Successful Use of Adjunctive Red Blood Cell Exchange Therapy for Treatment of an Acute Hemolytic Reaction After ABO-Incompatible Red Blood Cell Transfusion.

An acute hemolytic transfusion reaction is a potentially fatal complication resulting from the transfusion of mismatched blood products. Symptoms vary from mild to severe depending on how much incompatible antigen was transfused and the nature of the recipient's antibodies. There is no consensus agreement of appropriate management other than discontinuing the transfusion and basic supportive methods including adjunctive pharmacologic agents. A 40-year-old male presented with a gunshot wound to the upper torso. During surgery, the O+ patient lost 1.3 L of blood and postoperatively was inadvertently given one unit of A+ packed red blood cells. The blood bank noticed the error and notified the floor within the hour. An acute hemolytic transfusion reaction had progressed to shock and disseminated intravascular coagulation within hours. The clinical course continued to decline despite a norepinephrine drip and a red blood cell exchange transfusion was implemented within 5 h of the mismatched transfusion. The patient's hematological parameters and clinical markers improved and he was eventually discharged in stable condition. An adjunctive red blood cell exchange transfusion may be useful when treating an ABO-incompatible acute hemolytic transfusion reaction if there has been a large volume mismatched transfusion and a poor clinical response to basic supportive methods.

The absolute percent deviation of IGHV mutation rather than a 98% cut-off predicts survival of chronic lymphocytic leukaemia patients treated with fludarabine, cyclophosphamide and rituximab.

The degree of somatic hypermutation, determined as percent deviation of immunoglobulin heavy chain gene variable region sequence from the germline (IGHV%), is an important prognostic factor in chronic lymphocytic leukaemia (CLL). Currently, a cut-off of 2% deviation or 98% sequence identity to germline in IGHV sequence is routinely used to dichotomize CLL patients into mutated and unmutated groups. Because dissimilar IGHV% cut-offs of 1-5% were identified in different studies, we wondered whether no cut-off should be applied and IGHV% treated as a continuous variable. We analysed the significance of IGHV% in 203 CLL patients enrolled on the original frontline fludarabine, cyclophosphamide and rituximab (FCR) trial with a median of 10 years follow-up. Using the Cox Proportional Hazard model, IGHV% was identified as a continuous variable that is significantly associated with progression-free (PFS) and overall survival (OS) (P < 0·001). Furthermore, we validated this finding in 323 patients treated with FCR off-protocol and in the total cohort (n = 535). Multivariate analysis revealed a continuous trend. Higher IGHV% levels were incrementally associated with favorable PFS and OS in both FCR-treated cohorts (P < 0·001, both cohorts). Taken together, our data suggest that IGHV% is a continuous variable in CLL patients treated with FCR.

Mast cell leukemia (MCL): Clinico-pathologic and molecular features and survival outcome.

Mast cell leukemia (MCL) is a very rare subtype of systemic mastocytosis (SM). We have identified 13 such patients (5.9%) among 218 patients with SM seen at our institution between 1994 and 2016. Patients with MCL had poor survival (median 31.6 months); response to various therapies was rare and not durable. Clinical course may be affected by concurrent associated hematologic neoplasm and different genetic profiles. More research is required to decipher this rare and enigmatic SM subtype.

FDG PET/CT in Malignant Eccrine Spiradenoma.

Malignant eccrine spiradenoma is very rare skin appendageal cancer. We report a 64-year-old man who presented with a 6-month history of a rapidly growing mass in his groin. Physical examination revealed a 10-cm, ulcerated, fungating mass involving the entire right ilioinguinal region. PET/CT scan demonstrated intense FDG-avid lesion in the inguinal region. Histopathology of the lesion was compatible with malignant eccrine spiradenoma. He required extensive tumor resection followed by chemotherapy and radiotherapy.

Chronic Epstein Barr virus infection leading to classical Hodgkin lymphoma.

BACKGROUND: Chronic Epstein Barr virus (EBV) infection in an immunocompetent host has been described however it is not a common entity. It has been linked to many lymphoproliferative disorders and achieves such via many molecular mechanisms, some of which are poorly understood. In addition to infectious mononucleosis, the EBV is linked to various other hematological pathologies and autoimmune disorders. CASE PRESENTATION: We describe the case of an elderly immunocompetent female who presented with non-specific symptomatology, lymphadenopathy, cytopenias, elevated autoantibody titers and a crescent EBV viral load that were suggestive of a multisystemic inflammatory disease related to EBV. Extensive work up including multiple bone marrow biopsy and lymphoid tissue procedures ultimately led to the diagnosis of Hodgkin lymphoma. CONCLUSION: EBV-related lymphomagenesis is complex and through the utilization of its nuclear antigens and latent membrane proteins the virus is able to shape the microenvironment to promote the various pathologies seen. Moreover, the diagnosis of EBV-associated lymphoproliferative disorders might be challenging when they present in immunocompetent individuals. Our case also represents an emphatic reminder for clinicians that spontaneous regression of lymphadenopathy is not exclusive of low-grade lymphoid malignancies.

Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine.

BACKGROUND: Despite advances in molecular medicine over recent decades, there has been little advancement in the treatment of osteosarcoma. We performed comprehensive molecular profiling in two cases of metastatic and chemotherapy-refractory osteosarcoma to guide molecularly targeted therapy. PATIENTS AND METHODS: Hybridization capture of >300 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from tumor samples from two patients with recurrent, metastatic osteosarcoma. The DNA from each sample was sequenced to high, uniform coverage. Immunohistochemical probes and morphoproteomics analysis were performed, in addition to fluorescence in situ hybridization. All analyses were performed in CLIA-certified laboratories. Molecularly targeted therapy based on the resulting profiles was offered to the patients. Biomedical analytics were performed using QIAGEN's Ingenuity® Pathway Analysis. RESULTS: In Patient #1, comprehensive next-generation exome sequencing showed MET amplification, PIK3CA mutation, CCNE1 amplification, and PTPRD mutation. Immunohistochemistry-based morphoproteomic analysis revealed c-Met expression [(p)-c-Met (Tyr1234/1235)] and activation of mTOR/AKT pathway [IGF-1R (Tyr1165/1166), p-mTOR [Ser2448], p-Akt (Ser473)] and expression of SPARC and COX2. Targeted therapy was administered to match the P1K3CA, c-MET, and SPARC and COX2 aberrations with sirolimus+ crizotinib and abraxane+ celecoxib. In Patient #2, aberrations included NF2 loss in exons 2-16, PDGFRα amplification, and TP53 mutation. This patient was enrolled on a clinical trial combining targeted agents temsirolimus, sorafenib and bevacizumab, to match NF2, PDGFRα and TP53 aberrations. Both the patients did not benefit from matched therapy. CONCLUSIONS: Relapsed osteosarcoma is characterized by complex signaling and drug resistance pathways. Comprehensive molecular profiling holds great promise for tailoring personalized therapies for cancer. Methods for such profiling are evolving and need to be refined to better assist clinicians in making treatment decisions based on the large amount of data that results from this type of testing. Further research in this area is warranted.