Prognostic Scoring Systems in Allogeneic Hematopoietic Stem Cell Transplantation: Where Do We Stand?

Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment for many hematologic disorders. Maximizing the benefit of transplantation for disease control while minimizing the risk for associated complications remains the field's leading challenge. This challenge has prompted the development of multiple prognostic scoring systems over the last 2 decades. Prognostic scores can be used for informed decision making, better patient counseling, design of interventional trials, and analysis of prospective and retrospective data. They are also helpful in treatment allocation and personalization according to predicted risk. A better understanding of the molecular and cytogenetic features of the disease, along with the advent of novel therapies, has increased the need for reliable prognostication of which patients will benefit most from transplantation. Here we review the clinical role of the prognostic systems currently in clinical use, examining both their strengths and their limitations.

The Prognostic Significance of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Patients With Multiple Myeloma.

OBJECT: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are simple, inexpensive prognostic markers for various conditions. The objective of this study was to determine the prognostic significance of NLR and PLR in patients with multiple myeloma (MM) in terms of survival. METHOD: A retrospective chart review study was conducted for 175 patients who met the criterion of diagnosis for MM between January 2004 and September 2014. RESULT: The median age of diagnosis was 69 years. Patients were divided into high and low NLR and PLR groups according to cutoff points from the receiver operating characteristic curve (2.78 and 155.58, respectively). The high NLR and PLR groups were associated with lower albumin level and higher staging. The high NLR group experienced inferior median survival compared with the low NLR group (37 vs. 66 months; log-rank P-value 0.005). However, there was no significant difference in median survival between the high and low PLR groups (45 vs. 62 months; P = 0.077). Multivariate analysis demonstrated that NLR is an independent predictor for OS of MM (HR 2.892; P = 0.009). CONCLUSION: We conclude that NLR is an independent prognostic factor for OS in MM.

An 80-Year-Old Man with Ischemic Heart Disease Who Developed Thrombotic Thrombocytopenic Purpura Following Treatment with Ticagrelor.

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is associated with widespread microvascular thrombosis, low platelet count, and hemolysis. Ticagrelor is a relatively new agent which functions as a reversible inhibitor of the P2Y12 receptor working to prevent platelet aggregation and is used with or without aspirin in patients with acute coronary syndrome to reduce the risk of myocardial infarction and stroke. We describe the case of an 80-year-old man with ischemic heart disease who developed this rare and potentially fatal adverse reaction known as TTP following treatment with ticagrelor. CASE REPORT We report the case of an 80-year-old man who presented with an acute change in mental status 4 months after initiating ticagrelor following percutaneous coronary intervention. Laboratory testing on presentation revealed evidence of microangiopathic hemolytic anemia, thrombocytopenia, and elevated creatinine levels, suggestive of acute renal failure. The combination of his clinical symptoms and laboratory findings were concerning for TTP, likely secondary to ticagrelor use. The patient was treated with therapeutic plasma exchange, systemic steroids, and hemodialysis, which led to resolution of the hemolysis and recovery of renal function. CONCLUSIONS Although the association between ticagrelor and TTP is rare, early recognition of this life-threatening complication is essential to decrease morbidity and mortality associated with TTP. Since ticagrelor is now more commonly used, it is important that clinicians be aware of this complication.

Pyoderma gangrenosum of the breast ­ Case report / Emlo pyoderma gangraenosuma - Esetbemutatás

Pyoderma gangrenosum (PG) of the breast is a rare, ulcerative disease of rapid onset normally associated with systemic disorders and triggered by surgery or trauma. Early diagnosis and appropriate treatment of this disease pose a real challenge. We present a case of a PG of the breast in a patient with associated diabetes mellitus, with minor triggering injury. Our patient's condition was diagnosed and treated as an infected breast ulcer; after getting the correct diagnosis we treated her with systemic steroids and finally (at the patient's request) with breast ablation.

[Case report of a "benign" iatrogen duodenal diverticular perforation]. / "Jótékony" iatrogén duodenalis diverticulum perforatio esete.

The authors present a case of a 78-year-old female patient who was initially examined at the cardiology department for consideration of pacemaker implantation. An upper GI endoscopy was performed due to anemia and melena and a large duodenal diverticulum was identified. Consequently, signs of acute abdomen developed and further examinations confirmed diverticular perforation. As an emergency surgical resection of the diverticulum was performed and the patients recovered uneventfully. In this case report the authors discuss the management of the above condition as well as literature review is performed.

Falsely positive heparin-induced thrombocytopenia antibody testing in severe hyperbilirubinemia.

Heparin-induced thrombocytopenia (HIT) is a life-threatening pathologic reaction to heparin-based products. Diagnosis of this condition can be confounded by other comorbidities or by acute illness-oftentimes presenting challenging clinical dilemmas, particularly in critically ill patients. A 67-year-old woman was admitted with liver failure and severe hyperbilirubinemia. She developed thrombocytopenia after prophylactic heparin exposure. Subsequent quantitative latex immunoturbidimetric assay (LIA) HIT antibody testing was intermediately positive. Confirmatory serotonin release assay testing subsequently returned negative. Platelet factor4-dependent P-selectin expression assay also returned negative, suggesting false positivity of the initial LIA tests. Concern was raised that hyperbilirubinemia (total bilirubin, 55.5 mg/dL) interfered with the original assay. Further testing with a separate HIT ELISA assay, which includes multiple washes and dilutions of the serum in order to effectively remove bilirubin, returned negative. Medical providers must consider the possibility of false-positive LIA testing when evaluating for HIT in the setting of severe hyperbilirubinemia.

The neuropathic itch: Don't scratch your head too hard!

Postherpetic complications can sometimes result in significant debility. A multidisciplinary approach is crucial in deciding the appropriate treatment strategy in these patients.

Secondary Plasma Cell Leukemia: A Case Report.

Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma and has a poor prognosis. It needs prompt recognition in order to institute timely treatment. Given its relatively low incidence, it is an evolving area of research as well. This case report describes a patient with PCL in the setting of a previously treated myeloma. The report also reviews the clinicopathologic, cytogenetic, and immunophenotypic characteristics of PCL and its management.

Clinical Advancement and Challenges of ex vivo Expansion of Human Cord Blood Cells.

Apart from peripheral blood stem cell (PBSC), umbilical cord blood (UCB) is now a recognized source of stem cells for transplantation. UCB is an especially important source of stem cells for minority populations, which would otherwise be unable to find appropriately matched adult donors. UCB has fewer mature T lymphocytes compared with peripheral blood, thus making a UCB transplantation (UCBT) with a greater degree of HLA mismatch possible. The limited cell dose per UCB sample is however associated with delayed engraftment and a higher risk of graft failure, especially in adult recipients. This lower cell dose can be optimized by performing double unit UCBT, ex vivo UCB expansion prior to transplant and enhancement of the capabilities of the stem cells to home to the bone marrow. UCB contains naïve and immature T cells, thus posing significant challenges with increased risk of infections, graft versus host diseases (GVHD) and relapse following UCBT. Cell engineering techniques have been developed to circumnavigate the immaturity of the T cells, and include virus-specific cytotoxic T cells (VSTs), T cells transduced with disease-specific chimeric antigen receptor (CAR T cells) and regulatory T cell (Tregs) engineering. In this article, we review the advances in UCB ex vivo expansion and engineering to improve engraftment and reduce complications. As further research continues to find ways to overcome the current challenges, outcomes from UCBT will likely improve.

Current Status and Perspectives of Irradiation-Based Conditioning Regimens for Patients with Acute Leukemia Undergoing Hematopoietic Stem Cell Transplantation.

Acute myeloid leukemia and acute lymphoblastic leukemia are the most common indications for allogeneic hematopoietic stem cell transplantation. Total body irradiation (TBI) is an important part of conditioning regimens. TBI-based regimens offer advantages in sanctuary sites but are associated with significant risks of early and late side effects, including pulmonary toxicity, growth retardation, and second malignancy. TBI is also associated with technical problems, such as dose heterogeneity. With evolving techniques in radiation oncology, it is possible to focus the dose to the entire skeleton while sparing the rest of the body. This technique is called total marrow irradiation (TMI). TMI is able to deliver the same or higher doses to bone marrow while reducing toxicity. With the success of TMI, we are moving toward ultra-personalized conditioning. We review the clinical role of the irradiation-based regimens currently in clinical use, emphasizing on their strengths and limitations. Novel technologies with targeted irradiation accompanied by the modern imaging techniques and increased knowledge of the disease process can help us achieve our goal of maximum response with minimum toxicity.

Right orbital edema masquerading a hematologic malignancy.

INTRODUCTION: Multiple myeloma is caused by abnormal proliferation of plasma cells that affects more commonly African Americans. It classically presents with hypercalcemia, renal failure, anemia, and lytic bone lesions. The aim of this article is to present an unusual case of a 63-year-old African-American female with multiple myeloma who presented with worsening right-sided eye swelling for the past 3 weeks and to briefly review ophthalmologic manifestations of multiple myeloma. CASE DESCRIPTION: Our patient's presentation was associated with a throbbing frontal headache, nasal congestion, malaise, and weight loss. Differential diagnosis on admission included giant cell arteritis, conjunctivitis, preseptal cellulitis, glaucoma, acute sinusitis, or cavernous sinus thrombosis. Extensive ophthalmologic evaluation did not show any intraocular abnormality. However, a magnetic resonance imaging of the brain showed hyperintense foci in the right frontal calvarium leading to the eye swelling. Further evaluation revealed pancytopenia, elevated protein levels, and inverse albumin-globulin ratio suggestive of a plasma cell dyscrasia. A skeletal survey revealed multiple osteolytic lesions. Serum and urine protein electrophoresis revealed elevated immunoglobulin G Kappa monoclonal gammopathy. Bone marrow biopsy demonstrated a hypercellular marrow comprised at least 70% mature appearing plasma cells staining positive for CD138. Chemotherapy with cyclophosphamide, bortezomib, and dexamethasone was initiated. After 2 months of chemotherapy, orbital swelling has resolved with decrease in M-spike, immunoglobulin G, and serum kappa light chains. CONCLUSION: This case illustrates an unusual presentation of multiple myeloma which was eye swelling caused by bony infiltration in the calvarium. Although hematologic malignancies tend to have more specific signs and symptoms, they should be included in the differentials of unilateral orbital edema.

Role of Poly Adenosine Diphosphate Ribose Polymerase Inhibitors in Advanced Stage Ovarian Cancer.

Ovarian cancer is one of the leading causes of death from gynecologic cancers. In this present era of cancer treatment, therapeutic options for patients with advanced or recurrent ovarian cancer are limited. The present standard of care treatment for advanced ovarian cancer is a platinum-based doublet chemotherapy (paclitaxel and carboplatin with or without bevacizumab) after a maximum attempt of surgical cytoreduction. However, there are no promising options for the management of patients with ovarian cancer refractory to the platinum-based chemotherapy. Therefore, newer, safe, and more effective treatment modalities are required for patients with advanced or recurrent ovarian cancer. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors have shown an impressive safety profile and anti-tumor efficacy in patients with breast cancer 1 and 2 (BRCA1 and BRCA2) gene-mutated ovarian cancer who were previously treated with the standard of care chemotherapy. We have done a detailed review of the literature to emphasize the role of PARP inhibitors in the treatment of advanced or relapsed ovarian cancer.

Acute Left Internal Carotid Artery and Right Popliteal Artery Occlusion Related to Cisplatin-Gemcitabine Based Chemotherapy.

OBJECTIVES: The increased risk of thromboembolic complications with active cancer is well known. We present this case to highlight that chemotherapy may increase the risk of thromboembolic events even further in cancer patients. METHODS: We report a case of a 64-year-old male with Diffuse Large B-Cell Non-Hodgkin's Lymphoma who presented with left-sided headache and right calf pain two weeks after starting Rituximab/Gemcitabine/Cisplatin/Dexamethasone chemotherapy. Neurological examination was normal, but there was an absent right dorsalis pedis pulse. He subsequently developed left vision loss. CT angiogram of the head and neck revealed occlusion of his left internal carotid artery and poor opacification of the left ophthalmic artery. An angiogram of the right leg further revealed acute occlusion of the popliteal artery. RESULTS: The patient underwent intra-arterial Tissue Plasminogen Activator injection to his lower limb and was started on Low Molecular Weight Heparin. His vision gradually recovered with time. His chemotherapy regimen was changed to RICE (Rituximab, Ifosfamide, Carboplatin, Etoposide). CONCLUSION: Based on literature review, there are numerous similar presentations of arterial thromboembolism in patients on Cisplatin-based chemotherapy. A high index of suspicion for such events should be maintained for patients on chemotherapy presenting with unusual symptoms.

[Transgastric gastro-jejunal anastomosis with flexible endoscope on a biosynthetic model]. / Transgastricus gastrojejunalis anastomosis készítése flexibilis endoszkóppal bioszintetikus modellen.

INTRODUCTION: In the last few years the rapid development of flexible endoscopies has opened new possibilities in minimal invasive procedures. With the help of these techniques the exposure, the risk of complications and the healing period of the patient might be reduced. One of these procedures is the transgastric intervention. Through an incision on the wall of the stomach, the endoscope could be led into the abdominal cavity, where several interventions can be performed. The aim of the study was to examine the technical feasibility and the success of the formation of gastro-jejunal anastomosis. Meanwhile the difficulties of the method could be explored in order to introduce this method in human use. METHOD: A lifelike biosynthetic model was made from a slaughtered domestic pig's gastrointestinal tract (stomach and the first few jejunum loops) which was fixed onto a plastic frame. Two single-channel gastroscopes were inserted into the stomach. On the wall of the stomach an approximately 2 centimetres wide incision was made by the electrocoagulator with a needle-knife. Through it the first jejunum loop was grasped by a foreign-body forceps and then was retracted into the stomach. Subsequently the jejunum loop was held safely with the first endoscope. Parallel to it an incision was made on the jejunum by the electrocoagulator. The authors managed to securely unite the open edges of the gastric wall and the jejunum with endoclips. RESULT: The model was good for practising. The anastomosis is technically feasible and was successfully made on biosynthetic porcine model using the transgastric route. Although the incisions both on the gastric wall and on the jejunum loop were made easily, the fixing of the anastomosis might be questionable. CONCLUSION: It was revealed that more experiments and the development of new, special instruments are needed in order to conduct the anastomosis safely.

[Gastro-entero anastomosis with flexible endoscope with the help of rare-earth magnets on biosynthetic model made of the gastrointestinal tract of slaughtered pigs]. / Flexibilis endoscoppal készített gastroentero anastomosis ritkafödfém mágnesek segítségével sertés gyomorbel traktus felhasználásával készített bioszintetikus modellen.

UNLABELLED: Gastro-entero anastomosis with flexible endoscope with the help of rare-earth magnets on biosynthetic model made of the gastrointestinal tract of slaughtered pigs BACKGROUND: Numerous malignant diseases may cause gastric outlet obstruction. The surgical gastrointestinal bypass, besides the fact that it requires narcosis, is also associated with high risks for patients with poor general condition. Endoscopic insertion of self-expandable metal stent is less invasive, but often causes complications. In the last years some studies examined a new minimal invasive technique, in which magnets are used to create gastroenteric anastomosis. MATERIAL AND METHOD: A biosynthetic model was developed from combined synthetic materials with biogenic specimens taken from slaughtered domestic pigs. The procedure was performed with endoscopic and fluoroscopic guidance. To increase X-ray contrast differences the model was put into physiological saline solution. Two rare-earth magnets (Br: 2500 Gauss, D: 10 mm) with central hole were inserted with the help of a guiding wire and duodenal probe. The first magnet was placed in the first jejunal loop; the second one was placed in the stomach. The gastric magnet was maneuvered using the endoscope. When the magnets reached the right position, the guiding wires were removed to let the magnets stick together. The pressure between the magnets will result in a sterile inflammation on the living tissue which develops adhesion between the bowels, and 7-10 days later anastomosis will develop as a result of the necrosis. RESULT: The biosynthetic model could be used for training endoscopy without sacrificing animals. In the end of the procedure the magnets stuck together across gastric and jejunal walls in all ten cases successfully. By practice the period necessary for the procedure could be decreased from 40 to 20 minutes. CONCLUSION: The technique could be made with standard upper endoscope and instruments, and after practice on living animals it could potentially be a useful solution for complaints of gastric outlet obstruction.

Severe Thrombotic Complication of Eltrombopag in a Cirrhotic Patient.

We present a patient with hepatitis C virus (HCV) and cirrhosis who was treated with eltrombopag for idiopathic thrombocytopenic purpura and was incidentally found to have a right atrial thrombus with extension into the left internal jugular vein. Eltrombopag was discontinued and the patient was treated with thrombectomy and anticoagulation. Given the proposed use of eltrombopag in HCV-associated thrombocytopenia, we advise caution when treating cirrhotics who are at higher intrinsic risk of thrombosis.

Pseudoaneurysm of pulmonary artery: rare complication of systemic chemotherapy.

Pulmonary artery pseudoaneurysm is an uncommon yet fatal clinical entity. Its presentation can mimic a number of common diseases and can be easily missed. As pseudoaneurysm is associated with a number of fatal complications, clinicians should be aware of imaging features which distinguishes pseudoaneurysms from its close differentials. Early recognition and treatment of pseudoaneurysm can prevent fatal outcomes including hemothorax, rupture, or death.

Thrombotic thrombocytopenic purpura and cardiac papillary fibroelastoma: a 'unique coexistence'.

Thrombotic thrombocytopenic purpura (TTP), a complex thrombotic microangiopathy, remains an evolving enigma. A 49-year-old African-American woman presented with acute left hemiplegia, an ischemic cerebrovascular accident involving the right middle cerebral artery. Sequential appearance of thrombocytopenia and evidence of microangiopathic haemolysis led to the diagnosis of acquired idiopathic autoimmune TTP. This was managed with plasma exchange (PEX) and steroids. Early haematologic relapse within a month was managed with the addition of rituximab attaining sustained remission. The patient presented 3 years later with acute confusion and expressive aphasia due to multiple infarcts involving the left parieto-occipital cortex. Transoesophageal echocardiography demonstrated a pedunculated 6 mm mitral valvular mass consistent with a papillary fibroelastoma. Anticoagulation was instituted and the patient was continued on therapeutic oral warfarin. A haematologic relapse of TTP eventually emerged and was managed with PEX, steroids and rituximab. This vignette demonstrates several dilemmas in the clinical presentation, diagnosis and management of TTP in current day practice. Rituximab has adjuvant benefits to PEX and is being investigated as potential first-line therapy. Monitoring ADAMTS13 activity and inhibitor titre, as in our case, prove to have prognostic significance. Cardiac fibroelastomas are rare benign cardiac tumours usually arising from valvular endocardium with thromboembolic potential. One of the proposed mechanisms of origin of these masses is organizing thrombi in the setting of endocardial injury and inflammation questioning a possible link to thrombotic microangiopathy. To the best of our knowledge, this is the first report of this unique coexistence.