Leukemic hypopyon in acute myelogenous leukemia

We encountered a patient with acute myelogenous leukemia (AML) who developed leukemic hypopyon. Leukemia initially spread into the pharynx, gingiva, lymphnode, and bone marrow. He achieved complete remission after chemotherapy but developed blurred vision and hypopyon. Anterior chamber paracentesis disclosed leukemic infiltration of the anterior chamber. Infiltration of the central nervous system also occurred. He received systemic chemotherapy, intrathecal chemotherapy, and local chemotherapy. However, he did not achieve prolonged remission. These findings suggest that these chemotherapy treatments have an inadequate effect for AML with anterior chamber infiltration. This rare complication is associated with extramedullary infiltration of leukemia. Received: 13 September 1999 / Accepted: 23 December 1999     

High-dose methotrexate in the treatment of adult acute lymphoblastic leukemia

 The application of high-dose treatment elements has an increasing importance in the therapy of acute lymphoblastic leukemia (ALL). High-dose methotrexate (HDMTX) has been introduced in clinical trials more than 20 years ago, since it has several theoretical advantages compared to conventional dose methotrexate. These trials revealed that the efficacy and toxicity of HDMTX depends on features such as dose level, infusion time, combination regimen and schedule of leucovorin rescue. Particularly the application of controlled leucovorin rescue and improved supportive care enabled the application of increasing doses of HDMTX in the treatment of childhood and adult ALL within a variety of schedules and at dose levels mostly ranging between 0.5 g/m² and 5.0 g/m². In childhood ALL, first devised to replace CNS irradiation in the prophylaxis of CNS relapse HDMTX has contributed to the reduction of bone marrow relapses particularly in low risk B-lineage ALL. In addition it proved to be an effective therapy element for prophylaxis and treatment of CNS disease. At least in low risk ALL CNS irradiation could be safely replaced by repeated cycles of HDMTX with additional intrathecal therapy. In adult ALL only few of the succesful treatment approaches with HDMTX have been investigated up to now. The results indicate that HDMTX has a beneficial effect with regard to overall outcome in adult B-lineage ALL. It provides effective CNS prophylaxis in combination with intrathecal therapy. In mature B-ALL HDMTX proved to be one of the most effective treatment elements and contributed to an impressive improvement of outcome in this subgroup. For T-ALL however sufficient data do not exist either in childhood or in adult ALL. Since HDMTX is an effective treatment element with manageable acute and long-term toxicity, its role in the management of adult ALL should be explored more intensively. Received: 15 January 1996 / Accepted: 17 January 1996     

Adjuvant therapy with rhGM-CSF for the treatment of Blastoschizomyces capitatus systemic infection in a patient with acute myeloid leukemia

 We report a patient with acute myeloid leukemia and Blastoschizomyces capitatus sepsis who developed multiple abscesses when neutrophils recoved. The patient did not respond to antifungal therapy and her clinical condition showed an improvement only after rhGM-CSF was added to the treatment. Received: 30 November 1995 / Accepted: 4 April 1996     

Chronic lymphocytic leukemia presenting as acute urinary retention due to leukemic in filtration of the prostate

 Leukemic infiltration of the prostate is unusual. Acute retention of urine as the first clinical manifestation of an unsuspected, asymptomatic chronic lymphocytic leukemia (CLL) is found only in sporadic case reports. This report documents a case of CLL in a 65-year-old man presenting with acute urinary retention. The literature pertinent to this topic is briefly discussed. Received: 27 March 1996 / Accepted: 21 May 1996     

Aspergillus fumigatus endophthalmitis in a patient with acute myeloid leukaemia

A 55-year-old patient developed progressive loss of vision in one eye following induction chemotherapy for acute myeloid leukaemia (AML). Aspergillus fumigatus was cultured from vitreal aspirates. The patient was treated with intravenous and intravitreal amphotericin B but suffered complete loss of vision in her right eye. We believe this is the first report of culture-proven Aspergillus fumigatus endophthalmitis in a patient treated for a haematological malignancy.     

Hemolytic-uremic syndrome as a presenting form of acute lymphocytic leukemia

 We report an 8-year-old girl who presented with hemolytic–uremic syndrome (HUS) as the onset manifestation of acute lymphocytic leukemia (ALL). The patient was admitted to the hospital for renal failure, thrombocytopenia, and anemia during a HUS outbreak. She was discharged 2 weeks later with normal renal function. One month later the girl presented with clinical and laboratory signs consistent with a diagnosis of ALL. The short time interval between HUS and ALL suggests that HUS was probably an early manifestation of acute leukemia. Received: 13 April 1999 / Accepted: 9 February 2000     

Origin of stroma cells in long-term bone marrow cultures from patients with acute myeloid leukemia

 Bone marrow stroma cells from patients with acute myeloid leukemia (AML) display a variety of functional abnormalities. In order to determine whether this is related to an imbalance in the proportion of different stroma cell types or to integration of leukemic progeny into the regulatory cell network, stroma layers were established in mycophenolic acid-treated long-term marrow cultures from 16 patients with AML and 42 controls and analyzed by means of simultaneous membrane immunofluorescence and interphase cytogenetics. Macrophages were identified by CD14 expression, fibroblasts by staining with the AS02 antibody, and malignant cells by leukemia-specific numerical chromosome aberrations, including monosomy 7 and trisomy 8. Compared with normal controls, there was a slight decrease in the proportion of stroma fibroblasts (52±27% versus 77±5%) in 10-week-old cultures from patients with AML. Two of five AML patients with trisomy 8 and both patients with monosomy 7 had evidence of leukemic stroma cells. Most malignant cells were CD14+ macrophages (3.8–98.1% of all CD14+ cells), but some were AS02+ (2.8–5.2%). AML stroma layers showed a reduced capacity to support the growth of normal hematopoietic cells in standard two-stage long-term cultures, but this was unrelated to the presence or absence of leukemic stroma elements. In conclusion, AML populations vary with respect to their ability to produce a malignant microenvironment. Functional defects in the hematopoietic microenvironment, however, are not limited to AML patients with cytogenetically abnormal stroma cells, but extend to cases without evidence of malignant stroma cells. Received: December 9, 1998 / Accepted: February 2, 1999     

MTS1 expression and prognosis in acute myeloid leukemia

 MTS1, a tumor supressor gene located on chromosome 9p21, has been shown to be altered in a number of human tumor cell lines, primary solid tumors, and leukemias. In this study we found low expression of MTS1 in lymphocytes from seven of nine healthy donors, but in none of eight granulocyte samples from the same controls, suggesting a physiological role of MTS1 in peripheral blood cells capable of proliferation, but not in end-stage differentiated cells. We detected MTS1 mRNA expression in 38 of 57 patients (66%) with acute myelogenous leukemia (AML) treated in a standardized clinical protocol. No deletion of the MTS1 gene was found in any of the AML samples tested. There was no significant association between expression of MTS1 and response to therapy, progression-free, or overall survival. Except for a negative correlation between MTS1 level and leukocyte count at diagnosis (p=0.03), there was also no association with any of the known prognostic parameters in AML. We conclude that MTS1 shows a significantly higher expression in leukemic than in normal peripheral blood cells, that deletion of MTS1 is not a frequent event in AML, and that its expression is not significantly correlated with outcome of the disease. Received: 7 April 1997 / Accepted: 18 August 1997     

Recurrent idiopathic iridocyclitis after autologous peripheral blood stem-cell transplantation followed by G-CSF administration for acute lymphoblastic leukemia

 We describe a patient who experienced a recurrence of idiopathic iridocyclitis on day 12 after autologous peripheral blood stem-cell transplantation (auto-PBSCT) followed by G-CSF administration for acute lymphoblastic leukemia (ALL). Autologous SCT has been reported to be effective and safe in achieving dose intensification of chemotherapeutic drugs for the treatment of hematopoietic malignancies, but its therapeutic effect on autoimmune diseases is not definite. The findings from the present case suggest that auto-PBSCT followed by G-CSF administration for patients with a history of some kind of autoimmune disorders may induce exacerbation or recurrence of its symptoms after hematopoietic recovery. Received: 9 April 1999 / Accepted: 4 October 1999     

Fatal pulmonary hemorrhage in patients with acute leukemia and fulminant pneumonia caused by Stenotrophomonas maltophilia

 Pulmonary hemorrhage is a rare cause of death in patients with acute leukemia. Within a 3-month period we observed three such cases, all of which were associated with the gram-negative opportunistic pathogen Stenotrophomonas maltophilia. Since fatal lung bleeding had previously not been observed in conjunction with this organism, we collected the data from all patients with documented S. maltophilia infections or colonizations of the past year and analyzed the risk factors for a lethal outcome. A total of eight patients were identified. In the three patients with fatal hemorrhage, the interval between first complaints (chest pain, cough, fever) and death from lung bleeding was 36–72 h. A fourth patient with acute leukemia died of nonhemorrhagic respiratory failure 9 days after developing S. maltophilia-associated pneumonia. All four patients had received intensive chemotherapy and were severely neutropenic and thrombocytopenic. Such a combination of predisposing factors was not observed in the four patients with nonfatal infections or colonizations. Pulsed-field gel electrophoresis demonstrated that the infections were unrelated. S. maltophilia was also isolated from a faucet in a patient's room, but the strain isolated was genetically different from the strain causing the patient's pneumonia. Our data suggest that severe bone marrow aplasia and a recent history of intensive chemotherapy are predisposing factors for the development of fulminant hemorrhagic S. maltophilia pneumonia. Since some of the infections and colonizations developed despite prophylactic administration of antibacterial agents with documented in vitro activity against the pathogen and none was controlled by such agents, it is clear an efficient treatment strategy needs to be developed. Received: 23 January 1997 / Accepted: 24 February 1997     

Disseminated intravascular coagulation in acute lymphoblastic leukemia at presentation and in early phase of remission induction therapy

 A high frequency of disseminated intravascular coagulation (DIC) in adult acute lymphoblastic leukemia (ALL) has been reported; however, its clinical relevance and characteristics have not been fully determined. We studied 67 adults with newly diagnosed ALL between 1982 and 1996 to clarify these questions. DIC was diagnosed in ten of 64 patients (16%) who underwent coagulation study at presentation and in 14 of 40 patients (35%) screened for DIC within 7 days after starting remission induction therapy. Overall, 24 of 67 patients (36%) had DIC during this period. Hemorrhagic symptoms were generally mild, while two patients required red blood cell transfusions. Patients who developed DIC had higher white blood cell counts and more frequently a palpable spleen than those who did not. There was no difference in age, French-American-British subtype, karyotype, immunophenotype, lactate dehydrogenase level, percentage of blasts in bone marrow, or frequency of lymphadenopathy or hepatomegaly between patients who had DIC and those who did not. Fibrinolysis tended to be milder in DIC complicating ALL than in that complicating acute promyelocytic leukemia; however, there was no difference in other coagulation parameters between these two subtypes. An etiological link between CD34 expression in common ALL patients and DIC was suggested. Received: December 8, 1997 / Accepted: March 13, 1998     

Immunophenotype and clinical characteristics of CD45-negative and CD45-positive childhood acute lymphoblastic leukemia

 To evaluate the expression pattern of the leukocyte common antigen CD45 in acute leukemias and to investigate whether the lack of CD45 expression in childhood acute lymphoblastic leukemia (ALL) is associated with other immunophenotypic features and a distinct clinical behavior, we have carried out extensive immunophenotypic analyses of bone marrow and peripheral blood samples from 638 patients with childhood B-cell precursor (n=529) or T-lineage ALL (n=109). All 638 patients were enrolled in the German ALL-BFM 90 and ALL-BFM 95 trials. CD45 was detected on the surface of childhood ALL cells (cut-off ≥20% positive cells) in only 88.7% (n=566) of all cases. Among 529 patients with childhood B-cell precursor ALL, 12.9% (n=68) did not express CD45, compared with only 3.7% (n=4) of patients with childhood T-lineage ALL (p<0.001). In the B-cell precursor ALL subtypes, the highest frequency of CD45- cases (15.1%) was observed in common ALL (56/372) compared with only 7.2% in pro-B ALL (3/41) and 7.8% in pre-B ALL (9/116). Assessment of clinical parameters (age, organ enlargement, WBC, etc.) and event-free survival did not reveal significant differences between CD45- and CD45+ patients. Myeloid antigen coexpression was not correlated with CD45 expression. The mean percentage of antigen expression for CD34, CD10, TdT, CD22, and CD24 was significantly higher in children with CD45- B-cell precursor ALL than in those with CD45+ B-cell precursor ALL. In 28 patients with B-cell precursor ALL, cell cycle analyses of freshly isolated leukemic cells were performed with propidium iodide (PI) staining and flow-cytometric analysis. The percentage of cells in S-phase was inversely correlated to the percentage of CD45+ cells (r=-0.48, p<0.05). With two-parameter analysis of CD45-fluorescein isothiocyanate (FITC)- and PI-stained cells in nine patients with a percentage of CD45+ cells between 40 and 60%, two populations were distinguishable in a single patient. It was shown that the CD45- subpopulation had a higher percentage of cells in S-phase than the CD45+ subpopulation (10.7±4.0 vs. 2.7±1.8, p<0.007). We conclude that the lack of CD45 expression contributes to the identification of a distinct functional and immunological subgroup of B-cell precursor ALL, but that it has no significant impact on clinical behavior or on therapy outcome in childhood ALL. Received: February 18, 1998 / Accepted: May 26, 1998     

Bulky lymphadenopathy in acute myeloid leukemia

 Two cases of acute myeloid leukemia (AML) presenting with bulky adenopathy are reported. Both patients were febrile at admission and showed massive and diffuse lymph node involvement, hepatomegaly, and splenomegaly. Erythematopapular leukemic skin lesions were present in one case at the onset and developed in the other at the time of relapse. Anemia, thrombocytopenia, and moderate leukocytosis were present in both. The presence of immature cells in peripheral blood and bone marrow allowed a rapid diagnosis of AML, FAB M1, in one patient. In the other case, owing to the paucity of immature cells in peripheral blood and bone marrow, lymph node biopsy with histology, imprint cytology, and immunocytochemistry were essential for the diagnosis (AML, FAB M2, with trilineage dysplasia and basophilic involvement). Both patients achieved complete remission (CR), followed by an early relapse 3 months later. They underwent allogeneic bone marrow transplantation (BMT) from HLA identical siblings. One patient is actually alive and in CR at 6 months after BMT; the other patient showed a leukemic regrowth after transplantation and died 4 months later. Received: December 8, 1997 / Accepted: April 29, 1998     

Sometimes it really is appendicitis: case of a CML patient with acute appendicitis

 We report on the case of a 24-year-old white man with a history of chronic leukemia treated with unrelated bone marrow transplantation and chemotherapy who was correctly diagnosed with appendicitis rather than typhlitis. The approach to diagnosing an acute abdomen in the leukemic patient is discussed, with particular focus on appendicitis vs. typhlitis. A focused CT scan proved to be instrumental in making the correct diagnosis of appendicitis in our patient. The literature on this topic for the past 30 years is reviewed. The purpose of our report is to demonstrate that despite the recent trend toward diagnosing RLQ pain as typhlitis which requires medical management, there are still instances where it 'really is' appendicitis. Appendicitis, therefore, must always be ruled out in the leukemic patient. Received: December 29, 1997 · Accepted: April 16, 1998     

Progression of a myelodysplastic syndrome to pre-B acute lymphoblastic leukemia: a case report and cell lineage study

 The evolution of acute lymphoblastic leukemia from a myelodysplastic syndrome is a very uncommon event. We describe a 46-year-old man in whom refractory anemia with excess blasts (RAEB) evolved to a pre-B acute lymphocytic leukemia. Trisomy 8 was one of the cytogenetic abnormalities in the dysplastic clone and was detected in both peripheral blood and bone marrow smears of interphase cells by the fluorescence in situ hybridization (FISH) technique. Using a chromosome 8 centromeric specific DNA probe we identified the trisomy 8 to be present in lymphoblasts, erythroid precursors, myeloblasts, promyelocytes, myelocytes, metamyelocytes, granulocytes, and monocytes. Our case supports the hypothesis that in MDS the pluripotent precursor cell is affected, and we examine the potential role of FISH for the study and follow-up of some hematological diseases. Received: 9 October 1995 / Accepted: 21 December 1996     

Thrombotic events are not exclusive to the remission induction period in patients with acute lymphoblastic leukemia: a report of two cases of cerebral sinus thrombosis

 It is well established that in acute lymphoblastic leukemia (ALL) patients l-asparaginase (l-Ase) provokes thrombotic events reducing coagulation inhibitors in both adults and children. A tight correlation between thrombotic and hemorrhagic complications and ALL has also been hypothesized because of the high incidence of disseminated intravascular coagulation (DIC) found during the early period of chemotherapeutic treatment apart from l-Ase. All the authors reporting on this subject, however, consider the remission induction phase of treatment the most risky, if not exclusive, for the development of a thrombotic event, in particular if it includes the administration of l-Ase. We report here two cases of ALL patients who experienced a cerebral sinus thrombosis in a later phase of treatment, demonstrating that the thrombotic risk is surely exacerbated by chemotherapy but is not exclusive to the remission induction period. Received: 1 April 1997 / Accepted: 11 June 1997     

T-cell lineage acute lymphoblastic leukemia with chromosome 5 abnormality in a patient with Crohn's disease and lipoid nephrosis

 We describe a 17-year-old patient with a documented history of Crohn's disease (CD) and of minimal-change nephrotic syndrome (MCNS) in whom a diagnosis of T-cell acute lymphoblastic leukemia (ALL) was made. The diagnosis of ALL was established by morphological examination of bone-marrow aspirates and confirmed by means of immunophenotypic analysis showing the involvement of T-cell lineage leukemic cells. The lymphoid clone showed a karyotypic abnormality involving the long arm of chromosome 5 in a translocation (5;6). Few cases of CD complicated by ALL have been previously reported. The present one is the first case combining CD and ALL in a patient with a past history of MCNS. This raises the possibility of a relationship among those diseases. The possible mechanisms for such a relationship are discussed here. Received: June 25, 1999 / Accepted: September 9, 1999     

Occurrence of T-cell lymphoma in a patient with acute myelogenous leukemia

 We describe a patient with AML with a monocytic component who developed a T-lymphoblastic lymphoma. Lymphoma was diagnosed 9 months following AML diagnosis. To our knowledge, this is the first report of phenotypically documented T-cell lymphoma following AML. The questions relating to the pathogenesis of the two malignancies are discussed. Received: 22 January 1996 / Accepted: 12 April 1996