Hematologic Support Research Articles

Patient outcomes after therapy with 177Lu-PSMA-617 (LuPSMA) for metastatic castrate-resistant prostate cancer (mCRPC): A tertiary center experience.

87 Background: While LuPSMA has a proven overall survival (OS) benefit in patients (pts) with mCRPC who have received prior taxane chemotherapy and androgen receptor pathway inhibitors, there is limited data on outcomes and efficacy of subsequent therapy in pts who have received LuPSMA. This study aimed to assess the clinical and treatment courses of pts with mCRPC after LuPSMA. Methods: We queried an IRB-approved prospectively maintained registry to evaluate all pts with mCRPC who received standard-of-care LuPSMA at our institution between June 2022 and July 2023. Clinical data pertaining to LuPSMA therapy as well as subsequent treatments were extracted from the medical record, including type and number of subsequent systemic therapies, reason for treatment cessation, hematologic support, and PSA response to subsequent therapy. PSA-50 was defined as a ≥50% decrease in PSA on therapy. Hematologic adverse events to therapies after LuPSMA were recorded and graded per CTCAEv5.0. Results: A total of 96 patients were evaluated; median age was 72 years (range 52-87), and median follow-up was 10 months. 18 pts completed all 6 cycles, 35 discontinued prior to cycle 6 of LuPSMA due to progressive disease, 10 died mid-treatment, and 33 were midway through treatment; median number of cycles received for all pts was 4 (range 1-6). None of the 18 who completed all 6 cycles had yet transitioned to a next line therapy. Of the 35 who discontinued LuPSMA, 17 transitioned to hospice due to disease progression, 15 initiated a subsequent line of therapy, and 3 had a treatment break. Median overall survival was 13 months in the entire cohort. Of the 15 receiving another line of therapy, 11 received cabazitaxel ± carboplatin/cisplatin, 1 received carboplatin with cisplatin substituted during carboplatin shortage, and 4 received other non-chemotherapy regimens; a PSA-50 response to subsequent therapy was seen in 4 patients (27%), all of whom received cabazitaxel ± carboplatin/cisplatin. Of the 12 pts who received chemotherapy, the median number of cycles received was 3 (range 1-7); 4 pts (33%) had grade ≥3 anemia, 2 (17%) had grade ≥3 thrombocytopenia and 7 pts (47%) required platelet growth factor support or transfusion of blood products. Conclusions: 47% of pts discontinuing LuPSMA transitioned to hospice due to disease progression while 44% proceeded to a subsequent line of therapy, the majority of whom received cabazitaxel. Outcomes to subsequent therapy were generally poor, with a 27% PSA-50 response rate. This initial experience may be biased by number of patients with limited standard of care options at the time of FDA approval of LuPSMA and could improve with better patient selection. However, this also highlights the continued need to develop novel therapeutic strategies for CRPC pts post-LuPSMA.

Hematologic Support in HIV Patients: Blood Transfusion Strategies and Immunological Considerations

HIV infection presents multifaceted challenges, particularly in managing hematologic complications that significantly impact patient well-being and prognosis. Hematologic manifestations such as anemia, thrombocytopenia, and coagulopathies are prevalent in individuals living with HIV, necessitating meticulous attention and specialized care. Among the array of interventions, blood transfusions play a pivotal role in addressing these hematologic complications. However, the complexities surrounding blood transfusion strategies in the context of HIV extend beyond mere hematologic support and delve into intricate immunological considerations. This paper aims to elucidate the nuanced landscape of hematologic support in HIV patients, focusing specifically on blood transfusion strategies and their immunological implications. The review encompasses an in-depth analysis of hematologic abnormalities commonly encountered in HIV, exploring the prevalence, etiology, and clinical impact of anemia, thrombocytopenia, and coagulopathies. Additionally, it examines the indications, safety measures, and challenges associated with blood transfusion therapy in this population. Furthermore, the paper delineates the intricate interplay between blood transfusions and the immunological milieu of HIV-infected individuals. It explores the immunomodulatory effects of transfusions, potential immune activation, and the impact on disease progression, while also addressing concerns regarding alloimmunization and the modulation of immune responses posttransfusion. By synthesizing current evidence and insights, this paper delineates the clinical outcomes, challenges, and controversies surrounding blood transfusion strategies in HIV care. It underscores the need for optimized transfusion practices tailored to the unique immunological landscape of HIV patients and highlights avenues for future research and advancements in clinical practice. In conclusion, this paper serves as a comprehensive resource elucidating hematologic support through blood transfusion strategies in HIV patients, providing a foundation for informed decision-making and paving the way for enhanced care paradigms in the management of hematologic complications in HIV. Keywords: Hematologic Support, HIV, Patients and Blood Transfusion

To bleed or not to bleed? Case series and discussion of haemorrhage risk with enzymatic debridement in burn injuries.

Surgical burn excision (along with skin grafting) carries the risk of blood loss. The use of enzymatic debridement agents such as Nexobrid® has gained increased popularity as an alternative to surgical debridement in the management of burns with its reported benefits of selective burn debridement, minimising blood loss and potentially reducing the need for skin grafting. However, there is limited evidence regarding its effects on bleeding. Currently, the manufacturer declares there is no evidence for increased risk of localised bleeding and its systemic effects upon coagulation are less clear. We present two clinical cases demonstrating the possible effects of Nexobrid® on coagulation and bleeding at the debridement site. Comparisons are drawn with the manufacturers' guidance as well as evaluating the current recommendations of its use. Nexobrid® is a novel therapy and there are few adverse effects reported in the literature. The basis of its appeal is the reduced blood loss at the debridement site and the selectivity it possesses in preserving healthy dermis. However, our cases have demonstrated that haemorrhage can occur and that those using Nexobrid® should be mindful of the potential bleeding risk from varicosities within the burn wound. We have also illustrated that Nexobrid® can be used in patients with pre-existing clotting disorders without requiring the use of blood products. However, we emphasise the importance of haematological support for its safe administration. Nexobrid®, a debriding agent that contains enzymes, has been developed as an alternative to surgery which for most surgeons is the traditional method of removing dead tissue following a burn injury. The active agent is bromelain and this is derived from the stems of pineapples. This novel treatment is increasingly being used in the management of middle to deep skin thickness burns and it seems to have a number of benefits such as reducing blood loss, reducing the need for skin grafting as well as being able to treat burns in certain areas of the body that would be technically challenging to remove in the standard fashion. It simply targets the dead tissue leaving viable remnants of the skin that would hopefully allow healing to occur without the need for surgical intervention. Being a relatively new concept, current evidence regarding the safety and value of Nexobrid® continues to develop. In 2020, an agreement guideline outlining best practice with the use of Nexobrid® was published. In this statement, it was advised that caution should be taken when using Nexobrid® in patients who have blood clotting disturbances as this could increase the likelihood of bleeding. However, they did not mention that excessive bleeding can potentially occur with this treatment.We present two clinical cases demonstrating the possible effects of Nexobrid® on the clotting system and bleeding at the application site. Comparisons are drawn with the manufacturers' guidance as well as assessing the current recommendations of its use. We illustrate that Nexobrid® can be safely used in patients with pre-existing clotting disturbances if the correct procedures are performed. We also highlight the potential complication of excessive bleeding if Nexobrid® is used in patients who have co-existing enlarged surface veins along with their burn injury. We feel the guidance should be updated to reflect these findings.

Rodent Model for Orthotopic Implantation of Engineered Liver Devices.

This study presents a novel surgical model developed to provide hematological support for implanted cellularized devices augmenting or replacing liver tissue function. Advances in bioengineering provide tools and materials to create living tissue replacements designed to restore that lost to disease, trauma, or congenital deformity. Such substitutes are often assembled and matured in vitro and need an immediate blood supply upon implantation, necessitating the development of supporting protocols. Animal translational models are required for continued development of engineered structures before clinical implementation, with rodent models often playing an essential early role. Our long-term goal has been generation of living tissue to provide liver function, utilizing advances in additive manufacturing technology to create 3D structures with intrinsic micron to millimeter scale channels modeled on natural vasculature. The surgical protocol developed enables testing various design iterations in vivo by anastomosis to the host rat vasculature. Lobation of rodent liver facilitates partial hepatectomy and repurposing the remaining vasculature to support implanted engineered tissue. Removal of the left lateral lobe exposes the underlying hepatic vasculature and can create space for a device. A shunt is created from the left portal vein to the left hepatic vein by cannulating each with separate silicone tubing. The device is then integrated into the shunt by connecting its inflow and outflow ports to the tubing and reestablishing blood flow. Sustained anticoagulation is maintained with an implanted osmotic pump. In our studies, animals were freely mobile after implantation; devices remained patent while maintaining blood flow through their millifluidic channels. This vascular anastomosis model has been greatly refined during the process of performing over 200 implantation procedures. We anticipate that the model described herein will find utility in developing preclinical translational protocols for evaluation of engineered liver tissue. Impact statement Tissue and organ transplantation are often the best clinically effective treatments for a variety of human ailments. However, the availability of suitable donor organs remains a critical problem. Advances in biotechnology hold potential in alleviating shortages, yet further work is required to surgically integrate large engineered tissues to host vasculature. Improved animal models such as the one described are valuable tools to support continued development and evaluation of novel therapies.

Safety, tolerability, and effectiveness of anticoagulation and antiplatelet therapy in hereditary hemorrhagic telangiectasia

BackgroundAntithrombotic therapy (anticoagulation and antiplatelet therapy) is frequently needed in patients with hereditary hemorrhagic telangiectasia (HHT); however, data describing and guiding its use are very limited. ObjectivesTo investigate the safety, tolerability, and effectiveness of antithrombotic therapy in HHT in a cohort large enough to compare agents, evaluate for baseline predictors of premature discontinuation, and evaluate hematologic support requirements and healthcare utilization before and after antithrombitc therapy initiation. MethodsWe performed a multicenter observational cohort study characterizing the outcomes of antithrombic therapy in adults with HHT. ResultsA total of 119 patients with HHT with 187 discrete antithrombotic therapy episodes were included. Of these, 59 patients (50%) dose-reduced and/or prematurely discontinued therapy (including 52 patients [44%] who discontinued) due to worsened bleeding complications. Initiation at reduced dose intensity had a similar premature discontinuation rate (49%) as initiation at standard dose intensity (43%). In a multivariable logistic model, a history of gastrointestinal bleeding was associated with 3.25-fold odds of discontinuation (p = .001). Hemoglobin was significantly lower (10.8 g/dL vs 12.2 g/dL, p < .001), and the need for hematologic support (intravenous iron and/or red blood cell transfusion) was significantly higher (29 patients vs 12 patients, p = .004) in the 3 months after antithrombotic therapy initiation vs the 3 months before; emergency department visits and hospital admissions due to bleeding also increased. The rates of dose-reduction and/or premature discontinuation were similar regardless of the anticoagulant class (warfarin, 46%; heparin-based, 48%; direct oral anticoagulants, 44%) or with multiple simultaneous agents (44%) but were slightly lower with single-agent antiplatelet therapy (37%). Thromboembolism despite receiving antithrombotic therapy was common (18 patients, 15%) with varying outcomes. ConclusionAntithrombotic therapy is challenging in HHT, resulting in objectively higher morbidity and health care utilization from worsened bleeding. Discontinuation rates approached 50% regardless of the dose intensity at initiation or type of antithrombotic agent used and were higher in patients with a gastrointestinal bleeding history.

Systemic bevacizumab as salvage therapy for persistent severe bleeding and anemia in heyde syndrome following aortic valve replacement.

Heyde syndrome is characterized by the co-occurrence of aortic stenosis and bleeding gastrointestinal angiodysplasias, often with acquired von Willebrand syndrome. Current management for bleeding includes hematologic support with red cell transfusion and intravenous iron and correction of aortic stenosis with valve replacement. However, persistent Heyde syndrome after valve replacement occurs in a significant minority of cases, and there is no accepted therapy for these patients. Given that the pathophysiology of angiodysplasia formation in Heyde syndrome involves dysregulated angiogenesis, targeting angiogenesis may be an effective therapeutic option. We describe two cases of persistent Heyde syndrome with severe bleeding and anemia in patients following aortic valve replacement who were treated with systemic bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor. In both cases, treatment was successful, with resolution of bleeding, liberation from hematologic support, and normalization of hemoglobin. In addition to responding to therapy, neither patient had treatment-related adverse events (and both had recurrent anemia upon treatment discontinuation, further evidence of the therapeutic impact of bevacizumab). Additional investigation into the use of systemic antiangiogenic therapy for treatment of Heyde syndrome is warranted.

Systemic Antiangiogenic Therapies for Bleeding in Hereditary Hemorrhagic Telangiectasia: A Practical, Evidence-Based Guide for Clinicians.

Management of bleeding in hereditary hemorrhagic telangiectasia (HHT), the second most common hereditary bleeding disorder in the world, is currently undergoing a paradigm shift. Disease-modifying antiangiogenic therapies capable of achieving durable hemostasis via inducing telangiectasia regression have emerged as a highly effective and safe modality to treat epistaxis and gastrointestinal bleeding in HHT. While evidence to date is incomplete and additional studies are ongoing, patients presently in need are being treated with antiangiogenic agents off-label. Intravenous bevacizumab, oral pazopanib, and oral thalidomide are the three targeted primary angiogenesis inhibitors, with multiple studies describing both reassuring safety and impressive effectiveness in the treatment of moderate-to-severe HHT-associated bleeding. However, at present there is a paucity of guidance in the literature, including the published HHT guidelines, addressing the practical aspects of antiangiogenic therapy for HHT in clinical practice. This review article and practical evidence-based guide aims to fill this unaddressed need, synthesizing published data on the use of antiangiogenic agents in HHT, relevant data for their use outside of HHT, and expert guidance where evidence is lacking. After a brief review of principles of bleeding therapy in HHT, guidance on hematologic support with iron and blood products, and alternatives to antiangiogenic therapy, this article examines each of the aforementioned antiangiogenic agents in detail, including patient selection, initiation, monitoring, toxicity management, and discontinuation. With proper, educated use of antiangiogenic therapies in HHT, patients with even the most severe bleeding manifestations can achieve durable hemostasis with minimal side-effects, dramatically improving health-related quality of life and potentially altering the disease course.

Successful outcome of pregnancy with aplastic anaemia: A case report

Pregnancy in aplastic anaemia is rare and it may exacerbate bone marrow depression and cause deterioration, which can be life threatening for both mother and child. It poses a great challengeto the haematologist as well as obstetrician as the management of such cases challenges their skills in deciding the best treatment option for the patient. The first report of Aplastic anemia in Pregnancy was publised by Ehrlich in 1888. Haemorrhage and sepsis due to pancytopenia are the mainfactors responsible formortality in pregnant women with aplastic anemia. Treatment options are erythrocytes and platelet transfusions and immuno suppressive therapy. Immunosuppressive agents or hemopoietic stem cell transplantation are contraindicated during pregnancy. There is no universal agreement about the optimal treatment regime for this disorder in pregnancy, and supportive therapy remains the mainstay of therapy. The present case report describes our experience with a patient with aplastic anaemia, who was managed with intensive haematological support leading to delivery of a healthy baby.

Hereditary Spherocytosis in PregnancyA Case Report

Hereditary Spherocytosis (HS) is the most common inherited red cell membrane disorder included under intracorpuscular defect. HS has both autosomal dominant and autosomal recessive inheritance. The disease may be mild, moderate or severe and requires a multidisciplinary approach for its management during pregnancy. Hereby, authors discusses a case of a 30-year-old female G2P1L1 at 34 weeks+4 days presented with anaemia not responding to iron therapy since first trimester. Peripheral blood smear revealed red blood cell’s were normocytic and normochromic. Spherocytes were seen with mild polychromatophilia and diagnosed as a case of HS and its management was done with haematological support.

Systemic bevacizumab to facilitate anticoagulation in antiphospholipid syndrome and bleeding gastrointestinal angiodysplasia.

Bleeding gastrointestinal angiodysplasia may occur in patients with vasculitis and can be challenging to treat. We describe the novel use of bevacizumab therapy to treat bleeding gastrointestinal angiodysplasia and severe anemia in a patient with eosinophilic granulomatosis with angiitis complicated by antiphospholipid antibody syndrome requiring indefinite warfarin therapy. Studies confirmed multiple bleeding jejunal angiodysplasias unamenable to endoscopic intervention, and the patient required ongoing support with iron infusions and blood transfusions to maintain a minimally acceptable hemoglobin. Given the severe anemia, need for continued, indefinite antiplatelet and anticoagulation therapy, and failure of standard treatment approaches, the patient was initiated on systemic bevacizumab therapy, on the basis of prior documented success of bevacizumab to manage gastrointestinal telangiectasias in patients with hereditary hemorrhagic telangiectasia. Bevacizumab was highly effective, with rapid resolution of bleeding, normalization of hemoglobin, liberation from hematologic support and no adverse events, including no thromboembolic events. Vascular endothelial growth factor (VEGF-A) rose paradoxically after initiation of bevacizumab and normalized after its discontinuation. Given these findings, use of systemic bevacizumab to manage bleeding angiodysplasia in patients with acquired vascular disorders merits further study.

"A JAR FULL OF PINK FROTH": AN ATYPICAL CASE OF AMNIOTIC FLUID EMBOLISM AFTER A DILATION AND CURETTAGE AT SEVEN WEEKS GESTATION

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Amniotic fluid embolism (AFE) is one of the leading causes of death during pregnancy in developed countries. It is an uncommon, life-threatening complication often associated with advanced maternal age, multi-parity, and placental rupture. It is extremely rare in the first trimester, as the small amount of amniotic fluid and fetal cells are unlikely to breach the maternal circulation. Here, we present an atypical case of AFE occurring at 7 weeks gestation. CASE PRESENTATION: The patient is a healthy 29-year-old nulliparous woman who developed acute onset chest pain, dyspnea, and productive cough with pink frothy sputum within 30 minutes of dilation and curettage (D&C), which she underwent after spontaneous abortion at 7 weeks gestation. Her symptoms were accompanied by acute hypoxemic respiratory failure, shock, and coagulopathy. She did not have any rash or skin changes. Computed tomography angiography of the chest was negative for pulmonary embolism but showed bilateral patchy opacities in all lobes. Transthoracic echocardiogram showed normal biventricular and valvular function. The patient required supportive care with as many as three vasopressors and Bilevel Positive Airway Pressure at 100% FiO2 and left the intensive care unit after approximately 72 hours. She was discharged home after 7 days, by which time she had fully recovered. DISCUSSION: Amniotic fluid embolism is a diagnosis of exclusion, without rapid and accurate diagnostic options available. For this reason, early and atypical cases of AFE are likely underreported. In AFE, the normal physiology is altered due to increased immunological response upon physical breach of amniotic fluid into maternal circulation, releasing procoagulant and vasoactive mediators to cause anaphylactic reaction to the fetal antigen (1). Hence, the imbalance can cause multi-organ failure, exhibited through a classic triad of hypotension, hypoxia, and coagulopathy that were demonstrated in our case without clear etiology for shock and respiratory decompensation. Management is focused on adequate cardiovascular, pulmonary, and hematologic support. Because no cases of recurrence have been reported, current data suggests successful subsequent pregnancies (2). CONCLUSIONS: Our case highlights a patient at 7 weeks gestation with unexplained shock, respiratory failure, and coagulopathy less than 1-hour status post D&C, and may represent the earliest documented case of AFE. Diagnosis of AFE is based upon clinical findings and symptoms, with treatment focused on providing adequate hemodynamic support. Due to limited understanding of its pathophysiology, an emphasis on early diagnosis and treatment is critical to prevent significant mortality. REFERENCE #1: Society for Maternal-Fetal Medicine (SMFM). Electronic address: pubs@smfm.org, Pacheco LD, Saade G, Hankins GD, Clark SL. Amniotic fluid embolism: diagnosis and management. Am J Obstet Gynecol. 2016 Aug;215(2):B16-24. doi: 10.1016/j.ajog.2016.03.012. Epub 2016 Mar 14. PMID: 26987420. REFERENCE #2: 177: The risk of amniotic fluid embolism reoccurrence in subsequent pregnancy, Irene Stafford, Presley S. Parkes, Amir Moaddab, Miranda Klassen, Steven L. Clark, Michael A. Belfort, Gary A. Dildy, American Journal of Obstetrics and Gynecology, Volume 218, Issue 1, Supplement, https://doi.org/10.1016/j.ajog.2017.10.054. DISCLOSURES: No relevant relationships by Wahaaj Khan, source=Web Response No relevant relationships by Do Yun Kim, source=Web Response No relevant relationships by Andrew Toscano, source=Web Response

Sclerotherapy Versus Cautery/Laser Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia.

Surgical interventions for epistaxis management in hereditary hemorrhagic telangiectasia (HHT) demonstrate short-term success and require repeated procedures for disease control. Although electrocautery and/or laser photocoagulation (C ± L) are most frequently performed, sodium tetradecyl sclerotherapy (STS) is emerging as a promising newer treatment. We hypothesized that in a 24-month time period, STS would require fewer treatments than C ± L to maintain epistaxis severity within the mild range. Retrospective study. We retrospectively assessed 67 patients with HHT with moderate and severe epistaxis that were treated periodically with C ± L (34 patients) versus STS (33 patients). The primary outcome was the number of procedures needed to maintain the epistaxis severity score (ESS) as mild. Secondary outcomes assessed for differences in postoperative complications, hemoglobin levels, iron stores, hematologic support, and quality-of-life (QoL) scores. To maintain ESS in the mild range, 1.6 STS procedures (range, 1-4) were performed versus 3.6 C ± L procedures (range, 1-8) (P=.003). Significant postoperative differences included reduction in nasal crusting (3% vs. 32%, P=.001), foul odor (3% vs. 35%, P < .001), and septal perforation (3% vs. 29%, P=.006) after STS. There were no significant differences between the two treatments in hemoglobin levels, iron stores, hematologic support, or QoL scores. STS is able to attain satisfactory epistaxis control with significantly fewer procedures and lower postoperative complications than C ± L. STS should be considered as the initial surgical intervention for epistaxis in patients with HHT. 4 Laryngoscope, 132:920-925, 2022.

Triple procedure in blood-stained cornea of a hemophilia patient

A 16-year-old male Type A hemophiliac patient has been reported with complaints of defective vision in the right eye (OD), following ocular trauma 9 months back for which he took treatment outside. On examination, he had blood staining of cornea and cataract in his right eye. His vision was perception of light + and projection of rays intact. After hematologist opinion, under peribulbar anesthesia, he underwent penetrating keratoplasty with pupillary membranectomy and cataractous lens removal with posterior chamber intraocular lens implantation under the cover of Factor VIII (antihemophilic factor). On day 21, the best-corrected visual acuity in OD was 6/6P. This case report emphasizes the fact that hemophiliac patients can be operated safely with appropriate hematological support.

The Efficiency of Substitutive Treatment with Moroctocog Alfa in Managing Hemostasis in Patients with Hemophilia A Without Inhibitors With Total Knee Arthroplasties

Hemophilia A is a hereditary coagulopathy caused by the deficiency of the coagulation factor VIII, whose main complication consists in disabling arthropathy. The most often affected joint is the one of the knee, due to which this article aims at presenting, on one hand, the role of continuous substitutive prophylactic treatment in preventing the onset of this complication and, on the other hand, the current view of orthopedic surgery in managing the above-mentioned complication. The continuous prophylactic treatment represents the best therapeutic conduct in preventing the onset of hemophilic arthropathy, yet this aspect is limited by two important factors: inappropriate medical support, dependence on the social and economic level of every country and inappropriate adherence of the patient to this thorough treatment, which represents a challenge for a life with no bleeding. Under the circumstances imposed by an insufficient substitutive treatment or by a deficient adherence of the patient to this, recurrent hemarthrosis shall lead to cartilage destruction and synovial hypertrophy (synovitis), which will impose, in time, total endoprosthesis in order to re-establish the motor function and to improve the life quality of the hemophilic patient. The surgery of the hemophilic patient is associated with an increased risk of hemorrhage and infection and it is practiced only with substitutive hematologic support. The key to the best results is the existence of a multidisciplinary experienced team, including an orthopedist, hematologist, physical therapist.

Clinicopathological characteristics of disseminated carcinomatosis of the bone marrow in breast cancer patients.

Disseminated carcinomatosis of the bone marrow (DCBM) is characterized by diffuse infiltrative growth of tumor cells in the bone marrow and is associated with systemic hematological disorders. Bone marrow metastases from breast cancer are not rare, and they may lead to serious life-threatening conditions when there is an associated hematological disorder. Therefore, DCBM necessitates a definitive diagnosis and prompt systemic therapy. We herein present 4 such cases and a review of the previous relevant literature. Bone marrow biopsy is an effective method for diagnosing DCBM, and it may also be useful for selecting the optimal therapy. The malignant cells in the bone marrow biopsy specimens from all 4 patients were negative for progesterone receptor expression, and in 1 case, human epidermal growth factor receptor 2/neu expression was discordant between the primary tumor and the bone marrow metastases. Patients with DCBM often require granulocyte colony-stimulating factor and/or blood transfusions due to a DCBM-related hematological disorder. Although systemic chemotherapy for DCBM may temporarily exacerbate the need for hematological support, systemic chemotherapy may be effective for DCBM in breast cancer patients. In our experience, endocrine therapy has also been proven effective for DCBM. The aim of the present study was to review the clinical characteristics and the treatments used in 4 breast cancer patients with DCBM.

Management of Hematochezia in Blue Rubber Bleb Nevus Syndrome

Intro: Blue Rubber Bleb Nevus syndrome (BRBNS) is a rare disease that is characterized by mucocutaneous venous malformations that most commonly affect the skin and gastrointestinal (GI) tract. We present a case report describing the therapeutic challenges of managing a GI bleed secondary to BRBNS.Figure: Numerous blue rubbery papules located on the patient's a) right thigh b) left thigh and c) right foot.Figure: Smaller blebs scattered throughout the colon.Figure: Colonoscopy showing a large bleb in the ascending colon.Case Report: A 41-year-old female patient with a history of BRBNS presented to our clinic with a complaint of spontaneous rectal bleeding, requiring her to wear a pad everyday for the past 5 months. Physical exam was notable for scattered blue nodules on her thighs and right foot (figure 1). Labs were significant for a hemoglobin of 10.4 g/dL, platelets of 118 K/uL, fibrinogen of < 80 mg/dL. On colonoscopy, a dozen blue rubber blebs were located throughout the colon (figure 2). The most erythematous and prominent bleb, which measured 1.5 cm, was believed to have been the culprit of her recurrent rectal bleeding and anemia, and thus was the target for intervention (figure 3). The lesion was suctioned into the banding apparatus, but the attempt to deploy a band merely resulted in spontaneous albeit self-limited bleeding. While lavaging the decompressed bleb, a second neighboring bleb began to actively bleed. Injection with both 6 cc of epinephrine and 2 mL of butyl-2-cyanoacrylate glue slowed but did not cease the hemorrhage. Band ligation was then employed on this second bleb, and hemostasis was achieved. Because of the risk of underlying DIC, the patient received 10 units of cryoprecipitate. No further bleeding was reported at a ten day follow-up. Discussion: As demonstrated, successful banding may be difficult giving the large size of the blebs. Injecting glue into the bleb did not result in hemostasis, and still required additional banding to stop the active bleed. Although it is not typical, this technique of injecting glue may have helped change the consistency of the lesion, creating solidification and making banding more successful. In patients with chronic DIC, as in our case, periprocedural hematologic support with platelets and cryoprecipitate may help in the setting of active bleeding. Surgery, as well as the use of interferon, octreotide, or sirolimus may be considered in cases of refractory bleeding. Conclusion: Management of BRBNS is challenging because there is no cure or treatment guidelines and experience is limited to case reports. More studies are needed to elucidate the most effective hemostasis strategy for bleeding lesions in BRBNS.

Anaemia in Cancer Patients Undergoing Radiotherapy and Chemotherapy at the National Hospital, Abuja

Anaemia is one of the predisposing factors to poor patient outcome in cancer treatment. More than 50% of cancer patients will receive either Radiotherapy or Chemotherapy or both in the course of their treatment. It has been difficult to establish global or National benchmark on the baseline haemoglobin of patients selected for cancer therapy at different stages of the tumours. Various centers use different levels but there is a need to establish a national cut-off point. Establishing a uniform benchmark will inform a global best practice and increase the patient’s outcome and quality of life. The acceptable value of anaemia varies from centre to centre but Hb level of 10 g/dL in both male and female are usually acceptable in most Radiation Oncology Centers in Nigerian Hospitals. Haemoglobin level of 10 g/dL is a borderline value and administration of Radiotherapy or Chemotherapeutic agents however without adequate hematological support may tilt the patient into clinical anaemia. This prospective study was done to determine the pattern of anaemia in cancer patients undergoing Radiotherapy and Chemotherapy in Nigeria using 201 cancer patients enrolled in National Hospital Abuja with histopathologically confirmed malignancies (solid cancers). The prevalence of anaemia in the study was 63%. The impact of Chemotherapy on Hb level was more significant than in other treatment arms, hence Chemotherapy – 9.60-10.62 g/dL, Radiotherapy 11.52-12.13 g/dL, and Chemoradiation 10.98-11.36 g/dL. The HB level continually decreased in all arms of treatment. We recommend a benchmark of 11 g/dL minimum for any patient being selected for Radiotherapy, Chemotherapy and Chemoradiation in Nigeria.

A Phase II Study of Pomalidomide, Daily Low Dose Oral Cyclophosphamide, and Dexamethasone in Relapsed/Refractory Multiple Myeloma

Relapsed/refractory multiple myeloma patients treated with pomalidomide and dexamethasone have an overall response rate (ORR) of ∼30% and median progression-free survival (PFS) of 4–5 months. Previ...

Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation.

In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI) and partial-body irradiation (PBI) to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS) and need hematologic support (i.e., mostly TBI victims). To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18) were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI) or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI). More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6) and PBI (n = 12), for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.

Abstract B98: Final results of a randomized phase Ib study of fractionated 90Y-clivatuzumab tetraxetan in patients with metastatic pancreatic cancer having at least two prior therapies

Abstract Background: Prior clinical studies in the first and second line setting showed radioimmunotherapy (RAIT) is a promising therapy for pancreatic cancer that avoids the side effects of further chemotherapy. This multicenter study evaluated the contribution of low radiosensitizing doses of gemcitabine (GEM) to fractionated doses of 90Y-clivatuzumab tetraxetan in patients with metastatic pancreatic ductal cancer after having received at least 2 prior systemic therapies. Methods: Fifty-eight patients (33 males, 25 females; median age 63.5 years), 1.6 median years from diagnosis and with a median of 3 (2-7) prior treatments, were randomized to Arm A (N=29, 4-week cycles: 200 mg/m2 GEM, weekly, combined with 6.5 mCi/m2 90Y-clivatuzumab tetraxetan, weekly the last 3 weeks) or Arm B (N=29, 3-week cycles: 6.5 mCi/m2 90Y-clivatuzumab tetraxetan alone, once-weekly), repeating cycles after 4-week delays. Safety and efficacy were evaluated. Results: None of the patients had infusion reactions, and as expected, cytopenias (predominantly thrombocytopenia) were the only significant toxicities, but mostly transient and manageable with infrequent hematologic support and little evidence of increased infection or bleeding. Patients terminated treatment cycles due to disease progression or clinical deterioration, not treatment toxicity. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ≥1 full treatment cycle and thus were evaluable for efficacy, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including 7 (6 Arm A, 1 Arm B; 12%) given 3-7 cycles. Two patients in Arm A had PRs by RECIST criteria. Karnofsky performance status (90-100 v 70-80), number of prior therapies, and tumor burden estimates (summed length of index lesions, serum CA 19-9 levels) correlated with overall survival (OS), but appear balanced between arms. Kaplan-Meier median OS was 3.9 months (1.0-16.7) in Arm A v 2.8 months (0.9-9.4) in Arm B (hazard ratio 0.54, 95% CI: 0.27-0.87; P=0.020, log-rank). The median OS for Arm A v Arm B increased to 7.9 v 3.4 months with multiple cycles (P= 0.004) and 3 patients in Arm A still being observed (11 – 17 months). Conclusions: This randomized trial demonstrated the feasibility of performing clinical studies in metastatic pancreatic cancer patients after having at least 2 prior therapies (3rd line and beyond). With significant survival advantage and favorable safety profile, fractionated RAIT with 90Y-clivatuzumab tetraxetan and low-dose GEM appears promising in this difficult population, supporting Phase 3 studies of this combination now being initiated. Citation Format: Vincent J. Picozzi, Ramesh K. Ramanathan, Maeve A. Lowery, Allyson J. Ocean, Edith P. Mitchell, Bert H. O'Neil, Michael J. Guarino, Paul R. Conkling, Steven J. Cohen, Nathan Bahary, Richard C. Frank, Tomislav Dragovich, Benjamin B. Bridges, Marie Lee, Ronald L. Korn, Neeta Pandit-Taskar, Stanley J. Goldsmith, Charles M. Intenzo, Arif Sheikh, Timothy C. Manzone, Michael L. Miller, Michael Yu, Judith M. Joyce, Edward B. Strauss, Susan Passalaqua, Ronald V. Dorn, III, Michael J. Anderson, Michael Holt, Fadi S. Braiteh, Fa-Chyi Lee, Thomas E. Gribbin, Donald A. Richards, Alexander N. Starodub, Wegener A. William, Eileen M. O'Reilly, Daniel D. Von Hoff, David M. Goldenberg. Final results of a randomized phase Ib study of fractionated 90Y-clivatuzumab tetraxetan in patients with metastatic pancreatic cancer having at least two prior therapies. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B98.