Foetal liver infusion in a chronic myeloid leukemia patient with busulphan toxicity

A 36-year-old man suffering from chronic myeloid leukemia (in chronic phase) was initially treated with busulphan. At the end of 6 months of follow-up he developed bone marrow aplasia. He was given single foetal liver infusion therapy. The patient recovered fully from aplasia. He continued in chronic phase for more than 7 years with intermittent busulphan therapy.     

Regression of syndesmophyte after bone marrow transplantation for acute myeloid leukemia in a patient with ankylosing spondylitis: a case report

ABSTRACT: INTRODUCTION: Disease progression of ankylosing spondylitis has been considered irreversible. However, wereport a case of spontaneous regression of syndesmophyte development following allogeneicperipheral blood stem cell transplantation in a patient with acute myeloid leukemia, who wasalso diagnosed as having ankylosing spondylitis. To the best of our knowledge, this is thefirst case report presenting the partial radiologic regression of syndesmophytes. CASE PRESENTATION: A 39-year-old man with active ankylosing spondylitis achieved clinical remission and partialradiological regression of cervical spine syndesmophytes following a peripheral blood stemcell transplantation for acute myeloid leukemia. Our patient received an allogeneic peripheralblood stem cell transplantation following a pre-transplantation conditioning regimen of totalbody irradiation and cyclophosphamide. The donor was a human leukocyte antigen-matched29-year-old man. Our patient has remained asymptomatic and has received no medication forankylosing spondylitis for nearly three years. CONCLUSIONS: Several explanations are proposed for the regression of syndesmophytes and clinicalimprovement in active ankylosing spondylitis observed in our patient, including changes inbone remodeling and immune reconstitution following stem cell transplantation, the effect ofimmunosuppressive agents, or fluctuation in the natural course of ankylosing spondylitisalthough further studies are required. The regression of syndesmophytes in ankylosingspondylitis in this case raises the possibility that stem cell transplantation might contribute tothe development of a novel therapeutic strategy for treatment of the disease.     

Clinical and cytogenetic staging of chronic myeloid leukemia. Philadelphia positive

A cooperative study between clinical and cytogenetic steps in 44 patients with Ph'+ CGL is reported in order to verific the usefulness of the cytogenetic screening for the diagnosis and the right classification of the patients. The study of the clinical steps is carried out on the basis of the parameters suggested by Tura and coll.; in the one of the cytogenetic steps Sandberg classification modified by the Authors is adopted. In 40 cases the comparison shows a marrow correspondence between clinical and cytogenetic steps. In fact the overage survival in the classical true steps of the disease is almost the sance in the 1st and 2nd step. In the 3rd step the survival is strongly reduced meaning that the more chromosome alterations are observed the more survival is reduced.     

Twenty-year cytogenetic and molecular follow-up of a patient with ring chromosome 15: a case report

ABSTRACT: INTRODUCTION: Ring chromosome 15 is a rare disorder, with only a few over 40 cases reported in the literature. There are only two previous reports of cases where patients with ring chromosome 15 have been followed-up. CASE PRESENTATION: We report here on the 20-year clinical and cytogenetic follow-up of a patient with a ring chromosome 15. Our patient, a Caucasoid Asian woman, presented with short stature, microcephaly, minor dysmorphic features, hyperextensible knees, generalized hirsutism, cafe-au-lait and small hypochromic spots spread over her face and the front of her chest and abdomen, dorsolumbar scoliosis and mild intellectual disability. She was followed-up from the age of eight to 28 years. When she was 27 years old, she was reported by her mother to present with compulsive overeating and an aggressive mood when challenged. Karyotyping revealed that the majority of her cells harbored one normal chromosome and one ring chromosome. Silver staining revealed the presence of the nucleolar organizer region in the ring chromosome. Ring loss and/or secondary aberrations exhibited a slight increase over time, from 4.67% in 1989 to 7.67% in 2009, with the presence of two monocentric rings, cells with interlocked rings, a dicentric ring, and broken or open rings. A genome-wide array technique detected a 5.5Mb deletion in 15q26.2. CONCLUSIONS: We observed that some phenotypic alterations in our patient can be associated with gene loss and haploinsufficiency. Other features may be related to different factors, including ring instability and epigenetic factors.     

Two different point mutations in ABL gene ATP-binding domain conferring primary imatinib resistance in a chronic myeloid leukemia (CML) patient: A case report

Imatinib (Gleevec) is the effective therapy for BCR-ABL positive CML patients. Point mutations have been detected in ATP-binding domain of ABL gene which disturbs the binding of Gleevec to this target leading to resistance. Detection of mutations is helpful in clinical management of imatinib resistance. We established a very sensitive (ASO) PCR to detect mutations in an imatinib-resistant CML patient. Mutations C944T and T1052C were detected which cause complete partial imatinib resistance, respectively. This is the first report of multiple point mutations conferring primary imatinib resistance in same patient at the same time. Understanding the biological reasons of primary imatinib resistance is one of the emerging issues of pharmacogenomics and will be helpful in understanding primary resistance of molecularly-targeted cancer therapies. It will also be of great utilization in clinical management of imatinib resistance. Moreover, this ASO-PCR assay is very effective in detecting mutations related to imatinib resistance. Published: July 1, 2004.     

Minute chromosomes in a case of chronic Ph1-positive myeloid leukemia

Minute chromosomes (mins) were found in all bone marrow cells in a 62-year-old woman with Ph1 positive chronic myeloid leukemia. The cells had a range of 39 to 50 chromosomes with a mode of 46. The examined metaphases had a variety of numerical and structural chromosome abnormalities, as well as 2 to 6 minute chromosomes. Our case supports the assumption that there may be a correlation between the presence of mins in leukemias and the resistance of the cells to chemotherapy or the rapid progression of the disease.     

Concurrent chronic myelogenous leukemia and tuberculous lymphadenitis: a case report

BACKGROUND: Double pathology is uncommon. The diagnostic effort must be directed toward uncovering a disorder that can explain all the findings in a given patient. However, exceptions occur, notably in the sphere of infectious disorders. This is particularly true in the context of multiple infections in immunocompromised patients. CASE: Fine needle aspiration was performed on 2 lymph nodes in a 22-year-old male. Extramedullary hematopoiesis was seen in 1, while the other showed acellular necrosis with acid-fast bacilli. The hematologic workup revealed chronic myelogenous leukemia. CONCLUSION: Extramedullary hematopoiesis can be a cytologic clue to hematologic disorders. A search for an additional infectious disease may be in order.     

Diagnosis of unexpected acute myeloid leukemia and chronic lymphocytic leukemia: a case report demonstrating the perils of restricted panels in flow cytometric immunophenotyping

We report on the flow cytometric identification of concomitant acute myeloid leukemia and chronic lymphocytic leukemia in cytology specimens submitted with minimal clinical information. A 64-year-old man presented with fever and progressive dyspnea on exertion. Chest X-ray and computed tomography scan showed a left upper lobe pulmonary mass. Pulmonary capillary pullback specimens were collected to determine infectious verses neoplastic etiology. The pulmonary capillary pullback specimens showed atypical mononuclear cells with enlarged, slightly irregular nuclei; visible nucleoli; and basophilic cytoplasm. Flow cytometric analysis of the specimen for lymphoma was requested. Flow cytometric immunophenotypic studies showed that 78% of the cells were CD34 positive, CD45 dim positive and CD11c positive, consistent with acute myeloid leukemia. About 0. 75% of the cells expressed CD5 as well as dim CD20 and were monoclonal for kappa light chains: consistent with chronic lymphocytic leukemia/small lymphocytic lymphoma. At this time the clinician communicated a history of myelodysplastic syndrome of refractory anemia subtype. Peripheral blood was obtained for further immunophenotyping and the patient was immediately treated for his acute myeloid leukemia. This case demonstrates that a diagnostic antibody panel should allow evaluation of all cell types as per the U.S./Canadian consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry (Stewart et al.: Cytometry 30:231-235, 1997). Published 2000 Wiley-Liss, Inc.     

Breakthrough pulmonary Aspergillus fumigatus infection with multiple triazole resistance in a Spanish patient with chronic myeloid leukemia

BackgroundAn allogeneic hematopoietic cell transplantation (allo-HCT) patient presented with chronic pulmonary aspergillosis associated to pulmonary graft versus host disease (GVHD) and was treated for a long time with several antifungal agents that were administered as prophylaxis, combination therapies, and maintenance treatment. The patient suffered from a breakthrough invasive pulmonary aspergillosis due to Aspergillus fumigatus after long-term antifungal therapy.Material and methodsSeveral isolates were analyzed. First isolates were susceptible in vitro to all azole agents. However, after prolonged treatment with itraconazole and voriconazole a multiple azole resistant A. fumigatus isolate was cultured from bronchoalveolar lavage (BAL) when the patient was suffering from an invasive infection, and cavitary lesions were observed.ResultsAnalysis of the resistant mechanisms operating in the last strain led us to report the first isolation in Spain of an azole resistant A. fumigatus strain harboring the L98H mutation in combination with the tandem repeat (TR) alteration in CYP51A gene (TR-L98H). Long-term azole therapy may increase the risk of resistance selecting strains exhibiting reduced susceptibility to these compounds. However, since the isolates were genetically different the suggestion that could be made is that the resistance was not induced during the prolonged azole therapy but the patient might simply have acquired this resistant isolate from the environment, selected by the therapy.ConclusionsThese findings suggest that in all long-term treatments with antifungal agents, especially with azoles, repeated sampling and regular susceptibility testing of strains isolated is necessary as resistant isolates could be selected.     

Serum factors in chronic myeloid leukemia

Mononuclear cells from the peripheral blood of healthy test persons were cultivated in a methylcellulose medium with serum samples taken from 13 patients with chronic myeloid leukemia (CML) and with osteomyelosclerosis (OMS) as well as with serum samples of 6 healthy test persons. From evaluating the proliferation of granulopoietic cells quantitatively, conclusions were made concerning the concentrations of granulopoietic stimulating substances in these sera. In all cultures with the serum of patients the number of granulopoietic cell colonies was greater than that in cultures with the serum of normal persons. The stronger proliferation of granulopoietic precursor cells in cultures with serum of patients is seen to be due to an enhanced production of the granulocyte-macrophage colony stimulating factor (GM-CSF) by leukemic cells. The differential hemograms and curves indicating the course of leukocytes in patients are compared with the corresponding results of cultures. In patients with CML an increased output of GM-CSF will apparently influence the increase in size of the granulopoietic stem cell pool, which is evident in the steep increase of those curves indicating the course of leukocytes. In patients with OMS, however, there is a discrepancy between granulopoietic serum activity and proliferation in vivo. From these investigations the hypothesis is derived that an increased synthesis of GM-CSF in patients with CML may be one of the causes underlying hyperplastic granulopoiesis. A direct advantage of leukemic cells in proliferation cannot be derived from it.(ABSTRACT TRUNCATED AT 250 WORDS)     

Imatinib mesylate in chronic myeloid leukemia

Chronic myeloid leukemia has become a paradigm for the discovery of target therapeutic approaches in the field of onco-hematology. Recognition of the tyrosine kinase activity of the p210Bcr-Abl oncoprotein led to the development of compounds targeting against BCR-ABL and then controlling the leukemic proliferation. Imatinib mesylate, one of the first tyrosine kinase inhibitors developed, was found effective and safe. According to five-years experience with this drug, it is recommended that the golden standard for initial treatment of newly diagnosis chronic myeloid leukemia patients should be 400 mg Imatinib daily. In this brief review, we discuss the current tools for the effective management of chronic myeloid leukemia with Imatinib, providing the updated results of IRIS and RIGHT clinical trials and then the suggestions how Imatinib-treated patients should be monitored.     

Eosinophilia in a patient with cyclical vomiting: a case report

BACKGROUND: Eosinophilic gastritis is related to eosinophilic gastroenteritis, varying only in regards to the extent of disease and small bowel involvement. Common symptoms reported are similar to our patient's including: abdominal pain, epigastric pain, anorexia, bloating, weight loss, diarrhea, ankle edema, dysphagia, melaena and postprandial nausea and vomiting. Microscopic features of eosinophilic infiltration usually occur in the lamina propria or submucosa with perivascular aggregates. The disease is likely mediated by eosinophils activated by various cytokines and chemokines. Therapy centers around the use of immunosuppressive agents and dietary therapy if food allergy is a factor. CASE PRESENTATION: The patient is a 31 year old Caucasian female with a past medical history significant for ulcerative colitis. She presented with recurrent bouts of vomiting, abdominal pain and chest discomfort of 11 months duration. The bouts of vomiting had been reoccurring every 7-10 days, with each episode lasting for 1-3 days. This was associated with extreme weakness and cachexia. Gastric biopsies revealed intense eosinophilic infiltration. The patient responded to glucocorticoids and azathioprine. The differential diagnosis and molecular pathogenesis of eosinophilic gastritis as well as the molecular effects of glucocorticoids in eosinophilic disorders are discussed. CONCLUSIONS: The patient responded to a combination of glucocorticosteroids and azathioprine with decreased eosinophilia and symptoms. It is likely that eosinophil-active cytokines such as interleukin-3 (IL-3), granulocyte macrophage colony stimulating factor (GM-CSF) and IL-5 play pivotal roles in this disease. Chemokines such as eotaxin may be involved in eosinophil recruitment. These mediators are downregulated or inhibited by the use of immunosuppressive medications.     

Blast crisis in chronic myeloid leukemia

Although the worst prognosis among acute forms of leukemia is persistently attributed to the blast crisis of chronic myeloid leukemia, a therapeutic nihilism seems to us to be unreasonable. Even in the developing stage of a blast crisis we consider an aggressive chemotherapy to be justified particularly in younger patients. In this connection, value and necessity of supporting of therapy are especially emphasized. Remissions can be achieved in about one third of patients during the blast crisis of CML. As in other forms of tumour therapy, the initial status, age, and secondary diseases have to be taken into account and a careful, individual therapy planning has to be made. For the future there is the hope that the increasing possibilities of differentiating blasts will allow more systematic therapeutic conclusions to be made. According to the present knowledge the greatest hopes for achieving long-term remissions or even healings can, in our opinion, be expected by bone-marrow transplantation.