[Bacillus subtilis infections].
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Abscess↗
Biomedical subjects
A Gratwohl
Publications and source records attributed to A Gratwohl.
[Late complications in patients with aplastic anemia].
Of 145 patients with severe aplastic anemia (SAA) treated in Basel from 1976 to 1987, 34 underwent bone marrow transplantation (BMT) and 111 received ALG therapy. We have analyzed the incidence of late complications in both groups of patients. 34 patients treated with ALG developed a hematological complication, 10 a myelodysplastic syndrome (MDS) and 18 paroxysmal nocturnal hemoglobinuria (PNH) associated with clinical symptoms in 12. Two patients had both MDS and PNH. Eight suffered relapse of SAA. After BMT neither of these complications occurred. Most of the non-hematological problems were associated with therapy. In the ALG group androgens were responsible for impotence and gynecomastia in men, deep voice in women and liver tumors in 4 patients. Four other patients developed aseptic necrosis of the hip and one carcinoma of the breast. The most severe late complication after BMT was chronic graft-versus-host disease (GvHD), occurring in patients still receiving methotrexate for prophylaxis of GvHD.
Anemia, Aplastic↗
Biological differences in the three major leukaemias.
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Bone Marrow Transplantation↗
[Ambulatory therapy with amphotericin B].
Therapy of systemic fungal infection with amphotericin B (AmB) must be continued for several months and is usually performed on an inpatient basis because of the risk of drug toxicity. Between 1983 and 1987 we treated 14 outpatients with a total of 164 AmB infusions. Side effects were generally mild and easy to control. Progressive impairment of renal function led to dose reduction and interruption of therapy in only one patient. Ambulatory therapy with AmB is feasible in an outpatient unit with adequate experience, and a significant reduction of treatment costs can result. Outpatient therapy is an acceptable alternative to inpatient treatment. Patients with malignant diseases under palliative therapy will profit most from the reduced duration of hospital stay.
Adolescent↗
Abundant macrophage growth in culture from patients with chronic myelogenous leukemia: a risk factor for graft-versus-host disease after bone marrow transplantation.
Peripheral blood cultures of hemopoietic precursor cells from 30 patients with chronic myelogenous leukemia showed different growth patterns before bone marrow transplantation. A strong increase of free and clustered macrophages was seen in 11/30. Of these 11 patients, 10 developed Graft-versus-Host Disease (GvHD). Of 19 patients without the macrophage pattern, 4 developed GvHD (p = 0.004). Of 14 patients with GvHD, 10 had shown the macrophage pattern before bone marrow transplantation, compared to 1/19 without GvHD (p = 0.004). We postulate that excess macrophages in the bone marrow recipient trigger GvHD by enhancing presentation of recipient antigens to donor T-lymphocytes, and that their presence is predictive of GvHD in CML.
Bone Marrow Transplantation↗
[A Candida krusei epidemic in a hematology department].
Candida krusei is a rarely isolated opportunistic yeast which we observed in 12 immunocompromised patients over a four-month period. Epidemiologic investigations identified the source of the organism in a bottle containing contaminated lemon juice in the hospital kitchen. Since elimination of the source we found the yeast in only 3 additional cases (4% vs. 0.4% of all patients with positive yeast cultures) over 11 months. Upper respiratory tract was the most common site of colonization. 6 of 15 patients developed infections with C. krusei (4 pneumonia, 1 disseminated infection and 1 localized). 4 died from fungal infections. - The importance of infection control institutions for efficient epidemiologic investigation of nosocomial infections is discussed.
Adult↗
Mutation analysis of the N-ras proto-oncogene in active and remission phase of human acute leukemias.
DNA isolated from blood or bone-marrow samples from 18 patients with acute non-lymphocytic leukemia (ANLL) and 14 patients with acute lymphocytic leukemia (ALL) was analyzed for the presence of mutations in the N-ras gene. Using synthetic oligonucleotide probes we detected mutations in 5 cases of ANLL; 4 GGT----GAT transitions in codon 12 and one CAA----AAA transversion in codon 61. One case exhibited homozygosity for the mutation. No mutations could be detected at these codons in the DNA of the 14 ALL patients. In a follow-up study with 3 of the above 5 patients, the mutation could no longer be detected in 2 cases following successful induction of clinical remission by chemotherapy. However, the mutated N-ras persisted in one patient who did not achieve remission. We show that oligonucleotide hybridization is a sensitive assay for the detection of N-ras point mutations, which in ANLL could be used to follow the fate of the leukemic clone during (and after) therapy.
Acute Disease↗
Hematological support in patients undergoing allogenetic bone marrow transplantation.
Bone marrow transplantation is impossible without effective support with blood components during the period of pancytopenia before graft function appears. We analyzed 39 patients with leukemia and three patients with severe aplastic anemia with regard to the pre- and postgrafting requirements for RBC and PLT transfusions. Overall a median of eight RBC and four PLT concentrates were necessary in all 42 patients after allogeneic BMT (ranges, 1-32 RBC and 1-11 PLT units). Requirements were identical irrespective of the underlying disease (ALL, AML, CML, SAA). Transfusion need for RBC and PLT concentrates increased in patients over 30 years old and with a major red blood group AB0 barrier between marrow donor and recipient. The presence of grade II-IV GvHD increased RBC requirements significantly, but not PLT requirements. In addition these patients were dependent on RBC transfusions for significantly longer periods. Only one patient required therapeutic granulocyte transfusions. In a CMV-negative patient with a CMV-negative marrow donor, who died of veno-occlusive disease, cytomegalovirus was transmitted inadvertently by a seropositive PLT concentrate in his final course. Our transfusion strategy included frozen deglycerolized RBC concentrates and single donor PLT concentrates, collected mainly from the marrow donor by a cell separator. All blood products were irradiated in vitro with 1500 cGy before transfusion. An optimal transfusion policy starting before BMT can contribute to successful bone marrow transplantation.
Adolescent↗
Secondary leukemia after severe aplastic anemia.
We describe a patient with acute myeloid leukemia (AML) occurring 5 years after successful treatment of severe aplastic anemia (SAA) with antilymphocyte globulin (ALG). Four years after ALG, SAA had relapsed. A second remission of SAA was achieved, but was followed by transformation of the myelodysplastic syndrome into overt AML. After 2 courses of high-dose cytosine arabinoside and VP-16 complete remission occurred. This case shows that chemotherapy of secondary leukemia after SAA is feasible, and that ex-aplastic bone marrow is capable of complete recovery from chemotherapy-induced aplasia. Morphological anomalies of bone marrow noticed early during remission of SAA might predict a late transformation in leukemia.
Adolescent↗
Bottled lemon juice--a cryptic source of invasive Candida infections in the immunocompromised host.
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Beverages↗
Late haematological complications in severe aplastic anaemia.
137 patients with severe aplastic anaemia (SAA) were treated in Basel from 1976 to 1986. 34 underwent bone marrow transplantation (BMT) and 103 received antilymphocyte globulin (ALG) therapy. We have analysed the incidence of late haematological complications in both groups of patients. 20 patients treated with ALG developed a late haematological complication. A myelodysplastic syndrome or frank leukaemia occurred in eight and paroxysmal nocturnal haemoglobinuria (PNH) in 13 patients. Nine of the 13 patients with PNH had clinical signs of haemolysis, four only had positive laboratory tests. One patient had PNH and acute leukaemia. The risk of developing a haematological complication increased continuously and reached 57% at 8 years. Neither PNH nor leukaemia occurred in patients treated with BMT. The increased survival rate and the long observation time after ALG therapy have revealed a new perspective of the prognosis of aplastic anaemia. Patients treated with BMT appear to be cured whereas those treated with ALG remain at risk for late complications.
Adolescent↗
Relapse after allogeneic bone marrow transplantation for acute leukaemia: a survey by the E.B.M.T. of 117 cases.
A multi-centre retrospective analysis on 117 patients relapsing after bone marrow transplantation (BMT) for acute leukaemia was carried out by the Leukaemia Working Party of the European Group for Bone Marrow Transplantation (E.B.M.T.). Forty-one patients had acute myeloid leukaemia (AML) and 76 had acute lymphoblastic leukaemia (ALL). Relapse occurred between 3 and 30 months after BMT and where investigated the leukaemia was found to have relapsed in recipient cells. In 10 cases the relapse was associated with new cytogenetic abnormalities. 74 patients received further treatment for leukaemia. Of these 21 out of 50 with ALL and 11 out of 24 with AML achieved a complete remission and had a median survival of 12 months compared with a median survival of 4 months for untreated patients or patients not achieving complete remission (P less than 0.001). Factors predictive for successful remission induction were a long interval between bone marrow transplant and relapse in ALL patients; and isolated extramedullary relapse. Presenting blast count, karyotype and remission status and number at the time of BMT were not predictive. Donor bone marrow was shown to be responsible for haemopoietic recovery occurring in the 21 out of 31 patients tested who achieved remission using donor karyotype or red blood cell antigens as markers. Nine patients received a second bone marrow transplant but only one became a long-term survivor. The results show that chemotherapy can usually prolong survival in selected patients with acute leukaemia relapsing after BMT but further BMT has a poor outlook.
Adolescent↗
Immunostimulatory effects of different antilymphocyte globulin preparations: a possible clue to their clinical effect.
Antilymphocyte globulin (ALG) and antithymocyte globulin (ATG) have an established role in the treatment of severe aplastic anaemia. The response rate ranges from 40% to 80%. Its mode of action is believed to be complement dependent lysis of immunocompetent cells which inhibit haemopoietic maturation. This might not be the sole mechanism. We have tested four different preparations of ALG/ATG for their mitogenic effect on normal peripheral blood cells and on enriched T-cells in vitro by 3H-thymidine incorporation. We found marked differences between the four preparations. One was strongly mitogenic and able to induce profound release of haemopoietic growth factors. This mitogenic effect could be detected in the serum of patients during ALG treatment. Clinical response rates of this preparation are about 80%. Three other preparations were of lower or no stimulatory effect. Clinical response rates with these preparations vary between 40% and 60%. From our results, we postulate that the beneficial effect of ALG could be partially due to its ability to stimulate release of haemopoietic growth factors. The mitogenicity of different ALG/ATG preparations should be tested as an in vitro parameter of clinical efficacy.
Adjuvants, Immunologic↗
Antilymphocyte globulin for myelodysplastic syndrome.
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Antilymphocyte Serum↗
Allogeneic bone marrow transplantation in leukemia.
This paper describes European experience of bone marrow transplantation for hematological malignancies. From 1979 until December 1986 2224 transplants were reported to the European registry. The results clearly show that the leukemia-free survival is highest when the transplant is performed in the first complete remission of acute leukemia or in the first chronic phase of chronic myeloid leukemia. Under these conditions 50% of the patients can be expected to be alive and well at 8 years after the transplantation. Other factors influencing leukemia-free survival are age, donor-recipient sex combination, and prevention of graft-versus-host disease with cyclosporine.
Adolescent↗
Irradiated donor buffy coat following T cell-depleted bone marrow transplants.
Twenty patients aged 27-47 years (median, 35 years) with hematological malignancies, treated with T cell-depleted bone marrow transplantation received in a pilot study five donations of 15 Gy irradiated donor buffy coat cells at days +1, +3, +5, +7, +14 in order to prevent rejection and leukemic relapse. Patients were conditioned with etoposide, cyclophosphamide and 12 Gy fractionated total body irradiation and given cyclosporine postgrafting. Donor bone marrow was T cell-depleted (median 3% remaining T cells) by counterflow elutriation. All patients engrafted. Fourteen (70%) are alive. Two are living with relapse, 12 (60%) are alive and well without any signs of disease, 2-27 months (median, 9 months) post-transplant. Three patients died of interstitial pneumonitis and/or graft-versus-host-disease; three died of relapse. This pilot study supports previous animal data. Repeated infusions of 15 Gy irradiated donor buffy coat are feasible and do not appear to increase transplant related mortality. Whether this approach ultimately will reduce the rate of rejection and relapse following T cell depletion needs to be confirmed in a larger, prospective study.
Adult↗
Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: report from the European Cooperative Group for bone marrow transplantation (8 cases).
Allogenic bone marrow transplantation (BMT) was performed in 8 patients with B chronic lymphocytic leukemia (CLL): 6 males and 2 females with a median age of 41 years (37 to 46). Seven patients were resistant to previous therapy and were grafted in the evolutive phase. Only 1 patient was grafted without any previous treatment. At the time of BMT 5 patients were classified according to the Rai classification in stage IV, 1 in stage III and 2 in stage 1. The delay between diagnosis and BMT was 47 months (5 to 68). Graft versus host disease (GVHD) prophylaxis was methotrexate (1 patient), cyclosporine (2 patients), methotrexate + cyclosporine (3 patients), cyclosporine + physical removal of T cells (2 patients). The conditioning regimen was standard for 5 patients, reinforced for 3 patients with Chlorambucil (1 patient) and etoposide (2 patients). A successful engraftment was obtained in all cases. The lymphocytosis decreased slowly and disappeared from day 0 to day 28. All patients developed an acute GVHD 5 of which resolved. Three patients died: 2 of acute GVHD and 1 of intracerebral hemorrhage. Five patients are alive in persistent complete remission without clinical symptoms and with normal peripheral blood and normal bone marrow. The median follow-up is 27 months (13-53). This small series suggests that allogeneic BMT should be investigated in selected patients as possible curative treatment of CLL.
Acute Disease↗
Failure of recombinant human granulocyte-macrophage colony-stimulating factor therapy in aplastic anemia patients with very severe neutropenia.
Four patients with very severe aplastic anemia refractory to antilymphocyte globulin were administered recombinant human granulocyte-macrophage--colony stimulating factor (GM-CSF). One patient with minimal residual myelopoiesis responded transiently to two separate courses of GM-CSF at 4 and 8 micrograms/kg/d administered intravenously and another course at 4 micrograms/kg/d administered subcutaneously. Septicemia and bilateral pneumonia that had been resistant to conventional therapy resolved. Three patients with no evidence of residual myelopoiesis did not respond to GM-CSF. In one patient, the dose was increased to 32 micrograms/kg/d with no effect on hematopoiesis. Immediate side effects were minimal at GM-CSF doses up to 16 micrograms/kg/d. GM-CSF may, however, have been involved in the pathophysiology of thrombosis of the inferior vena cava in the patient administered 32 micrograms/kg/d. We conclude that GM-CSF does not induce hematopoiesis in long-standing, severe, treatment-resistant aplastic anemia with complete myelopoietic failure. However, in patients with minimal residual myelopoiesis, GM-CSF could be a promising adjuvant therapy for severe infection.
Adult↗