Study for the Diagnostic Screening of Paroxysmal Nocturnal Hemoglobinuria in Older Patients with Unexplained Anemia and/or Cytopenia.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that may lead to weakness and death of patients, if unrecognized and untreated. Although consensus guidelines were reviewed recently for the diagnostic screening of PNH with multi-parameter flow cytometry (FCM), until now, no study has investigated the efficiency of such clinical indications in older patients. METHODS: Overall, 20 centers participated in the study and a total of 1,689 patients were included, 313 of whom were at geriatric age and 1,376 were aged 18 - 64 years. We evaluated the efficiency of consensus clinical indications for PNH testing using FCM in peripheral blood samples and compared the results of older patients and patients aged 18 - 64 years. RESULTS: PNH clones were detected positive in 7/313 (2.2%) of the older patients. Five (74.4%) of the patients with PNH clones had aplastic anemia, 1 had unexplained cytopenia, and 1 patient had myelodysplastic syndrome (MDS) with refractory anemia. PNH clones were not detected in any older patients who were screened for unexplained thrombosis, Coombs (-) hemolytic anemia, hemoglobinuria, and others (e.g., elevated lactate dehydrogenase (LDH), splenomegaly). We detected PNH clones in 55/1376 (4%) samples of the patients aged under 65 years. Forty-two (76.4%) patients with PNH clones had aplastic anemia, 2 patients had Coombs (-) hemolytic anemia, 3 patients had unexplained cytopenia, 1 patient had MDS with refractory anemia, 1 patient had hemoglobinuria, and 6 (10.9%) had others (e.g., elevated LDH, splenomegaly). PNH clones were not detected in any patients who were screened for unexplained thrombosis. There was no statistical difference between the geriatric population and patients aged 18 - 64 years in terms of clinical indications for PNH screening with FCM (p = 0.49). CONCLUSIONS: Our results showed that the current clinical indications for PNH screening with FCM were also efficient in older patients. We suggest that older patients with unexplained anemia, myelodysplastic syndrome with refractory anemia, and unexplained cytopenia should be screened for PNH with FCM to identify patients who would benefit from treatment.

Mast cell leukemia associated with undefined morphology and chronic basophilic leukemia.

BACKGROUND: Mast cell leukemia (MCL) is rare type of neoplasia with an incidence of 1% in a large series of 342 adult patients with systemic mastocytosis (SM). Chronic basophilic leukemia (CBL) is an extremely rare type of leukemia with appearance of 7 cases in the literature. CASE PRESENTATION: A 73 year-old female patient who presented with weaknes, had a prolonged duration of hematologic remission after treatment of her CBL by hydroxyurea (HU). Evolution of SM occurring as a second neoplasia concurrently with relapse of de novo CBL was demonstrated by mast cells (MCs) infiltration in the bone marrow (BM) biopsy and smear and increase in tryptase level. Transformation to MCL with simultaneous occurrance of accelerated phase of CBL were documented by the appearance of MCs in both BM and peripheral blood (PB) smears, antigen expressions detected by flow cytometry and spesific stains. Sequence analysis of c-kit gene revealed c-kit exon 11 K550N mutation. Undefined associations of MCL with different mast cell morphology, increase in IL-6 level and accelerated phase of de novo CBL was described. CONCLUSION: Elevations in CRP and IL-6 levels occurring with increases in basophil counts to high levels revealed that febrile episodes with abdominal pain seen in our patient were induced by increase in IL-6 levels released from neoplastic basophils. Neoplastic basophils with diffuse and coarse basophilic granules possibly mimic neutrophils with toxic granules and cause wrong characterization of neoplastic basophils as neutrophils by the automated blood cell counters and misleaded physicians.

Is the BFM Regimen Feasible for the Treatment of Adult Acute Lymphoblastic Leukemia? A Retrospective Analysis of the Outcomes of BFM and Hyper-CVAD Chemotherapy in Two Centers.

Multiple induction regimens have been developed for adult patients with acute lymphoblastic leukemia (ALL). However, there have been no prospective randomized trials that directly compare these regimens. In this study, we wanted to evaluate the outcome of 50 adult ALL patients treated with BFM (i.e. Berlin-Frankfurt-Munster, n = 20) and hyper-CVAD (n = 30) protocols between March 2006 and October 2012. The median age was 25 years in the BFM group and 30.5 years in the hyper-CVAD group with a male/female ratio of 15:5 and 17:13, respectively. Forty-five percent of the patients in the BFM group and 30.3% in the hyper-CVAD group were <25 years old. The majority of cases were B cell in origin (80% in the BFM group and 70% in the hyper-CVAD group). Complete remission after induction therapy was achieved in 95 and 96% of the patients, respectively. The median follow-up time was 37 months. The 5-year survival rate was higher in the BFM group than in the hyper-CVAD group (59 vs. 34%). There were also no complications which could cause a delay during the hyper-CVAD regimen. Both chemotherapies were well tolerated. None of the patients died from drug-related toxicity. Only mild liver enzyme elevations were seen as toxicity in the BFM group; these did not cause any delay in therapy. The BFM regimen seems to be feasible for adult patients with ALL in terms of tolerability and efficacy, especially in young adults.

Ischemic stroke after recombinant factor VIIa treatment in acquired hemophilia A patient.

Acquired hemophilia is a rare, life-threatening coagulopathy in adults caused by the development of autoantibodies against factor VIII. Bypass agents such as recombinant factor VIIa (rFVIIa) are usually preferred for bleeding control; however, thromboembolic complications may occur. We report here a case that presented with extensive cutaneous and mucosal bleedings due to factor VIII inhibitors and was treated successfully with rFVIIa and steroid therapy, but was complicated with a life-threatening thromboembolic attack during follow-up.