Acquired Factor VII Deficiency Associated With Chronic Myeloid Leukemia Blast Crisis.

Factor VII (FVII) is an important, vitamin K-dependent clotting factor. Acquired FVII deficiency is a rare entity that is associated with serious bleeding complications. We report a case of acquired FVII deficiency in a patient with recurrent chronic myeloid leukemia in blast crisis who developed bilateral retinal hemorrhages. The coagulopathy was corrected with the initiation of chemotherapy and subsequent reduction in peripheral blast count.

Special case of a patient in the blast phase of chronic myeloid leukemia successfully treated with tocilizumab during critical SARS-CoV-2 infection.

The medical care of patients with hematological malignancies who develop coronavirus disease 2019 (COVID-19) has been a major challenge during the current pandemic. We herein describe a patient in the blast phase of chronic myeloid leukemia who was hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient was successfully treated with tocilizumab, and intubation was avoided. The severity of SARS-CoV-2 infection is mostly related to a severe acute respiratory distress syndrome that develops secondary to cytokine release syndrome, and interleukin 6 is the main cytokine involved in cytokine release syndrome. Very few reports have described the use of tocilizumab in patients with hematologic malignancies who develop SARS-CoV-2 infection, although a few cases of patients with multiple myeloma have been reported. To our knowledge, however, this is the first report of a SARS-CoV-2-infected patient in the blast phase of chronic myeloid leukemia who had a favorable response to treatment with tocilizumab. The management of patients with hematological malignancies who become infected with SARS-CoV-2 is a major challenge for practitioners, necessitating more specific research in this direction.

Hemorrhage in acute promyelocytic leukemia: Can it be predicted and prevented?

Hemorrhagic death is the leading cause of treatment failure in acute promyelocytic leukemia (APL). Our ability to identify patients at greatest risk of hemorrhage, and to actively prevent hemorrhage, remains limited. Nevertheless, some data is available to guide contemporary clinical practice and future investigation. Circulating disease burden, best represented by the peripheral WBC / blast count, is the most consistent predictor of major and fatal bleeding risk. In contrast, laboratory markers of disseminated intravascular coagulation (DIC) appear to be poor predictors. A number of interventions have been posited to reduce bleeding risk. Prompt initiation of all-trans retinoic acid (ATRA), avoidance of invasive procedures, transfusion support, and cytoreduction all have theoretical merit. Though they lack strong evidence to support their benefit with respect to bleeding, they are associated with limited risks, and are therefore advisable. Low-dose therapeutic heparin and antifibrinolytics have not shown the ability to positively modify bleeding risk, and heparin has been associated with harm. Thrombomodulin has shown promise in limited retrospective studies however further prospective data are needed. rFVIIa may have a role in cases of life-threatening bleeding however evidence is largely anecdotal. Additional studies evaluating the above interventions, and investigating other potential interventions are needed.

Severe COVID-19 infection in a patient with a blastic transformation of a chronic myeloid leukemia and severe treatment-induced immunosuppression: a case report.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the globe, leading to the declaration of a pandemic. While most present mild symptoms, it appears as though nearly 20% of confirmed patients develop significant complications. At this time of uncertainty, we are struggling to provide appropriate care to hematological cancer patients. We need to weigh the risks and benefits of giving cancer treatment against the odds of infecting them with COVID-19. As hematological cancer patients are immunocompromised and there are high chances of exposure during hospital visits, they can get infected and outcome can be fatal. So in this case report, we intend to discuss the possible impact of the current COVID-19 pandemic on patients with acute leukaemia in terms of diagnosis, chemotherapy, and prophylactic measures.

Chronic myeloid leukemia extramedullary blast crisis presenting as central nervous system leukemia: A case report.

RATIONALE: Childhood chronic myeloid leukemia (CCML) is a malignant disease of granulocyte abnormal hyperplasia that is caused by clonal proliferation of pluripotent stem cells. The condition is relatively rare, accounting for 2.0% to 3.0% of cases of childhood leukemia. In addition, the incidence of extramedullary blast crisis in CCML presenting as central nervous system (CNS) blast crisis remaining chronic phase of the disease in bone marrow is extremely unusual. PATIENT CONCERNS: We report a case of childhood chronic myelogenous leukemia that abandoned treatment, resulting in chronic myelogenous leukemia transforming into extramedullary blast crisis resulting in CNS leukemia, accompanied by the chronic phase of the disease in bone marrow. DIAGNOSES: Chronic myeloid leukemia extramedullary blast crisis presenting as CNS leukemia without blast crisis in bone marrow. INTERVENTIONS: Following high-dose systemic and intrathecal chemotherapy, the patient continued to do well. LESSONS: High-dose systemic and intrathecal chemotherapy is safe and helpful for CCML extramedullary blast crisis. A long-term follow-up is crucial.

[Initial presentation of lymphoblastic crisis in a pediatric chronic myelogenous leukemia patient].

A 9-year-old girl was referred to our hospital because of facial palsy. Both physical and blood examination revealed hepatosplenomegaly and leukocytosis, respectively. A bone marrow examination demonstrated marked hypercellularity involving myeloblasts and lymphoblasts. Based on these results, we suspected mixed phenotype acute leukemia. However, her leukemic blasts expressed B-cell antigens, and a chromosomal analysis of her bone marrow cells revealed the following karyotype: 46, XX, t (9;22) (q34;q11.2). All her neutrophils were positive for the breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion protein. Based on these findings, she was diagnosed with a lymphoblastic crisis of chronic myelogenous leukemia (CML). Combined chemotherapy, involving imatinib, resulted in complete molecular remission. She received cord blood transplant (CBT) during the first complete remission; she is alive and has not suffered a relapse since two years after the CBT. The sudden onset of a blastic crisis in pediatric CML is rare, and it may be difficult to distinguish such cases from de novo Ph-positive leukemia. For diagnostic purposes, it is essential to consider a patient's clinical course and blood test results.

Brain infarction and blasts with bilobed nuclei in a patient with monocytic acute myeloid leukemia mimicking acute promyelocytic leukemia.

We are presenting a case of an adult male patient with monocytic acute myeloid leukemia (AML) who had on presentation brain infarction and bilobed nuclei had been demonstrated in many of the leukemic blasts. There was no laboratory evidence of acute disseminated intravascular coagulopathy, on presentation or later on. Initially the diagnosis of acute promyelocytic leukemia (APL) was considered, so all trans-retinoic acid (ATRA) was added to induction chemo therapy. As the diagnosis of APL was ruled out, based on the flow cytometry, fluorescent in situ hybridization and polymerase chain reaction findings, the ATRA was discontinued and the patient continued on the standard AML chemo therapy induction regimen. Later on chromosomal analysis was also normal. Sever dehydration on presentation, would have contributed to brain infarction. AML particularly monocytic, can mimic APL, especially its microgranular variant. The possible ATRA therapy side effects, can be avoided by early confirmation of the diagnosis.

The percentage of peripheral blood blasts on day 7 of induction chemotherapy predicts response to therapy and survival in patients with acute myeloid leukemia.

BACKGROUND: Rapid clearance of peripheral blood blasts (PBBs) predicts complete remission (CR) and survival in patients with acute myeloid leukemia (AML). We aimed to explore the correlation between induction therapy response, outcome, and the PBB percentage. METHODS: Forty-six consecutive patients with de novo AML (excluding acute promyelocytic leukemia) were enrolled in this study. Flow cytometry was performed to identify cells with a leukemia-associated aberrant immunophenotype in the initial bone marrow aspirate and in peripheral blood on day 7 of induction therapy. RESULTS: The PBB percentage on day 7 (D7PBBP) was significantly lower in patients who achieved CR (0.03% (0.0%, 0.45%)) than in those who did not (10.85% (1.13%, 19.38%); u = -3.92, P < 0.001). The CR rate was significantly higher among patients with a D7PBBP of <0.945% (84.62%, 22/26) than among those with a D7PBBP of = 0.945% (25.0%, 5/20; χ2 = 16.571, P < 0.001). D7PBBP was significantly correlated with overall survival (OS; r = -0.437, P = 0.003) and relapsefree survival (RFS; r = -0.388, P = 0.007). OS and RFS were significantly higher in patients with a D7PBBP of <0.43% than in those with a D7PBBP of ≥ 0.43% (P < 0.001 and P = 0.039, respectively). D7PBBP was also found to be an independent prognostic indicator in multivariate analysis for both OS (P = 0.036) and RFS (P = 0.035). CONCLUSION: D7PBBP may be an important risk factor for the achievement of complete remission, for overall survival, and for relapse-free survival.

Renal cortical necrosis secondary to thrombotic microangiopathy in the context of acute promyelocytic leukaemia blast crisis.

A 37-year-old patient was transferred to Haematology from the ENT Emergency Department where he had been admitted due to tonsillitis. He displayed anaemia and leukopenia and had agranulocytosis in the study. A day later the patient had blast crisis, and was diagnosed with myeloid acute leukaemia. Due to blast crisis the patient experienced sudden back pain, with oliguria and renal function deterioration followed by anaemia, in the context of haemolysis consistent with thrombotic microangiopathy, and as such, we were consulted. We began treatment with plasmapheresis and on the following day we performed haemodialysis (we carried out a total of 12 sessions of plasmapheresis until haemolysis disappeared). Five days later there was respiratory failure, and the patient was consequently transferred to the Intensive Care Unit, where he continued treatment with plasmapheresis and haemodialysis. The patient remained anuric thereafter, requiring haemodialysis, with no sign of renal recovery. Once platelet levels normalised with haematology chemotherapy, a percutaneous renal biopsy was performed, which confirmed the diagnosis of cortical necrosis. Finally, the patient underwent renal replacement therapy by regular haemodialysis.

Leukemic blasts with the paroxysmal nocturnal hemoglobinuria phenotype in children with acute lymphoblastic leukemia.

It has been proposed that genomic instability is essential to account for the multiplicity of mutations often seen in malignancies. Using the X-linked PIG-A gene as a sentinel gene for spontaneous inactivating somatic mutations, we previously showed that healthy individuals harbor granulocytes with the PIG-A mutant (paroxysmal nocturnal hemoglobinuria) phenotype at a median frequency (f) of ∼12 × 10(-6). Herein, we used a similar approach to determine f in blast cells derived from 19 individuals with acute lymphoblastic leukemia (ALL) and in immortalized Epstein-Barr virus-transformed B-cell cultures (human B-lymphoblastoid cell lines) from 19 healthy donors. The B-lymphoblastoid cell lines exhibited a unimodal distribution, with a median f value of 11 × 10(-6). In contrast, analysis of the f values for the ALL samples revealed at least two distinct populations: one population, representing approximately half of the samples (n = 10), had a median f value of 13 × 10(-6), and the remaining samples (n = 9) had a median f value of 566 × 10(-6). We conclude that in ALL, there are two distinct phenotypes with respect to hypermutability, which we hypothesize will correlate with the number of pathogenic mutations required to produce the leukemia.