An Unusual Presentation of Extramedullary Relapse Following Blinatumomab in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.

In adult patients, extramedullary relapse (EMR) in B-acute lymphoblastic leukemia (B-ALL) has a pejorative prognosis, especially after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Blinatumomab, a bispecific CD3/CD19 antibody, is approved for relapsed/refractory acute lymphoblastic leukemia (ALL) and has proven its efficacy with good complete response (CR) rates and molecular responses in several trials. Unusual sites of relapse following treatment with blinatumomab for ALL are rarely reported. We describe the case of a 23-year-old male with B-ALL characterized as Philadelphia chromosome-positive without extramedullary lesions at diagnosis. He benefited from a matched-related donor allo-HSCT at first remission. A relapse in the bone marrow and central nervous system was diagnosed four months later. A treatment with blinatumomab was initiated with the obtention of CR after one cycle. During the third cycle of blinatumomab, multiple sites of EMR occurred initially with a painless swelling appearing in the areolas and the nipples, followed by bilateral testicular hypertrophy and moderate paraplegia. A diagnosis of leukemic infiltration on the areola-nipple complex was made by cytological analysis of the fine-needle aspiration of the left areola. The analysis of bone marrow was normal, but molecular BCR-ABL was positive. Systemic chemotherapy with hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and cycles of blinatumomab with nilotinib was initiated in association with intrathecal chemotherapy and whole-brain radiation therapy. Clinical, molecular, and central nervous remissions were obtained. We report this case to describe multiple sites of EMR of B-ALL with atypical breast infiltration in an adult male patient following treatment with blinatumomab.

Cold agglutinins revealed by abnormalities to the cell blood count: a case report.

Cold agglutinin are erythrocyte antibodies which possess the property of agglutinating red blood cells at temperatures of below 37°C, this phenomenon is reversible after heating. This is usually immunoglobulin M (IgM) class. Their pathogenicity is much more related to their temperature range of activity than their title. As we report in this observation, cold hemagglutination makes it difficult to interpret certain immunological tests such as ABO Rh blood grouping or searching for irregular antibodies (SAI). The discovery of cold agglutinins can be fortuitous revealing itself by disturbances and aberrations in the results of blood count or as part of a suggestive clinical or laboratory table cold hemagglutinin disease. The search for a lymphoid hematological at their diagnosis should be systematic.

Rare and unusual case of anti-factor XI antibodies in patient with plasma cell leukemia.

BACKGROUND: The acquired inhibitors of coagulation have been observed in very rare cases of monoclonal gammopathies. We report a very rare case of anti-factor XI antibodies in patient with plasma cell leukemia (PCL). CASE PRESENTATION: This is a 59-year-old male patient without pathological history, admitted to the nephrology department for management of renal insufficiency and anemia syndrome. The history and physical examination revealed stigmata of hemorrhagic syndrome including hemothorax and hemoptysis. The hemostasis assessment showed an isolated prolonged activated partial thromboplastin time (APTT) with APTT ratio = 2.0.The index of circulating anticoagulant (37.2%) revealed the presence of circulating anticoagulants. The normalized dilute Russell viper venom time ratio of 0.99 has highlighted the absence of lupus anticoagulants. The coagulation factors assay objectified the decrease of the factor XI activity corrected by the addition of the control plasma confirming the presence of anti-factor XI autoantibodies. In addition, the blood count showed bicytopenia with non-regenerative normocytic normochromic anemia and thrombocytopenia. The blood smear demonstrated a plasma cell count of 49% (2842/mm3) evoking PCL. The bone marrow was invaded up to 90% by dystrophic plasma cells. The biochemical assessment suggested downstream renal and electrolyte disturbances from exuberant light chain production with abnormalities including hyperuricemia, hypercalcemia, elevated lactate dehydrogenase, non nephrotic-range proteinuria and high level of C reactive protein. The serum protein electrophoresis showed the presence of a monoclonal peak. The serum immunofixation test detects the presence of monoclonal free lambda light chains. He was treated with velcade, thalidomide and dexamethasone. The patient died after 2 weeks despite treatment. CONCLUSION: Both PCL and anti-factor XI inhibitors are two very rare entities. To the best of our knowledge, this is the first reported case of a factor XI inhibitor arising in the setting of PCL. Factor inhibitors should be suspected in patients whose monoclonal gammopathies are accompanied by bleeding manifestations.

Severe hemolytic disease of the premature newborn due to RH1 incompatibility: a case report.

We report a case of dramatic outcome of severe hemolytic disease in a newborn due to RH1 incompatibility. A newborn with A RH1 blood group was admitted in the Mohammed V Military Teaching Hospital for the problem of hydrops fetalis associated with RH1 incompatibility. The blood group of his mother, aged 31, was AB RH1-negative and that of his 37 year old father was A RH1. The mother had a history of 4 term deliveries, 3 abortions, and 1 living child. There was no prevention by anti-D immunoglobulin postpartum. The mother's irregular agglutinin test was positive and the pregnancy was poorly monitored. The laboratory tests of the newborn showed a high total serum bilirubin level (30 mg/L) and macrocytic regenerative anemia (Hemoglobin=4 g/dL, mean corpuscular volume = 183 fL, reticulocytes count =176600/m3). The blood smear showed 1256 erythroblasts per 100 leukocytes, Howell-Jolly bodies and many macrocytes. The direct antiglobulin test was positive. He was transfused with red blood cell concentrates and treated with conventional phototherapy. The evolution was unfavourable; he died three days after the death of his mother. The monitoring of these high-risk pregnancies requires specialized centers and a close collaboration between the gynaecologist and the blood transfusion specialist to strengthen the prevention, as well as clinico-biological monitoring in patients with a history of RH1 fetomaternal alloimunization.