Late Breaking Abstract: ASH – 2023: Pomalidomide Reduces Epistaxis and Improves Quality of Life in Hereditary Hemorrhagic Telangiectasia

SUMMARY: Hereditary Hemorrhagic Telangiectasia (HHT) is an Autosomal Dominant inherited disorder caused by mutations in regulators of angiogenesis. Also known as Osler-Weber-Rendu syndrome, HHT is the second most common inherited bleeding disorder after Von Willebrand Disease, with an estimated prevalence of 1 in 5000. HHT presents with a triad of recurrent epistaxis with iron deficiency anemia, mucocutaneous telangiectasias, and visceral arteriovenous malformations (AVMs) and in more severe cases, patients may experience life-threatening hemorrhage, stroke, or high-output heart failure, requiring hospitalizations, with a negative impact on Quality of Life (QOL). HHT is caused by disruptions in angiogenesis signaling, resulting in impaired vascular development. Three genes in the Transforming Growth Factor-beta (TGF-β) signaling pathway have been implicated and they include Endoglin (ENG), activin A receptor ligand type I (ACVRL1 or ALK-1), and SMAD family member 4 (MADH4 or SMAD4).

Small non-randomized studies suggested that systemic antiangiogenic agent Bevacizumab or immunomodulatory drugs with antiangiogenic properties such as Thalidomide, Lenalidomide, and Pomalidomide may be effective in treating HHT. There are presently no FDA approved therapies for HHT.

PATH-HHT is a randomized, placebo-controlled, multicenter clinical trial, conducted in the US to determine the safety and efficacy of Pomalidomide, for bleeding in HHT. In this study, 144 patients (N=144) diagnosed with HHT were randomly assigned in a 2:1 ratio to receive either Pomalidomide 4 mg orally daily or a matching placebo, for a duration of six months. Pomalidomide, instead of another immunomodulatory drug, was chosen due to its favorable safety profile. Eligibility criteria included a confirmed HHT diagnosis per Curaçao Diagnostic Criteria, documented anemia, and an Epistaxis Severity Score (ESS) of 3 or more over the prior 3 months. Epistaxis Severity Score (ESS) was developed to self- describe epistaxis severity from 0-10, with 10 representing the most severe epistaxis. Mild is ESS of 1-4, moderate is ESS of 4-7 and Severe is ESS of 7-10. The mean age was 59 years and 48% were female. Among the 134 patients who agreed to genetic testing, ENG mutations were detected in 37%, ACVRL1 in 51%, and SMAD4 in 1%. Patients had a mean ESS of 5 at baseline, and mean daily epistaxis duration of 16 minutes. In the preceding 6 months, 84% of patients had required iron infusions and 19% required blood transfusions. More than a third of the patients also had GI bleeding, and 40% had pulmonary AVMs. The Primary endpoint of the study was the change in Epistaxis Severity Score (ESS), from baseline to the end of the six-month treatment period. Secondary endpoints included changes in the average daily self-reported duration of epistaxis from the 4 weeks preceding the baseline visit to weeks 20-24 of treatment, the amount of parenteral iron infused or blood transfused, and change in Quality-of-Life (QOL) measurements, including an HHT-specific QOL score.

The results of this study showed that treatment with Pomalidomide led to a significant reduction in epistaxis severity compared to placebo. The mean ESS decreased by -1.84 in the Pomalidomide group versus -0.89 in the placebo group at 24 weeks (P=0.003). This benefit was seen as early as week 12. Additionally, patients treated with Pomalidomide reported greater improvements in Quality of Life (QOL) related to HHT. The HHT-specific QOL score (ranges from 0-16 with higher scores indicating more limitations) also decreased more in the Pomalidomide group versus the placebo group at 24 weeks (P=0.015). Adverse events were more common in the Pomalidomide group and included mild to moderate neutropenia (45% versus 10%), constipation/diarrhea (60% versus 37%), and rash (36% versus 10%).

It was concluded from this largest HHT study that treatment with Pomalidomide demonstrated a significant and highly clinically relevant reduction in epistaxis, as well as an improvement in the HHT-specific QOL score. Pomalidomide holds promise as a therapeutic option for patients with HHT, addressing an unmet medical need, in managing this challenging genetic disorder. Additional studies may identify biomarkers predicting responses to Pomalidomide.

PATH-HHT, a Double-Blind, Randomized, Placebo-Controlled Trial in Hereditary Hemorrhagic Telangiectasia Demonstrates That Pomalidomide Reduces Epistaxis and Improves Quality of Life. Al-Samkari H, Kasthuri RS, Iyer V, et al. Blood (2023) 142 (Supplement 2): LBA-3. https://doi.org/10.1182/blood-2023-191983.

ROZLYTREK® (Entrectinib)

The FDA on October 20, 2023, granted accelerated approval to ROZLYTREK® for pediatric patients older than 1 month with solid tumors that have a Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory standard therapy. In August 2019, FDA granted accelerated approval to ROZLYTREK® for pediatric patients 12 years of age and older for this indication. ROZLYTREK® is a product of Genentech Inc.

TEMODAR® (Temozolomide)

The FDA on September 14, 2023, approved updated labeling for TEMODAR® under Project Renewal, an Oncology Center of Excellence (OCE) initiative aimed at updating labeling information for older oncology drugs to ensure information is clinically meaningful and scientifically up-to-date. This is the second drug to receive a labeling update under this pilot program. The first drug that received approval under Project Renewal was XELODA® (Capecitabine). TEMODAR® is a product of Merck & Co., Inc..

HEPZATO® KIT (Melphalan for Injection/Hepatic Delivery System)

The FDA on August 14, 2023, approved HEPZATO® KIT as a liver-directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation. HEPZATO® is a product of Delcath Systems, Inc.

Single Blood Test for Multi-Cancer Early Detection

SUMMARY: The American Cancer Society estimates that in 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Although cancer mortality rates continue to decline with advances in treatment, improving early detection can reduce disease and treatment-related morbidity, improve treatment outcomes, quality of life and reduce financial burden both for the patient as well as the society as a whole. Currently the USPSTF (Unites States Preventive Services Task Force) and ACS (American Cancer Society) recommend screening for breast, cervical, colorectal, and lung cancers. Neither the ACS nor USPSTF have specific recommendations for prostate cancer screening. These cancers collectively account for only 42% of annual cancer incidence in people aged 50-79 years. It has been estimated that detection of cancer at an earlier stage could reduce cancer-related deaths by 15% or more within 5 years. Some of the available screening tests reduce cancer-specific mortality, but are associated with high false-positive rates, overdiagnosis, and overtreatment.

Galleri is a Multi-Cancer Early Detection (MCED) test developed for the early detection of multiple asymptomatic cancers that lack recommended screening tests, using a blood sample. DNA (cell free DNA) is shed into the blood stream both by tumor cells as well as healthy cells. The Galleri test uses Next Generation Sequencing (NGS) and machine-learning algorithms to isolate cell-free DNA and analyze more than 100,000 DNA regions and over a million specific DNA sites, to screen for a signal shared by cancers. The test looks for cell-free DNA and identifies whether it comes from healthy or cancer cells. DNA from cancer cells has specific methylation patterns that identify it as a cancer signal. Methylation patterns also contain information about the tissue type or organ associated with the cancer signal. So, once a cancer signal is detected, the Galleri test predicts the Cancer Signal Origin, or the tissue or organ where the cancer signal originated, to help guide diagnostic evaluation. The Galleri test is recommended for use in adults with an elevated risk for cancer, such as those aged 50 or older, and should be used in addition to routine cancer screening tests. Galleri is not recommended in individuals who are pregnant, 21 years old or younger, or undergoing active cancer treatment.

A validation study (Circulating Cell-free Genome Atlas study-CCGA) was conducted to evaluate the accuracy of the Galleri test. This study included 2,823 people with a known diagnosis of cancer and 1,254 healthy people. The overall Sensitivity for cancer signal detection was 51.5% and the Specificity was 99.5%. The sensitivity of the test increased with advanced cancer stages. Cancer signals were detected across over 50 cancer types and the overall accuracy of predicting Cancer Signal Origin in those who tested true positive was 88.7% (Ann Oncol. 2021;32:1167-1177).

PATHFINDER was a pilot, prospective cohort study conducted to investigate the feasibility of MCED testing for cancer screening. This study included 6,621 participants from oncology and primary care outpatient clinics at seven U.S. health networks who underwent MCED blood testing. Participants were 50 years or older, with no signs or symptoms of cancer, and majority were women (63.5%) and White (91.7%). Approximately 56% of participants had additional risk factors such as smoking, germline cancer predisposition, or personal history of treated cancer. The Primary outcome was time to diagnosis, and extent of diagnostic testing required to confirm the presence or absence of cancer.

MCED testing detected a cancer signal in 1.4% of the total patient sample of whom 38% had cancer confirmed (true positives), while 62% had no cancer (false positives). In patients in whom no cancer signal was detected, 95.5% were true negatives, 1.3% was false negatives, and 3.2% did not have cancer-status assessment at the end of the study. The tests accuracy in predicting the primary cancer location (Cancer Signal Origin) among the true positives was high at 97%. The median time to achieving a diagnostic resolution was 79 days, 57 days in true-positive patients and 162 days in false-positive ones. Fewer procedures were done in participants with false-positive results compared to true-positive results (30% versus 82% respectively) and few participants had surgery (one with a false-positive result and three with a true-positive result).

Among participants whose testing was true-positive and who had a confirmed new cancer diagnosis, nearly half (48%) were detected at an early stage (Stage I-II) when the potential for curative treatment is increased. Further, 74% of the MCED-detected cancers were cancer types that do not currently have USPSTF screening recommendations. These included cancers of the bile duct, pancreas, small intestine, and spindle cell neoplasm, which are all associated with high mortality rates and may be amenable to surgical resection at early stages.

In the 12 months study period, 121 cancers were diagnosed, of whom 29% had a cancer signal detected by MCED, while 31% were detected thru screening and 40% were detected clinically. The overall Positive Predictive Value of MCED was 38%, Negative Predictive Value was 98.6%, and specificity was 99.1%. The cancer yield rate was 0.53% (number needed to screen to find one MCED-detected cancer was 189).

The researchers concluded that this study demonstrates the feasibility of screening for multiple cancers using a blood test and lays the foundation for large, controlled trials necessary to establish clinical utility and cost-effectiveness. Multi Cancer Early Detection test was also able to accurately predict tumor origin, and the diagnosis of cancer was established in less than 2 months in the true-positive patients.

Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study. Schrag D, Beer TM, McDonnell CH, et al. The Lancet 2023;402:1251-1260.

Non-Hormonal Treatments for Menopausal Symptoms – NA Menopause Society 2023 Position Statement

SUMMARY: It is estimated that the 50 million women will attain menopause annually. Natural menopause occurs in women between age 49-52 years. Vasomotor symptoms (VMS) manifesting as hot flashes and night sweats are the most common symptoms of menopause. These symptoms occur in up to 80% of menopausal women lasting from 7-10 years and sometimes even longer, significantly impacting their quality of life. Compared to other ethnic groups, menopausal symptoms tend to be less severe in Asian women and more severe in African American women.

Hormone Replacement Therapy remains the most effective treatment and should be considered in menopausal women younger than 60 years, within 10 years of their final menstrual periods, with no contraindications. However, the use of Hormone Replacement Therapy has declined substantially, following the Women’s Health Initiative (WHI) hormone therapy trials recommendation, not to prescribe menopausal hormone therapy for chronic disease prevention due to the complex pattern of risks and benefits, including increases in invasive breast cancer, stroke and pulmonary embolism.

Nonhormonal interventions have therefore been important considerations for symptomatic menopausal women. The North American Menopause Society convened an advisory panel of clinicians and research experts in the field of women’s health, to review and evaluate the literature published after the Position Statement of The North American Menopause Society in 2015.

This advisory panel assessed the most current and available literature to recommend or not recommend use, with the level of evidence assigned, on the basis of these categories:

• Level I: Good and consistent scientific evidence.
• Level II: Limited or inconsistent scientific evidence.
• Level III: Consensus and expert opinion

The following are the evidence-based updated guidelines:

Level I
Cognitive-Behavioral Therapy: CBT has been shown to reduce the bother and interference associated with VMS.
Clinical hypnosis: Clinical hypnosis has been shown to reduce VMS frequency and severity.
Selective Serotonin Reuptake Inhibitors (SSRIs)/ Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): SSRIs and SNRIs are associated with mild to moderate improvements in vasomotor symptoms.
SSRIs: Paroxetine 7.5 mg daily is approved by the FDA for the treatment of moderate to severe vasomotor symptoms. Paroxetine however should be avoided in women taking Tamoxifen to treat or prevent breast cancer. Other SSRIs include Citalopram and Escitalopram which have less of an effect on the CYP2D6 enzyme.
SNRIs: Venlafaxine may be a safer choice in women using Tamoxifen as coadministration of SSRIs such as Paroxetine or Fluoxetine with Tamoxifen may lead to inhibition of CYP2D6 (the enzyme that converts Tamoxifen to its most active metabolite, endoxifen).
Gabapentin: Gabapentin is approved by the FDA as an antiepileptic drug, and is often used to treat diabetic neuropathy and postherpetic neuralgia. However, several trials studying the dose of 900 mg (300 mg three times/day) show that this has improved the frequency and severity of vasomotor symptoms.
Fezolinetant (VEOZAH®): Fezolinetant is a first-in-class neurokinin B antagonist that is FDA approved for management of vasomotor symptoms. It modulates the neuronal activity in the thermoregulatory center of the brain.
Oxybutynin: Oxybutynin is an antimuscarinic, anticholinergic therapy that is used for the treatment of overactive bladder and urinary urge incontinence. Oxybutynin has been shown to reduce moderate to severe vasomotor symptoms, although in older adults, long-term use may be associated with cognitive decline
Pregabalin and Clonidine are not recommended for vasomotor symptoms

Level II-III
Weight Loss: The limited available evidence suggests that weight loss may be used to improve vasomotor symptoms for some women.
Stellate ganglion blockade: This procedure is a widely used to treat migraine and complex regional pain syndrome by injecting an anesthetic agent at the lower cervical or upper thoracic region. This blockade might help alleviate moderate to very severe vasomotor symptoms in select women. Because of the potential risks and adverse events, its potential use for vasomotor symptoms should be carefully evaluated.

The following interventions have NOT BEEN PROVEN beneficial and NOT RECOMMENDED interventions:
Paced respiration, Supplements/Herbal remedies, avoiding triggers such as alcohol, caffeine, spicy foods or hot foods, Cooling techniques, Exercise, Yoga, Mindfulness-based intervention such as meditation, Relaxation, Suvorexant, Soy foods and Soy extracts, Soy metabolite equol, Cannabinoids, Acupuncture, Calibration of neural oscillations, Chiropractic interventions, and Dietary modification.

The panel concluded that the most effective treatment for vasomotor symptoms is hormonal therapy and should be considered in menopausal women within 10 years of their final menstrual periods. For women who are not candidates for hormone therapy because of contraindications (estrogen-dependent cancers or cardiovascular disease) or personal preference, it is important for healthcare professionals to be well informed about the evidence-based nonhormone treatment options, for reducing vasomotor symptoms.

NAMS POSITION STATEMENT: The 2023 nonhormone therapy position statement of The North American Menopause Society. Menopause: The Journal of The North American Menopause Society 2023;30:573-590. DOI: 10.1097/GME.0000000000002200

OMISIRGE® (Omidubicel-onlv)

The FDA on April 17, 2023, approved OMISIRGE® for use in adult and pediatric patients (12 years and older) with hematologic malignancies who are planned for umbilical cord blood transplantation following myeloablative conditioning, to reduce the time to neutrophil recovery and the incidence of infection. OMISIRGE® is a product of Gamida Cell Ltd.

Late Breaking Abstract – ASCO 2023: ENHERTU® Effective in Multiple HER2 Expressing Solid Tumors

SUMMARY: The HER or erbB family of receptors consist of HER1, HER2, HER3 and HER4. Approximately 15-20% of invasive breast cancers as well as advanced Gastric and GastroEsophageal (GE) junction cancers overexpress or have amplification of the HER2 oncogene. These patients often receive first line treatment with a combination of chemotherapy plus anti-HER2 antibody. Several other cancer types including gynecologic and urothelial cancers overexpress HER oncogene.

ENHERTU® (Trastuzumab Deruxtecan) is an Antibody-Drug Conjugate (ADC) composed of a humanized monoclonal antibody specifically targeting HER2, with the amino acid sequence similar to Trastuzumab, a cleavable tetrapeptide-based linker, and a potent cytotoxic Topoisomerase I inhibitor as the cytotoxic drug (payload). ENHERTU® has a favorable pharmacokinetic profile and the tetrapeptide-based linker is stable in the plasma and is selectively cleaved by cathepsins that are up-regulated in tumor cells. Unlike KADCYLA® (ado-Trastuzumab emtansine), another ADC targeting HER2, ENHERTU® has a higher drug-to-antibody ratio (8 versus 4), released payload easily crosses the cell membrane with resulting potent cytotoxic effect on neighboring tumor cells regardless of target expression, and the released cytotoxic agent (payload) has a short half-life, thus minimizing systemic exposure.

ENHERTU® is approved by the FDA for use in unresectable or metastatic HER2-positive breast cancer, HER2-low breast cancer, HER2-mutant non–small cell lung cancer, and locally advanced or metastatic HER2-positive gastric cancer. ENHERTU® in a Phase I trial, demonstrated clinically meaningful activity in multiple advanced solid tumors expressing HER2 oncogene.

DESTINY-PanTumor-02 is an international, open-label Phase II study conducted to evaluate the effectiveness of ENHERTU® in patients with HER2-expressing biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, or other tumors. This study involved 267 patients (N=267) across 7 different cohorts, including 6 tumor-specific cohorts (urothelial bladder, biliary tract, cervical, endometrial, ovarian, and pancreatic cancers) as well as a rare tumor cohort that included several other tumor types for which ENHERTU® is currently either not available or not being investigated (including head and neck cancers and intestinal adenocarcinoma). Patients with breast, gastric, colorectal and non-small cell lung cancers were excluded. Patients in this study had HER2-expressing (IHC 3+ or IHC 2+) locally advanced or metastatic disease that progressed after at least one systemic treatment or that had no treatment options. Among those studied 75 patients were IHC 3+ and 125 were IHC 2+ by central testing. Study patients were treated with at least one dose of ENHERTU® 5.4 mg/kg IV every 3 weeks and efficacy and safety were analyzed in all patients who received one or more doses of ENHERTU®. The Primary endpoint was investigator-assessed confirmed Objective Response Rate (ORR). Secondary endpoints included Duration of Response (DOR), Disease Control Rate, Progression Free Survival (PFS), Overall Survival, and Safety.

At data cutoff and after a median follow-up, 9.7 months, the ORR among all patients was 37.1% with a median DOR of 11.8 months. In patients with IHC 3+ expression, the ORR was 61.3% and the median DOR was 22.1 months whereas among those patients with IHC 2+ expression, the ORR was 27.2% and the median DOR was 9.8 months.

Treatment with ENHERTU resulted in the following Objective Response Rates across different tumor types:
Endometrial cancer: 57.5% for all patients, 84.6% for IHC 3+, and 47.1% for IHC 2+
Cervical cancer: 50% for all patients, 75% for IHC 3+, 40% for IHC 2+
Ovarian cancer: 45% for all patients, 63.6% for IHC 3+, 36.8% for IHC 2+
Urothelial cancer: 39% for all patients, 56.3% for IHC 3+, 35% for IHC 2+
Biliary tract cancer: 22% for all patients, 56.3% for IHC 3+, 0% for IHC 2+
Pancreatic cancer: 4% for all patients, 0% for IHC 3+, 5.3% for IHC 2+

The most common treatment-related side effects were nausea, fatigue, and cytopenias and there were no new safety signals.

It was concluded from this study results that ENHERTU® is a potential new treatment option for patients with HER2-expressing solid tumors, based on the encouraging Objective Response Rate, durable clinical benefit, and a manageable safety profile, in this heavily pretreated population. The authors added that this is the first tumor-agnostic global study of ENHERTU® in a broad range of HER2-expressing solid tumors.

Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results. Meric-Bernstam F, Makker V, Oaknin A, et al. J Clin Oncol 41, 2023 (suppl 17; abstr LBA3000)

Platelet Transfusion before Central Venous Catheter Placement in Patients with Thrombocytopenia

SUMMARY: Thrombocytopenia is a frequent finding in hospitalized patients and is one of the most common reasons for inpatient hematology consultations. Thrombocytopenia is usually defined as a platelet count of less than 150,000 per cubic millimeter, whereas severe thrombocytopenia is considered as platelet counts less than 50,000 per cubic millimeter. It is estimated that the prevalence of thrombocytopenia at admission to ICU is around 20-30% of patients, and a similar number of patients develop thrombocytopenia (from a normal platelet count) while being treated in the ICU.

Approximately 18% of hospitalized patients undergo Central Venous Catheter (CVC) placement, an invasive procedure, during admission. Central Venous Catheter facilitates simultaneous infusion of multiple medications, administration of vasoactive drugs, irritating or hypertonic solutions such as TPN, as well as hemodialysis and hemodynamic monitoring. The routine use of ultrasound guided CVC placement has greatly reduced the risk of bleeding complication. In clinical practice, platelet-transfusion thresholds range from 20,000 to 50,000 per cubic millimeter, as there is lack of good-quality evidence. It is however unclear whether the use of prophylactically transfused platelet concentrates is necessary to prevent CVC-related bleeding complications, in patients with severe thrombocytopenia.

The PACER trial is a multicenter, randomized, controlled, noninferiority study of Prophylactic Platelet Transfusion Prior to Central Venous Catheter Placement in Patients with Thrombocytopenia. This trial was conducted on hematology wards and in ICUs at 10 hospitals in the Netherlands, to evaluate whether the omission of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter increased the risk of catheter-related bleeding. This study included 373 patients (N=373) randomized in a 1:1 ratio to receive either one unit of platelet concentrate (N=188) or no platelet transfusion (N=185) before CVC placement. CVC placement was ultrasound guided, performed by an experienced operator, could be of any diameter, could be either tunneled or nontunneled, and could be placed in the internal jugular vein, subclavian vein, or femoral vein. Randomization was stratified according to the trial center and catheter type (large-bore dialysis catheter or regular catheter). Patient characteristics at the time of CVC placement were well balanced between the two trial groups. Exclusion criteria included therapeutically administered anticoagulant, a history of congenital or acquired coagulation factor deficiency or bleeding risk, or a spontaneously prolonged INR of 1.5 or more.

The Primary outcome was the occurrence of catheter-related bleeding of Grade 2-4 within 24 hours after CVC placement. Bleeding was assessed according to the Common Terminology Criteria for Adverse Events. The occurrence of bleeding and any related treatments were recorded by trained staff members at each site immediately after CVC placement, and at 1 hour and 24 hours thereafter. A key Secondary outcome was major bleeding (Grade 3-4).

Grade 2-4 catheter-related bleeding occurred in 4.8% of patients in the platelet transfusion group and in 11.9% of patients in the no-transfusion group. The absolute risk difference was 7.1%, Relative Risk was 2.45, and noninferiority of withholding platelet transfusion was not shown. The risk of Grade 3 or 4 catheter-related bleeding was lower in the platelet transfusion group compared to the no-transfusion group (2.1% versus 4.9%), with Relative Risks consistent with the Primary outcome.

The bleeding risk in the prespecified exploratory subgroup analysis, were similar to the findings of the Primary analysis. The bleeding risk among the patients being treated on the hematology ward was higher than that among patients in the ICU, and the same was true with the use of tunneled catheters as compared with nontunneled catheters. The differences in CVC-related bleeding risk was attributed to patients in the ICU more often having consumptive thrombocytopenia, whereas patients with hematologic problems in the hematology ward more often have hypoproliferative thrombocytopenia.

It was concluded from this study that in patients with severe thrombocytopenia, withholding prophylactic platelet transfusion before Central Venous Catheter placement in those with a platelet count of 10,000 to 50,000 per cubic millimeter resulted in more catheter-related bleeding events, and prophylactic platelet transfusion was associated with a lower risk of bleeding.

Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia. van Baarle FLF, van de Weerdt EK, van der Velden WJFM, et al. N Engl J Med 2023; 388:1956-1965.