Hematologic complications in a patient with Glycine soja polyagglutination following fresh frozen plasma transfusion.

CONCLUSIONS: Polyagglutination is a rare and underdiagnosed condition, characterized by agglutination of red blood cells(RBCs) with almost all ABO-compatible adult sera. Polyagglutination can occur when a cryptantigen is exposed on RBCs via microbial enzyme activity. Becausenearly all adults naturally produce antibodies against cryptantigens, transfusion of plasma can cause unexpected hemolysis and hematologic complications, such as thrombocytopenia and disseminated intravascular coagulation, in patients whose cryptantigens are exposed. We report a case of Glycine soja polyagglutination occurring in a 60-year-old African-American man with disseminated methicillin-resistant Staphylococcus aureus (MRSA) infection. Prior to transfusion, the patient developed severe anemia of unknown etiology. Following transfusion of 3 units of fresh frozen plasma (FFP), his RBC count could not be determined for 24 days because of RBC agglutination in his blood sample. In addition, the FFP transfusion correlated with the rapid development of severe, transfusionrefractory thrombocytopenia and anemia. The perplexed clinical team consulted the blood bank. A direct antiglobulin test demonstrated 1+ mixed-field reactivity with both monoclonal anti-IgG and anti-C3d. Lectin panel testing showed reactivity with only Glycine soja, confirming the condition. Subsequently, plasma components were avoided, and RBC and platelet (PLT) components were washed prior to transfusion. After a 44-day hospitalization involving the transfusion of 22 units of RBCs and 13 units of PLTs, the patient was discharged to a long-term care facility. The patient's confounding hematologic complications can best be explained by polyagglutination, which developed secondary to the severe MRSA infection. The FFP transfusion likely passively transferred antibodies that bound to the patient's RBC cryptantigens, leading to RBC agglutination and anemia. The development of severe thrombocytopenia may be related to cryptantigen exposure on the patient's PLTs. Although difficult to identify, polyagglutination needs to be recognized to appropriately manage hemotherapy. The purpose of this case study is to report hematologic complications following FFP transfusion in a patient with Glycine soja polyagglutination, a rarely described condition.

Acute leukemia with PICALM-MLLT10 fusion gene: diagnostic and treatment struggle.

Patients with various hematologic malignancies, including acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), diffuse histiocytic lymphoma, and granulocytic sarcoma, have sometimes been shown to carry the PICALM-MLLT10 fusion gene (alias CALM-AF10) by various cytogenetic methodologies. Cases with the PICALM-MLLT10 fusion gene can involve a diagnostic dilemma for the following reasons: (1) the fusion gene occurs very rarely, (2) the cases do not have a distinct myeloid or lymphoid morphology and cells often appear immature, (3) cases usually have a mixed T-cell and myeloid phenotype, and (4) cases often have a mixed clinical presentation (e.g., mediastinal mass in a patient with AML). A 27-year-old woman was diagnosed with AML with the PICALM-MLLT10 fusion gene. The patient was treated on an AML regimen and achieved a complete remission. Although the reported treatment of these patients varies greatly, outcome remains very poor in the vast majority. Furthermore, central nervous system involvement at diagnosis and relapse are reported in pediatric populations. Routine acute leukemia fluorescence in situ hybridization panels do not include a probe for the PICALM-MLLT10 fusion gene, and therefore diagnosis can be made only when karyotyping is available; that delay can result in initial misdiagnosis and mistreatment. The case report and literature review here (including discussion of the poor prognosis and of management, including CNS prophylaxis) are intended to raise awareness and to inform about PICALM-MLLT10 in acute leukemia.

Isolated trisomy 10 in an infant with acute myeloid leukemia: a case report and review of literature.

Trisomy 10 as the sole cytogenetic abnormality in AML is rare, with an incidence rate of < 0.5%. It tends to affect the elderly and is extremely rare in pediatric patients. We describe a case of an 8-month-old Caucasian baby who presented with prominence of left eye and fever without lymphadenopathy or hepatosplenomegaly. Bone survey showed diffuse periosteal reaction in the femur, pelvis, maxillary and orbital bones (with fracture). CBC revealed normal white blood cell count with increased blasts, mild anemia and moderate thrombocytopenia. Bone marrow biopsy showed increased myeloblasts with bilineage dysplasia and 3-4+ reticulin fibrosis. Flow cytometry revealed blasts positive for CD34, CD33, and MPO and negative for CD7, CD13, and HLA-DR. Trisomy 10 was demonstrated by chromosome analysis and fluorescence in-situ hybridization. The patient received induction chemotherapy and achieved complete clinical and hematologic remission at day 28. However, he relapsed after three cycles of chemotherapy. Compared to the two other reported pediatric cases, our patient has some unique features such as much younger age and additional findings such as bilineage dysplasia and bone marrow fibrosis. Both reported cases and our case were classified as AML-M2 indicating that this may be a common subtype in pediatric patients. Bone involvement was present in our patient and one other case and both had similar immunophenotype (CD33+, CD7-). These findings suggest that isolated trisomy 10 may be associated with distinct clinicopathologic features in pediatric AML. Studies on additional patients are needed to establish this association.

Hyperostosis - an unusual radiographic presentation of Myelodysplastic Syndrome transformed to Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is also referred to non-lymphocytic leukemia in the literature. It comprises about 15% of the childhood leukemia. There are multiple subtypes of AML from M0-M7 with approximately 45% of the cases being M0-M2 and the remaining subtypes being rare. The definitive diagnosis relies on bone marrow biopsy showing bone marrow infiltration with leukemic cells. We describe a rare radiographic presentation of myelodysplastic syndrome (MDS) transformed to AML in an 8 month old boy who presented with a orbital wall fracture, periosteal reaction, and mixed lytic and sclerotic lesions.

Amyloidosis, Evans syndrome and management options of lymphoplasmacytic lymphoma.

A 77-year-old man presented with Evans syndrome (ES), hard palate thickening, gastrointestinal (GI) hemorrhage, acute myocardial infarction (AMI) and pleural and pericardial effusions. The patient responded well to emergent ES treatment with high-dose steroids and intravenous immunoglobulin. Investigation revealed lymphoplasmacytic lymphoma (LPL) as well as amyloidosis in the hard palate, lymph nodes, and pericardium. Considering his age, non-myelosuppressive agents were administered, with the exception of dose-reduced cyclophosphamide. The patient developed neutropenic fever, atrial fibrillation and subsequently died. This report describes the first LPL patient with ES. LPL is generally an indolent disease. However, as in our patient, it can be life threatening because of its complications. ES contributed to his GI hemorrhage, severe anemia, and thus AMI at the time of presentation. Probable cardiac amyloidosis played a role in the latter phase (i.e. cardiac arrhythmia and hypotension during sepsis). Although rare, the presence of ES and amyloidosis should be investigated diligently in elderly LPL patients. Instead of aggressive myelosuppressive chemotherapy agents, targeted therapies might be considered in these fragile patients.

Chemotherapy and dasatinib induce long-term hematologic and molecular remission in systemic mastocytosis with acute myeloid leukemia with KIT D816V.

Dasatinib has been reported to potently inhibit juxtamembrane domain mutant KIT(D816V) autophosphorylation and KIT-dependent activation of down stream signaling important for cell growth and survival of neoplastic cells. Additionally, dasatinib induced apoptosis in mast cell and leukemia cell lines expressing KIT(D816V). Here, we present the first case report of long-term hematologic and molecular remission achieved with combined treatment with chemotherapy and dasatinib in a patient with systemic mastocytosis (SM) and acute myeloid leukemia (AML) with mutant KIT(D816V) expression. A 50-year-old male presented with pancytopenia, organomegaly, lymphadenopathy, and lytic bone lesions in the pelvis. The patient was found to have systemic mastocytosis (SM) and acute myelogeneous leukemia (AML) positive for KIT(D816V) and therefore diagnosed with SM with an associated clonal hematological non-mast cell lineage disease (SM-AHNMD). Both primary CD34+ cells containing myeloblasts and CD34- cells containing mastocytes obtained from the diagnostic BM lost viability markedly by in vitro dasatinib treatment. In addition, dasatinib diminished activity of STAT5, STAT3, AKT and ERK and attenuated the levels of c-KIT. The patient achieved a hematologic complete remission (HCR) by two induction chemotherapies with residual mastocytes. Dasatinib (70mg PO bid, days 1-4) was added to consolidation treatments composed of four cycles of high dose cytarabine and was then continued as maintenance therapy (50mg PO bid). Periodic bone marrow (BM) aspirate/biopsies (eight over 18 months) were performed. The patient remained in HCR, and the mastocyte burden decreased by 50%. The bone lytic lesions improved. The KIT(D816V)mutation progressively decreased and became undetectable in the last three BM analyses. This result was confirmed by an independent laboratory showing a lack of c-KIT mutation in both CD34+ cells and CD34- cells in the last BM. No significant adverse effects of dasatinib occurred. Dasatinib has in vitro and in vivo efficacy in SM-AML patients with KIT(D816V) mutation. Along with chemotherapy, dasatinib should be considered in these patients particularly if they cannot undergo allogeneic stem cell transplantation for this poor prognostic AML.