Prevention of infections in a case with myelodysplastic syndrome by an intermittent subcutaneous administration of G-CSF

An 83-year-old male was admitted to our hospital because of pancytopenia and low grade fever on April 19, 1993. On admission, hematological data were as follows: WBC 1,000/microliters with 19% neutrophils, RBC 367 x 10(4)/microliters, Hb 9.5 g/dl and platelets 6.7 x 10(4)/microliters. Bone marrow examination revealed 6.6% myeloblasts and 33.5% erythroblasts. Morphological abnormalities included hypersegmentation, degranulation and pseudo-Pelger's nuclear anomaly in neutrophils. Based on these findings the diagnosis of refractory anemia with excess of blasts (RAEB) of the myelodysplastic syndrome (MDS) was made and therapy with low dose Cytarabine (Ara-C) was initiated in April 1993. The patient had two episodes of severe pneumonia in June and July. Therefore, 75 micrograms/day of G-CSF was given in addition to antibiotic therapy for the second episode of infection in July. Thereafter the severe infection subsided, and G-CSF administration was switched to an intermittent schedule (75 micrograms twice a week) since September. Cytarabine ocfosfate (100 mg/day) was added for 10-14 days at interval 1-2 months from October,1993. He has been well with no episode of infection for more than two year. One major concern regarding the clinical application of G-CSF in MDS patients is related to the possible stimulation of leukemic cell proliferation. Frequent hematological monitoring is necessary in patients with RAEB who are prone to develop acute myeloid leukemia. However, we administered G-CSF at a relatively low dose twice a week for over two year and could successfully prevent infections without inducing the leukemic changes.     

CD14-positive and nonspecific esterase-positive neutrophils in a patient with refractory anemia with excess of blasts in transformation

A 34-year-old man was admitted with lumbago and anemia in November 1992. Hematological examination revealed an Hb 9.2g/dl, WBC count 13,500 microliters (33% blasts), and monocyte count 3,400/microliters. Bone marrow examination showed hyperplasia with dysplasia in trilineage blood cells and increased blasts (21.8%). A diagnosis of refractory anemia with excess of blasts in transformation (RAEB in T) was made. Cytochemical examination revealed the neutrophils in the peripheral blood were 66.5% positive for alpha-naphthyl butyrate esterase inhibited by sodium fluoride, 4.0% positive for peroxidase and 75% positive for alkaline phosphatase. The results of immuno-alkaline phosphatase stainings (avidin biotin alkaline phosphatase complex method) of neutrophils were as follows; CD16 (94.5%), CD24 (91.0%), CD13 (93.0%), CD14 (52.5%), CD33 (39.0%), CD36 (16.5%), HLA-DR (17.0%). These neutrophils exhibited monocyte-specific features and failed to show characteristics of neutrophils.     

Successful emergency operation for massive hemorrhage due to jejunal angiodysplasia after intensive chemotherapy in a patient with refractory anemia with excess of blasts

A 59-year-old man was referred to our hospital because of pancytopenia. Peripheral blood examination showed a WBC of 1,500/microliters with 2% blasts, Hb 8.1 g/dl and a platelet count of 4.1 x 10(4)/microliters. A bone marrow aspiration revealed hyperplasia with proliferation of blasts (15.7%) and myelodysplasia. Chromosome analysis revealed multiple aberrations, including -5, -7, +8. The patient was given a diagnosis of refractory anemia with excess of blasts (RAEB) and treated with combination chemotherapy. Agranulocytosis and high fever remained after chemotherapy, and abdominal pain and diarrhea developed. An abdominal X-ray film and computed tomography scan demonstrated dilated small bowel, thickness of the bowel wall, and ascites. A diagnosis of neutropenic enterocolitis was given. During the WBC recovery period from nadir, massive hematochezia developed in the patient. Angiography detected the leakage of contrast medium from a peripheral region of the first jejunal artery into the jejunal lumen. A partial resection of the jejunum was thus performed, and a histological examination revealed the presence of irregularly dilated blood vessels in the submucosal layer. These findings were consistent with the features of angiodysplasia, and indicate that angiodysplasia should be considered one cause of intestinal hemorrhage in elderly patients during intensive chemotherapy.     

Acute myelogenous leukemia (FAB AML-M1) in the setting of HIV infection and G-CSF therapy: a case report and review of the literature

Although hematologic dysplasia is common in HIV disease, evolution to AML is unusual. We report a case of AML in a patient with stage-C3 AIDS who had been previously treated with granulocyte colony-stimulating factor (G-CSF). This 41-year-old black man presented with pancytopenia (Hg 8.6 g/dl, Hct 24.3%, platelets 16,000/mm3, WBC 0.6 x 10(3)/mm3) and hemoptysis. His peripheral smear manifested 19% blasts. His bone marrow biopsy was hypocellular (20%) with greater than 90% blasts, which were positive for myeloperoxidase and Sudan black B. The blasts were negative for nonspecific esterase. Immunophenotypic analysis by flow cytometry showed the majority of cells to be of myeloid lineage, expressing CD13, and CD45 at low intensity. In addition, there was aberrant expression of CD2 and no expression of CD14 or CD4. The diagnosis of AML-FAB-M1 was made. The patient refused chemotherapy. Of the rare cases of AML in HIV patients previously reported in the literature, the majority were of the monocytic or myelomonocytic subtype. This case is of special interest because of prior G-CSF therapy. In this setting, the relationship between HIV, G-CSF, and subsequent AML is controversial.     

Neutrophilic myelofibrosis; a case report

A 53-year-old male was admitted to our hospital with abdominal pain. Physical examination revealed marked splenomegaly. The white blood cell count increased to 5.8 x 10(4)/microliters. Bone marrow biopsy showed hypercellularity with a moderate increase in reticulin fiber. Chromosomal analysis showed 47, XY, +9q-, -9q- without Ph1 chromosome and bcr-abl rearrangement. MCNU therapy was successful in reducing the white blood cell count and splenomegaly. It is likely that the diagnosis of our patient is compatible with the neutrophilic myelofibrosis described by Stewart, et al.     

Case report: reversal of severe leukopenia by granulocyte colony-stimulating factor in anorexia nervosa

Recent attempts to reduce weight by patients with anorexia nervosa have sometimes led to life-threatening hematologic complications. This report describes an instance in which a patient with anorexia nervosa and pancytopenia drastically improved with treatment that included administration of granulocyte colony-stimulating factor. The patient had lost 27 kg of body weight within 8 months. Even after admission, the blood cell count continued to decrease rapidly as follows: platelet, from 244 x 10(3)/microliters to 44 x 10(3)/microliters; erythrocyte, from 4.04 x 10(6)/microliters to 2.58 x 10(6)/microliters; and leukocyte, from 4.8 x 10(3)/microliters to 1.6 x 10(3)/microliters (granulocyte, 0.8 x 10(3)/microliters). Complications included pneumomediastinum, pneumothorax, purpura, petechiae, hepatomegaly, fever, gangrenous stomatitis, and somnolence. Bone marrow aspiration disclosed absence of fat cells, marrow hypoplasia, and infiltration of the mature lymphocytes. Intravenous hyperalimentation, blood transfusion, gamma-globulin, and antibiotics were administered, but leukopenia and fever remained. However, administration of recombinant human granulocyte colony-stimulating factor dramatically reversed the leukopenia and fever. With careful nutrition therapy, the patient's blood cell count and bone marrow normalized by the time of discharge. It was concluded that severe hematologic disorders may occur in patients with anorexia nervosa, and advanced treatment may be required to save the patient's life.     

Refractory anemia with excess myeloblast in transformation induced remission by combined oral administration of cytarabine ocfosfate and 6-mercaptopurine

A 55-year-old female presented with sore throat and slight fever. The patient was admitted to our hospital on December 13, 1993. Full blood count showed hemoglobin 10.7 g/dl, white cell count 960/microliters (neutrophils 14%, lymphocytes 82%, blasts 2%) and platelets 13,000/microliters. Bone marrow examination showed hypocellularity with 4.5% of myeloblast positive for peroxidase. The bone marrow specimens on Dec. 20 showed 15.5% of myeloblasts, some of which had Auer rods. These findings led to the diagnosis of refractory anemia with excess myeloblast in transformation (RAEB-T) of French-American-British Cooperative Group. The patient was transfused and treated with cytarabine ocfosfate (SP-AC) (100 mg tid) and 6-mercaptopurine (50 mg tid) for 14 days. During chemotherapy she complained of nausea and anorexia, but they were managed easily with medication. On Feb. 7, 1994, forty-two days after the start of administration, peripheral blood and bone marrow aspirate were compatible with a complete remission. Although complete remission was sustained with courses of chemotherapy for 4 months, relapse occurred and the patient died of septicemia on August 29, 1994 after induction failure. Observation suggested that oral SPAC in combination with 6-mercaptopurine had a good antileukemic effect on the myelodysplastic syndrome. However, the duration response was short, and further improvement of the therapy is needed.     

Effective splenectomy in a patient with HIV-associated thrombocytopenia

A 31-year-old man presented with a 3-month history of petechial hemorrhages. Physical examination revealed no splenomegaly. The patient's platelet count was 1.0 x 10(9)/l and bone marrow aspiration showed an elevated number of megakaryocytes. A diagnosis of HIV-associated thrombocytopenia was made on the basis of HIV seropositive results. The CD4 cell count was 400 x 10(6)/l. No opportunistic infections indicating AIDS were detected. Initially the patient was treated with predonisolone, but showed only a transient response. He also failed to respond to zidovudine, lamivudine, or indinavir. Following splenectomy, however, his platelet count rose above 80 x 10(9)/l (normal level: 150-350 x 10(9)/l).     

Acute transformation of chronic myelomonocytic leukemia with t(1;3) (p36;q21) abnormality

A 66-year-old man was given a peripheral blood test because of low grade fever. Leukocytosis was detected, and the blood and bone marrow findings were consistent with those of chronic myelomonocytic leukemia. Three months later the hematological findings were: WBC 58,800/microliter (19% blastoid cells, 22% monocytes), Hb 9.0 g/dl, and a platelet count of 116 x 10(4)/microliters. A bone marrow examination revealed the presence of 52.6% blastoid cells and dysmegakaryocytopoiesis, including micromegakaryocytes. Serum and urinary lysozyme levels were elevated. Karyotypic analysis detected t(1; 3) (p36;q21), but not major bcr/abl mRNA. The patient was given a diagnosis of acute transformation of chronic myelomonocytic leukemia. Despite treatment, he died about 3 months later. t(1;3) is occasionally observed in cases of myelodysplastic syndrome (MDS) and leukemia. Patients with t(1;3) often exhibit dysmegakaryocytopoiesis; furthermore, acute leukemia develops more readily in those who also have MDS. Cases of long-term survival are rare.     

Bone marrow mononuclear cell count does not predict neutrophil and platelet recovery following autologous bone marrow transplant: value of the colony-forming unit granulocyte-macrophage (CFU-GM) assay

The common use of the marrow autograft mononuclear cell (MNC) count derives from positive correlative studies following allogeneic transplantation and from earlier conflicting data regarding the value of the bone marrow autograft colony-forming unit granulocyte-macrophage (CFU-GM) assay for prediction hematologic recovery after ABMT. We conducted a retrospective analysis at our institution to determine whether autograft CFU-GM levels predict engraftment of neutrophils and platelets after ABMT in heavily pretreated patients with hematologic malignancies. Between 1 January 1993 and 1 March 1995, 58 heavily pretreated patients received only marrow cells as the autograft product. Patients with Hodgkin's disease (n = 25), acute myeloid leukemia (n = 19), and non-Hodgkin's lymphoma (n = 14) underwent intensive therapy with etoposide and melphalan. Unpurged marrow containing a minimum of 1.5 x 10(8)/kg (range: 1.5-4.8) was infused. Median time to an absolute neutrophil count > or = 0.5 x 10(9)/L was 21 days (range 10-270) and median time to a platelet count > or = 20 x 10(9)/L independent of transfusions was 44 days (range 13-317). There was no correlation between autograft MNC count and neutrophil or platelet engraftment. However, a correlation between autograft CFU-GM and both platelet and neutrophil recovery was demonstrated with a threshold CFU-GM of 3 x 10(4)/kg; delayed neutrophil recovery was observed in 79% of patients below this threshold compared to only 9% in those with an autograft CFU-GM level of more than 3 x 10(4)/kg (p = 0.0001). Similarly, platelet recovery was delayed in 76% of patients below, and 20% of those above this threshold (p = 0.003). We conclude that marrow autograft CFU-GM is predictive of engraftment of both platelets and neutrophils in heavily pretreated patients after ABMT for hematological malignancies.     

Ischemic stroke in the elderly. Role of the common factor V mutation causing resistance to activated protein C

Twenty-one previously untreated multiple myeloma (MM) patients and 10 previously treated patients with refractory or relapsed disease received two or three cycles of intermediate-dose melphalan (70 mg/m2) (IDM), administered intravenously every 6 weeks. Seven previously untreated patients received three and all other patients received two courses of IDM. The objective of the study was to reduce the toxicity of high-dose melphalan (140 mg/m2) (HDM) while maintaining its cytotoxic efficacy and secondly to ensure the possibility of collecting sufficient numbers of peripheral blood stem cells (PBSC) for transplantation. 18 (85%) previously untreated patients responded, of whom four achieved CR (18%). In addition five out of 10 previously treated patients with refractory or relapsed disease responded although bone marrow toxicity in this category was a major drawback. Toxicity was moderate, consisting of alopecia and moderate bone marrow suppression: the granulocyte count dropped below 0.5 x 10(9)/l and platelets below 25 x 10(9)/l for a median of 8 and 6 d, respectively. No serious infections occurred and the majority of patients attended the out-patient clinic. In 12/14 previously untreated patients sufficient peripheral blood CD34+ cells for harvest were present in the repopulation phase after the first IDM. In nine patients peripheral blood stem cells were collected and eight patients have undergone successful transplantation. Repeated IDM followed by filgrastim is highly effective in untreated MM and may be safely administered to reduce tumour load prior to PBSC collection. Autologous stem cells harvested after repeated IDM have a full long-term repopulating capacity.     

A prospective study of the cold response of digital vessels in forestry workers exposed to saw vibration

A 49-year-old man was admitted to our hospital for investigation of splenomegaly and lymphocytosis. He had no significant past history and was not a smoker. Physical examination revealed massive splenomegaly and no palpable superficial lymph nodes. Hematological examination showed a hemoglobin concentration of 10.5g/dl, a platelet count of 9.8 x 10(4)/microliter, and a leukocyte count of 21.2 x 10(3)/microliter with 70% abnormal lymphocytes. In May-Giemsa stained blood films, the abnormal lymphocytes had round nuclei, abundant, pale cytoplasm, and slightly serrated edges. Phase-contrast microscopic and scanning electron microscopic examinations revealed many long surface villi. Tartrate-resistant acid phosphatase activity in these cells was negative. The abnormal lymphocytes had a CD5-, CD10-, CD11a+, CD11c+, CD19+, CD20+, CD22+ phenotype. These features were similar to those described for a variant form of hairy cell leukemia (HCL-Japanese variant). However, studies of Ig gene rearrangement and expression of sIg revealed a polyclonal proliferation of B cells. On the basis of these findings, this case was diagnosed as hairy B-cell lymphoproliferative disorder, a recently described condition characterized by polyclonal B-cell lymphocytosis and features resembling HCL-Japanese variant. Serological assays for antibodies against Epstein-Barr virus suggested a past infection. Splenectomy alleviated the anemia and thrombocytopenia, but not the lymphocytosis.     

Microscopic polyangiitis. Delineation of a cutaneous-limited variant associated with antimyeloperoxidase autoantibody

Identification of inexpensive and technically simple immunological tests useful in predicting the progression to AIDS in human immunodeficiency virus (HIV)-infected patients would be especially welcome in developing countries, in which 80% of HIV-infected patients reside and health budgets are low. In the current study, we evaluated CD4+ and total lymphocyte counts and the concentrations in serum of beta 2-microglobulin, p24 antigen, and immunoglobulin A (IgA) as predictors of disease progression in 74 Panamanian HIV-positive patients and 50 HIV-negative healthy individuals. Total lymphocyte and CD4(+)-cell counts for AIDS patients (1,451 +/- 811 cells/microliters, P < 0.001, and 238 +/- 392 cells/microliters, P < 0.0001, respectively and asymptomatic patients (2,393 +/- 664 cells/microliters, P > 0.05, and 784 +/- 475 cells/microliters, P < 0.001, respectively) were lower than those observed for healthy subjects (2,596 +/- 631 cells/microliters and 1,120 +/- 296 cells/microliters, respectively). The levels of beta 2-microglobulin and IgA in serum were significantly elevated in patients with AIDS (5.7 +/- 3.6mg/liter, P < 0.001, and 541 +/- 265 mg/dl, P < 0.0002, respectively) and asymptomatic infected subjects (3.4 +/- 2.1 mg/liter, P = 0.001, and 436 +/- 216 mg/dl, P < 0.0001, respectively) compared with the levels in healthy subjects (2.2 +/- 0.7 mg/liter and 204 +/- 113 mg/dl, respectively). Nonstatistically significant differences (P > 0.05) for concentrations of p24 antigen between asymptomatic infected patients (29 +/- 13 pg/ml) and AIDS patients (40 +/- 23 pg/ml) were observed. Total lymphocyte counts of 1,750 cells/microliters or less, CD4 counts of 200 cells/microliters or less, beta 2-microglobulin concentrations in serum of 4 mg/liter or higher, concentrations of IgA in serum of 450 mg/dl or higher, and the presence in serum of p24 antigen were correlated with elevated risks for developing AIDS. Monitoring both total lymphocytes and beta 2-microglobulin identified 91% of the AIDS patients; these assays may allow reductions in the annual number of CD4(+)-cell evaluations and the costs associated with monitoring both total lymphocytes and beta 2-microglobulin identified 91% of the AIDS patients; these assays may allow reductions in the annual number of CD4(+)-cell evaluations and the costs associated with monitoring the immune status of HIV-positive patients.     

A simplified method for cryopreservation of hematopoietic stem cells with -80 degrees C mechanical freezer with dimethyl sulfoxide as the sole cryoprotectant

A simplified method for cryopreservation was developed with 10% dimethylsulfoxide (DMSO) as the sole cryoprotectant without rate-controlled freezing. This method produced high recovery rate for mononucleated cells (87%) and elevated trypan blue viability (90%). Autologous peripheral blood stem cells (PBSCs) and bone marrow cells with plasma and 10% DMSO were frozen and stored in a -80 degrees C mechanical freezer. Eleven patients with solid and hematological malignancies were transplanted with autologous bone marrow or PBSCs. The median number of infused mononuclear cells (MNC) and CD34+ cells were 3.63 x 10(8)/Kg and 4.80 x 10(6)/Kg, respectively. The median number of infused post-thawing CFU-GM was 20 x 10(4)/Kg. All patients showed a rapid and sustained engraftment. The mean times to reach a neutrophil count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L were 11 and 13 days, respectively. All patients are alive and 10 in unmaintained complete remission for 3-9 months after transplantation. These results show the efficacy of this simplified cryopreservation technique that will be useful for institutions without rate-controlled freezing facilities.     

Release of polymorphonuclear leukocytes from the bone marrow by interleukin-8

Several studies have shown that interleukin-8 (IL-8) causes a rapid granulocytosis with the release of polymorphonuclear leukocytes (PMN) from the bone marrow (BM) partially responsible for the granulocytosis. This study was designed to quantitate the release of PMN from the BM by IL-8 and measure the transit time of PMN through the marrow after IL-8 administration. The thymidine analogue, 5'-bromo-2'-deoxyuridine (BrdU), was used to label dividing PMN in the marrow and follow their release into the circulation after intravenous IL-8. This allowed us to calculate the transit time of PMN through the mitotic and postmitotic pools of BM. BrdU was infused intravenously into rabbits 24 hours before IL-8 (2.5 microg/kg). IL-8 caused a rapid, transient granulocytopenia (5.9 +/- 0.4 at baseline v 0.2 +/- 0.06 x 10/9L at 5 minutes, P < .05) followed by granulocytosis (8.4 +/- 0.1 at 30 minutes, P < .05) associated with an increased number (0.3 +/- 0.1 at baseline v 1.2 +/- 0.6 x 10(9)/L at 30 minutes, P < .05) and percentage of band cells (P < .05), as well as a rapid increase in the number of BrdU-labeled PMN (PMNBrdU) in the circulation (0.09 +/- 0.05 at baseline to 1.5 +/- 0.6 x 10(9)/L at 60 minutes, P < .05). The transit time of PMN through both the mitotic and postmitotic pools of BM was not affected by IL-8. To determine the marrow compartment from which the PMN were mobilized by IL-8, we quantitated PMN movement from the hematopoietic and sinusoidal compartments into the circulation. The fraction of PMNBrdU in both compartments was higher than in the circulating blood (P < .05) and the fraction and number of PMNBrdU in the sinusoids decreased with IL-8 treatment (P < .05). We conclude that the pool of PMN residing in the BM venous sinusoids are rapidly released into the circulation after administration of IL-8.     

Autologous transplantation of mobilized peripheral blood CD34+ cells selected by immunomagnetic procedures in patients with multiple myeloma

In the use of autologous PBPC transplantation in patients with multiple myeloma, contamination of PBPC with myeloma cells is commonly observed. Enrichment for CD34+ cells has been employed as a method of reducing this contamination. In this study the reduction of myeloma cells in PBPC was accomplished by the positive selection of CD34+ cells using immunomagnetic bead separation (Isolex 300 system). PBPC were mobilized from 18 patients using cyclophosphamide (4.5 g/m2) and G-CSF (10 microg/kg/day). A median of two leukaphereses and one selection was performed per patient. The median number of mononuclear cells processed was 3.50 x 10(10) with a recovery of 1.11 x 10(8) cells after selection. The median recovery of CD34+ cells was 48% (range 17-78) and purity was 90% (29-99). The median log depletion of CD19+ cells was 3.0. IgH rearrangement, assessed by PCR, was undetectable in 13 of 24 evaluable CD34+ enriched products. Patients received 200 mg/m2 of melphalan followed by the infusion of a median of 2.91 x 10(6)/kg CD34+ cells (1.00-16.30). The median time to absolute neutrophil count >0.5 x 10(9)/l was 11 days, and sustained platelet recovery of >20 x 10(9)/l was 14 days. We conclude that immunomagnetic-based enrichment of CD34+ cells results in a marked reduction in myeloma cells without affecting engraftment kinetics.     

Proteins and cells on PEG immobilized silicon surfaces

Functional adhesion of blood and marrow leukemic cells from 14 acute myeloid leukemia patients presenting with hyperleukocytosis was evaluated by performing cytoadhesion assays on purified (extracellular matrix proteins) and non-purified supports (MRC5 fibroblastic cell line). Results, in 30-min chromium release assay, show a mean +/- S.D. adhesion to fibronectin, collagen, and laminin respectively of 30 +/- 17%, 20 +/- 13%, 25 +/- 17% for blood leukemic cells and 18 +/- 11%, 11 +/- 10%, 11 +/- 8% for marrow leukemic cells. These differences between blood and marrow cells were statistically significant (respectively P = 0.005, P = 0.01 and P = 0.002), while no difference was noted regarding adhesion to non-purified supports. The higher adhesion of blood blast cells to purified supports was observed regardless of CD34 expression. No significant difference was observed in the expression of cell surface VLA-molecules (CD29, CD49b, CD49d, CD49e, CD49f) between blood and marrow blast cells. The addition of GM-CSF or G-CSF induced increased adhesion of marrow blasts and decreased adhesion of blood blasts leading to a loss of the difference between blood and marrow cells. In a 60-min chromium release assay, marrow blasts adhered even more than blood leukemic cells to fibronectin. In contrast, marrow blasts from 'aleukemic' acute myeloid leukemia patients did not show any modification regarding their adhesion to extracellular matrix proteins when co-cultured with growth factors.     

Primary human herpes virus 6 infection transmitted from donor to recipient through bone marrow infusion

An 8.5-month-old boy with Wiskott-Aldrich syndrome received a sibling matched bone marrow transplant from his healthy non-identical twin brother. The donor had primary human herpes virus 6 (HHV-6) infection around the time of bone marrow donation. The recipient had hepatitis in the first week and then developed fever and rash on day 18. Skin biopsy was shown to have HHV-6 antigen and his peripheral blood leukocytes were HHV-6 DNA positive. He engrafted on day 18 but the ANC dropped from 5.5 x 10(9)/l (day 23) to 0.48 x 10(9)/l (day 34) with persistent HHV-6 DNAemia. Bone marrow on day 35 was positive for HHV-6 DNA. He was treated with G-CSF and ganciclovir with good response. He later had pneumonitis which was treated empirically with foscarnet, ceftazidime and clarithromycin.     

Mechanical environment associated with rotator cuff tears

The patient is a 12-year-old boy with acute mixed lineage leukemia (AMLL) and with a rare karyotype of trisomy 6. He was referred to our hospital with gingival swelling, bleeding at the conjunctiva and huge hepatosplenomegaly. Complete blood count revealed leukocytosis with 79% blasts, anemia and thrombocytopenia. Bone marrow examination revealed 82.5% blasts which were morphologically judged as M1 according to the French-American-British classification. Immunophenotyping of leukemic cells showed the presence of CD2, CD7, CD19 and CD13 antigens, suggesting the diagnosis of AMLL. Cytogenetic analysis revealed a single abnormal karyotype of 47,XY,+6,add(15)(q22) which was successfully detected by fluorescence in situ hybridization (FISH) with the probe mapping at the alpha-satellite region of chromosome 6. Although the patient was treated with several chemotherapy regimens, he could not achieve complete remission and he died of progressive disease 11 months after admission. Fluorescence in situ hybridization analysis was very informative in assessing the residual leukemic cells in interphase during his clinical course.     

Antiphospholipid antibodies syndrome

OBJECTIVE: To measure the prognostic utility of helper T-cell (CD4) counts in human immunodeficiency virus (HIV)-infected patients undergoing major abdominal surgery. DESIGN: Retrospective case series. SETTING: Three university-affiliated hospitals. PATIENTS: Forty-three HIV-infected patients undergoing major abdominal surgery. MAIN OUTCOME MEASURES: Morbidity and mortality rates with respect to CD4 cell counts. RESULTS: Nineteen of 32 patients who had CD4 cell counts less than 0.20 X 10(9)/L (200 cells/microL) suffered major complications compared with 2 of 11 patients who had CD4 cell counts greater than 0.20 x 10(9)/L (200 cells/microL) (P=.03). Perioperative mortality was 38% for patients with CD4 cell counts less than 0.20 x 10(9)/L, and was 9% for those with CD4 cell counts greater than 0.20 x 10(9)/L (P=.13). Six months postoperatively, mortality rates were 47% and 9%, respectively (P=.03). Of patients with septic processes perioperatively (n=12), mortality was 75%, and was 19% (P=.009) for those with nonseptic processes (n=31). Nine patients had HIV-related intra-abdominal pathologic conditions at laparotomy. Mortality was 56% perioperatively (P=.13) and 88% after 6 months (P=.001). Sixty-eight percent of patients who received blood product transfusions developed complications, whereas only 7% of those who did not receive transfusions developed complications (P<.001). Overall mortality and morbidity rates were 37% and 49%, respectively. Patients with morbidity had lower CD4 cell counts (median, 0.034 x 10(9)/L) than those without complications (median, 0.102 x 10(9)/L) (P=.02). Similarly, patients who died had lower CD4 cell counts (median, 0.031 x 10(9)/L vs 0.088 x 10(9)/L) (P=.05). CONCLUSIONS: Patients with acquired immunodeficiency syndrome-defining CD4 cell counts undergoing major abdominal surgery developed more complications and had poorer outcomes at 6-month follow-up compared with HIV-infected patients whose CD4 cell counts were greater than 0.20 x 10(9)/L (200 cells/microL). A perioperative septic process and HIV-related pathologic conditions seen at laparotomy are also associated with worse outcomes.