstetric complications in women with Type 2B VWD. METHODS: A systematic literature search was conducted using PubMed, Scopus, and Cochrane Central Register of Controlled Trials to include all publications that address Type 2B VWD in pregnancy. Our primary and secondary outcomes were incidence of postpartum hemorrhage (PPH) and incidence of thrombocytopenia in pregnancy, respectively. RESULTS: 20 studies met inclusion criteria. There were 32 pregnancies with Type 2B VWD in 27 women. Primary PPH was reported in 9/20 (45%) and secondary PPH was reported in 6/13 (46%) and occurred between 5-32 days. Factor concentrate treatment was administered before delivery and postpartum in 16 and 18 pregnancies, respectively. 17 pregnancies required blood products postpartum. Platelet transfusion was given in 13/17 (76%) pregnancies. Red blood cell transfusion was performed in 6/17 (35%) pregnancies. Thrombocytopenia in pregnancy was reported in 27/28 (96%). 23/27 (85%) were severe thrombocytopenia with mean platelet count of 33.7±22.7 × 103/ul and 4/27 (15%) were mild thrombocytopenia (range, 126-150 × 103/ul). No maternal mortality was reported. CONCLUSION: Type 2B VWD in pregnancy has significant morbidity, with high incidence of primary and secondary PPH. The majority of patients required the use of factor concentrate before and after delivery in addition to postpartum blood products. The incidence of severe thrombocytopenia was also high, indicating that Type 2B VWD should be considered in the differential diagnosis of severe thrombocytopenia in pregnancy.

Incidence of Thrombocytopenia and Heparin Induced Thrombocytopenia in Patients Receiving Extracorporeal Membrane Oxygenation (ECMO) Compared to Cardiopulmonary Bypass and the Limited Sensitivity of Pre-Test Probability Score

IntroductionExtracorporeal membrane oxygenation (ECMO) is a life saving measure for severe respiratory (veno-venous ECMO [VV-ECMO]) or cardiac (veno-arterial ECMO [VA-ECMO]) failure. Heparin induced thrombocytopenia (HIT) is a special concern in these patients because ECMO uses a modified cardiopulmonary bypass (CPB) resulting in continuous exposure to artificial surfaces and unfractionated heparin (UFH) over several days to weeks, compared to CPB in which these exposures are for only a few hours. In addition, most of the patients undergoing CPB do not have underlying systemic inflammation and have a normal platelet count at the time of first exposure to UFH. It is possible that patients receiving ECMO are at higher risk of developing HIT compared to patients having CPB. The prevalence of HIT in adult patients receiving VV-ECMO is unknown.We determined to ascertain the incidence of thrombocytopenia and the reliability of pre-test probability score (PTPS) in predicting HIT, in patients receiving VV-ECMO or VA-ECMO compared to CPB. Differences in the PTPS of patients on ECMO compared to patients who received CPB and the effect of HIT on 30-day mortality in ECMO patients compared to patients who did not have HIT were also assessed.MethodsThis was a single centre retrospective study of patients undergoing CPB (median 4.6 [2-16.5] hrs. or receiving ECMO for ≥ 48hrs (median 7.1 [3-42] days. HIT screening was performed in all patients who showed a typical pattern of platelet drop in first 5 to 12 days after exposure to UFH with or without thrombosis. A citrated blood sample and a completed PTPS (4Ts) were collected from all patients prior to a screening test for HIT antibody performed on an ACL TOP500 analyser using Hemosil HIT-Ab (PF4-H) kit (Werfen UK). Those with positive HIT screening had confirmatory testing by ELISA (HYPHEN BioMed, France). Clinical data were collected from electronic records. From January 2016 to April 2018, 296 ECMO patients (142 VA-ECMO, 156 VV-ECMO) and 2998 CPB patients were studied.ResultsCPB patients were older than the patients who received ECMO; mean age (standard deviation) for EMCO and CPB were 45.4 (±15.6) and 64.9 (±13), p< 0.00001. A significantly higher proportion of men had CPB (71.3%) and ECMO (58.5%) than women, P<0.0001.Thrombocytopenia was divided into mild (platelet count 100-150x109/L), moderate (50-99x109/L) and severe (<50x109/L)). Table 1 demonstrates the percentages of patients in ECMO and CPB with different degrees of thrombocytopenia on day 1, 2, 5 and 10. The incidences of severe thrombocytopenia and moderate thrombocytopenia were 4.4% and 40% already on the first day of ECMO which were significantly higher than in patients having CPB (p<0.0001) and this difference remained significant in day 2, 5 and 10. The proportion of CPB patients with moderate thrombocytopenia rose to 32.4% on day 2 from 14.5% on day 1 but by day 10 platelet count was normal in 83% compared to 42.3 % patients receiving ECMO.A total of 96 patients had HIT screening tests (64/296 ECMO and 32/2988 CPB). Twenty patients (20/296, 6.8%) on ECMO (11/142, 7.7% VA-ECMO and 9/156, 5.8% VV-ECMO) had a positive screening test compared to 18 patients (18/2998, 0.6%) on CPB (p<0.001). All positive screening tests were confirmed by ELISA (100% positive predictive value). The median PTPS for patients on ECMO was 4 (3-7) whilst for patients who received CPB it was 5 (4-7). Four ECMO patients had PTPS of 3 and would not normally been screened according current guidelines. All patients with confirmed HIT were treated with argatroban. There was no difference in mortality between ECMO patients who did or did not developed HIT; overall mortality: 95/296, 32.1%, mortality in patients without HIT: 89/276, 32.2% and patients with HIT 6/20, 30%)In conclusion, severe and moderate thrombocytopenia is already common in patients receiving ECMO on the day of the ECMO initiation. Patients who had CPB dropped their platelet count to mild to moderate levels on day 2 and 5 and then recovered by day 10. HIT is more frequent in patients receiving ECMO (both VV and VA-ECMO) compared to patients who had CPB. Although the PTPS was good at predicting HIT in patients who had CPB, it failed to detect HIT in 4/20 (20%) ECMO patients. [Display omitted] DisclosuresJayakody Arachchillage:Bayer: Other: Sponsored to attend educational meetings; Octapharma: Other: Sponsored to attend an educational meeting; Mitsubishi Phama: Other: Sponsored to attend an educational meeting. Laffan:Roche: Consultancy, Speakers Bureau; Pfizer: Honoraria.

Lower‐dose intravenous immunoglobulins for the treatment of fetal and neonatal alloimmune thrombocytopenia: a cohort study

Intravenous immunoglobulins (IVIGs) are the cornerstone in the treatment of pregnancies at risk for fetal and neonatal alloimmune thrombocytopenia (FNAIT). The most commonly used dose is 1.0 g/kg/week, not based on any dose-finding study. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to describe the amount of severe thrombocytopenia according to two different doses of IVIG. We performed a cohort study, where two dosage regimes of IVIG were evaluated in the treatment of pregnant women suffering from FNAIT with a previous affected child without intracranial hemorrhage (ICH). Cases, treated with 0.5 or 1.0 g/kg/week, were selected from the international multicenter No IntraCranial Hemorrhage (NOICH) registry. Outcome was neonatal platelet (PLT) count at birth and amount of severe thrombocytopenia. Furthermore the appearance of ICH was analyzed. A total of 109 women were included in the study, 46 in the 0.5 IVIG group and 63 in the 1.0 IVIG group. There was no difference in PLT count at birth (mean, 112 vs. 119; crude difference, 7; confidence interval [CI], -37.4 to 23.7]) and incidence of severe thrombocytopenia (<30×10(9) /L; n=7/46 vs. n=7/63; odds ratio, 1.43 [CI, 0.46-4.42]). No ICH occurred. In pregnancies with FNAIT with a previous affected child without ICH, treatment with IVIG in a weekly dose of 0.5 or 1.0 g/kg results in comparable neonatal PLT count at birth and degree of thrombocytopenia.

Changes in the incidence of severe thrombocytopenia and its predisposing conditions in HIV-infected patients since the introduction of highly active antiretroviral therapy.

Severe thrombocytopenia (TCP, platelets <50 × 10⁹/L) is relatively frequent during HIV infection and is associated with bleeding risk and disease progression. We investigated the changes in the incidence of severe TCP and its predisposing conditions in a cohort of HIV-positive subjects. The incidence and predictors of platelet counts <50 × 10⁹/L were investigated in all patients enrolled at our institution between 1985 and 2012. Three different periods were considered on the basis of the available antiretroviral regimens: P1 (1985-1989), P2 (1990-1996), and P3 (1997-2012). Incidence rates were assessed using Poisson regression models and the predictors by means of Cox regression. The study involved 5137 patients with platelet counts >50 × 10⁹/L at enrollment. Severe TCP occurred in 597 subjects, and its incidence decreased over time. The incidence decreased in patients with opportunistic diseases and malignancies but increased in patients with chronic liver disease; TCP unrelated to any cause other than HIV infection remained stable. Multivariate analysis showed that injected drug use, a diagnosis of AIDS, low CD4⁺ cell counts, increased serum alanine aminotransferase levels, and an earlier year of enrollment were predictors of an increased risk of severe TCP, whereas the use of highly active antiretroviral therapy (HAART) was associated with a reduced risk. A considerable reduction in the incidence of severe TCP after the introduction of HAART was found, probably because of its ability to limit bone marrow damage induced by uncontrolled HIV replication and opportunistic infections. On the contrary, HAART may have a reduced impact on TCP related to chronic liver disease.

Severe Thrombocytopenia and Its Clinical Impact After Implant of the Stentless Freedom Solo Bioprosthesis

This single-center study analyzed the occurrence of severe thrombocytopenia and its clinical effect after concomitant and isolated aortic valve replacement (AVR) with the stentless Freedom Solo (FS) prosthetic valve (Sorin Group, Saluggia, Italy). Between October 2009 and February 2012, 151 consecutive patients underwent AVR with a FS, either isolated (lone-FS group) or concomitant with another procedure (all-FS group). These groups were compared with 152 consecutive patients implanted with a stented Edwards Lifesciences Perimount (EP) bioprosthesis (Edwards Lifesciences, Irvine, CA). Primary end point was the incidence of severe thrombocytopenia (platelet count < 50 × 10(9)/L). Secondary end points were clinical outcomes, administered transfusions (red blood cells, thrombocytes, frozen plasma), and adverse events. Rinsing the FS before implantation with saline solution was also evaluated. Platelet counts were significantly lower in the all-FS and lone-FS groups than in the EP group during the first 5 days (p < 0.001). Average nadir was 102 ± 50 in lone-FS group and 130 ± 35 in lone-EP group (p < 0.001). Independent predictors for severe thrombocytopenia were FS, body surface area, and preoperative platelet count. No significant difference was found in transfusions or adverse events. Intensive care unit stay was slightly increased in the lone-FS group (p = 0.04). Rinsing the FS did not prevent thrombocytopenia. AVR with FS was associated with severe thrombocytopenia during the first postoperative days. Besides a slightly longer hospitalization in the intensive care unit in the FS group, the clinical outcome did not differ significantly, indicating thrombocytopenia was a transient and self-recovering phenomenon, not affecting clinical outcome. Rinsing the FS did not prevent thrombocytopenia.

Retrospective Analysis of Thrombocytopenia in Relapsed Multiple Myeloma Patients

Abstract 5073 IntroductionDespite improvement in patient (pt) outcomes in recent years, multiple myeloma (MM) remains incurable and nearly all pts relapse after initial response to therapy. With disease progression and cumulative exposure to chemotherapeutic agents, pts with relapsed MM frequently develop cytopenias that represent a significant clinical challenge. At present, management of high-grade thrombocytopenia at our institution consists of supportive platelet transfusions. We hypothesize that thrombocytopenia is a highly relevant variable in the overall management of relapsed MM. As there are currently no studies in the myeloma literature that assess the impact of thrombocytopenia, we conducted a retrospective, chart-review study to evaluate the impact of thrombocytopenia in relapsed MM. MethodsParticipants included all pts with relapsed and/or relapsed-refractory MM who participated in clinical trials at Dana Farber Cancer Institute from January 1, 2007 – December 31, 2009. Many pts participated in more than one clinical trial during this time period. In this analysis, therapy administered to a particular patient in the context of one clinical trial is referred to as a “treatment regimen.” The overall incidence of thrombocytopenia (platelet count < 150,000/mcl) at initiation of a treatment regimen was recorded. The incidence of severe thrombocytopenia (platelet count < 100,000/mcl and < 75,000/mcl) was also determined. Medical record data collected to assess the clinical impact of thrombocytopenia included the following variables: episodes of ≥ grade 3 thrombocytopenia, number of platelet transfusions per pt per month on clinical trial, treatment delays and treatment discontinuations due to thrombocytopenia, the occurrence of bleeding events, and overall survival on clinical trial therapy. Point estimates with exact binomial confidence intervals and median and range are used to describe the data. The differences in platelet transfusion requirements were assessed by the two-sided Wilcoxon rank sum test. ResultsTo date, data has been abstracted on 43 treatment regimens in 23 pts. Fifteen pts had previously undergone autologous stem cell transplantation (ASCT), including two who had undergone tandem auto-transplant. The overall incidence of thrombocytopenia (platelet count < 150,000/mcl) was 40% at time of treatment initiation. In 13 of the 43 (30%, 90% Confidence Interval (CI)) treatment regimens, the platelet count at time of treatment initiation was less than 100,000/mcl. The platelet count at time of treatment initiation was less than 75,000/mcl in 11 of 43 (25%, 90%CI) treatment regimens reviewed. Cases where the platelet count was ≤ 100,000/mcl at time of study entry, mean platelet transfusion requirement per 4-week time interval was 2.35 units, while in cases where the platelet count was ≥ 100,000/mcl, the mean platelet transfusion requirement was 0.20 units transfusions per 4 week period was needed (p <.0001). In 20 (47%, 90% CI) of the treatment regimens reviewed, bortezomib was part of the therapeutic regimen. Data revealed no significant difference in requirement for platelet transfusion between regimens that included bortezomib versus those that did not. Two pts experienced a bleeding event during their treatment regimens. The platelet count at the time of the bleeding events was 57,000/mcl and 154,000/mcl. Treatment was delayed for one pt due to thrombocytopenia, and two pts were removed from study due to thrombocytopenia. Overall rate of survival at 1-year among 23 pts assessed to date was 91%. ConclusionThrombocytopenia is a common problem in this pt population, particularly in pts that begin treatment with a platelet count < 100,000/mcl. This results in increased platelet transfusions, which are associated with heightened cost of health care and risk of transfusion related toxicities (ex. platelet alloimmunization). Complications related to thrombocytopenia such as bleeding events and treatment discontinuation are relatively rare; this is likely due to routine use of platelet transfusion. Of note, the incidence of transfusion is likely underrepresented by this retrospective study because intact bone marrow function is an eligibility criterion for most clinical trials involving pts with relapsed MM. This data supports the need for improved therapies that minimize transfusion support in this population. Disclosures:Richardson:Millennium:; Celgene:; Johnson & Johnson:; Novartis:; Bristol Myers Squibb:. Anderson:Celgene: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

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Gemcitabine and Carboplatin in Intensively Pretreated Patients with Metastatic Breast Cancer

Background: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. Patients and Methods: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m² i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. Results: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17–48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6–6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7–16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombocytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. Conclusion: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m².

Incidence and significant predicting factors for chemotherapy-induced severe thrombocytopenia in lymphoma patients

20519 Background: Severe thrombocytopenia (TCP) is a complication of chemotherapy (CT), resulting in frequent transfusions and treatment delays. The incidence and risk factors for TCP in lymphoma patients (pts) with current CT regimens are not well defined. Methods: Medical records of 1046 newly referred lymphoma pts to MD Anderson Cancer Center in 2003 were retrospectively reviewed over two years follow-up period. The incidence of severe TCP was determined, and logistic regression models were employed to identify the significant baseline clinical and laboratory features correlated with severe TCP. Results: 404 pts, who received ≥ 1 cycle of treatment and had adequate laboratory records, were included in the analysis (total CT cycles 2061). Grade (GR) 4 TCP (PLT nadir < 25×103/μL) was observed in 42% (170/404) of pts, in the median cycle 2 (range 1-11) and median PLT nadir of 12×103/μL (1- 24×103/μL). Bleeding occurred in 48% (81/170) of pts with GR 4 TCP compared to 8% (19/234) of pts with higher PLT counts (p=0.0001), although most bleedings (95%) were minor. Seventy-nine percent (134/170) of pts with GR 4 TCP received PLT transfusions, compared to only 2% (4/234) of pts with higher PLTs (p<0.0001). 137 out of 170 (81%) GR 4 TCP pts and 245 out of 398 (62%) GR 4 TCP episodes occurred in the 1st regimen. Therefore the logistic regression models analyzed the data set of 1st regimen. In the multivariate model, following variables were most important predictive factors for GR 4 TCP. Conclusions: The incidence of severe TCP in lymphoma pts is high. Predictive risk factors can be very useful to develop prophylactic strategy with PLT growth factors in high risk pts to prevent TCP related complications. Variable Odds Ratio (95% CI) P value Myelosuppressive Risk of Regimen ( high vs low) 38.60 (18.70–79.66) <0.0001 Extra Nodal Involvement (yes vs no) 2.57 (1.29–5.09) 0.007 Type of Previous Therapy* (CT+RT vs no Rx) 3.53 (1.33–9.33) 0.011 PLT Count 0.995 (0.993–0.998) 0.001 Serum Beta2MicroG 1.153 (1.03–1.29) 0.014 * RT: radiotherapy; no statistical significance between RT or CT±surgery vs no Rx. No significant financial relationships to disclose.

Clinicopathological diagnosis and treatment of malignant histiocytosis

The diagnostic findings of malignant histiocytosis (MH) were analysed in 12 consecutive patients in a single institution. Most patients presented with systemic symptoms and lymphadenopathy (92%), splenomegaly (100%) and hepatomegaly (67%). Neurologic symptoms were present in three patients, while involvement of other organs was present in five patients. The incidence of severe thrombocytopenia was 92% of anaemia 92% and of leucocytopenia 67%. Serum angiotensin converting enzyme, alpha 1-antitrypsin and lysozyme were independently increased in 6/9, 3/10 and 1/9 patients respectively. High serum levels of tumour necrosis factor (TNF) were present in 3/10 patients, while serum levels of interleukin-1 were normal in 10/10 patients. Histologic evidence of MH was obtained in all patients by repeated biopsies of involved tissues. Four patients died prior to treatment. Seven patients were treated with combination chemotherapy, consisting of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or MOPP (chloromethine, vincristine, procarbazine, prednisone), in some cases followed by non-cross-resistant second line chemotherapy, if no complete response was attained. The response rate of treated patients was 57%, and progression was observed in two patients. The median duration of response was 38 months. Three patients are alive without evidence of disease and off therapy (30+, 83+, 85+ months). Although MH is a potentially lethal disease, combination chemotherapy may offer a chance for cure in some patients.