[Initial experiences with pentamidine aerosol in prevention of Pneumocystis carinii pneumonia following bone marrow transplantation]. / Erste Erfahrungen mit Pentamidin-Aerosol zur Prophylaxe der Pneumocystis-carinii-Pneumonie nach Knochenmarktransplantation.

After bone marrow transplantation there is a risk of 10% to acquire a pneumonia caused by pneumocystis carinii, if no prophylaxis is used. So far cotrimoxazol is the treatment of choice from day -14 before to day +180 after bone marrow transplantation. This substance, however, may cause allergic reactions, may augment the risk of nephrotoxicity of other drugs, and may be myelosuppressive. The prophylaxis with pentamidine-inhalation was used in 26 patients after bone marrow transplantation so far. It could be shown, that after salbutamol-inhalation 60 to 300 mg of pentamidine can be given safely in 14 to 28 days intervals. The main side effects were cough and dyspnea in some patients. Only minimal amounts of the drug could be detected in serum and urine after application. No toxic side effects and no pneumocystis carinii pneumonia were observed.

[Isolated infiltration of the vitreous body as a sign of blast crisis in chronic myeloid leukemia]. / Isolierte Glaskörperinfiltration als Zeichen einer Blastenkrise bei chronisch myeloischer Leukämie.

A 29-year-old man with chronic myeloid leukemia and two successfully treated blast crises exhibited ocular symptoms. Eighteen months after the diagnosis of leukemia he presented with unilateral hyperplastic iris stroma, anterior chamber inflammation and vitreous infiltration. Uveitis was diagnosed tentatively, and local therapy was begun with corticosteroids. Because the findings remained unchanged an invasive diagnostic evaluation followed. Although iris biopsy revealed only unspecific mononuclear cell infiltration (mainly T-lymphocytes), selectively aspirated vitreous material contained myeloid cells of different stages of maturation and blast cells. Peripheral blood, liquor and bone marrow showed no signs of acceleration or transition of the primary disease. Thus, an extramedullary blast crises with isolated vitreous infiltration was diagnosed.

[Transplantation of bone marrow from unrelated donors in chronic myeloid leukemia]. / Transplantation von Knochenmark unverwandter Spender bei chronischer myeloischer Leukämie.

Bone marrow transplantations in four patients (aged 8-28 years, median 27 years) with chronic myeloid leukaemia (CML) were performed from unrelated donors who were HLA-identical and MLC-negative. One patient was in the stage of refractory blast crisis, one in a chronic phase, and two in the second chronic phase. Conditioning treatment consisted of fractionated radiation and administration of cyclophosphamide; in the patients with their second chronic phase additionally etoposide. Cyclosporin A and methotrexate were administered to prevent graft versus host reaction. The patient in the blast crisis died on day 12 after transplantation of Candida pneumonia. The other three patients are still alive 128, 306 and 530 days, respectively, after transplantation, only a mild form of graft versus host disease having occurred. It is suggested that for patients younger then 50 years with CML in the chronic phase an unrelated donor should be searched for in the absence of a familial donor.

Significant reduction of cytomegalovirus (CMV) disease by prophylaxis with CMV hyperimmune globulin plus oral acyclovir.

The effect of prophylactic intravenous administration of a cytomegalovirus (CMV) hyperimmune globulin with a high titer of neutralizing antibodies plus oral acyclovir was studied in 93 consecutive bone marrow transplant recipients. In spite of receiving blood products unscreened for CMV only six patients developed CMV infections during the time they received passive immunization. Five patients reactivated virus after hyperimmune globulin infusions were stopped; four of them suffered from chronic graft-versus-host disease (GVHD) Among the patients suffering from acute GVHD grade III/IV and/or chronic GVHD the incidence of CMV infection (10/38) was significantly higher than among those with no or milder forms of GVHD (1/55) (p less than 0.01). Only three patients suffered from symptomatic CMV infections; two with gastrointestinal manifestations and one with fatal CMV pneumonia. Thus CMV prophylaxis as used here proved highly effective in combating one of the major difficulties encountered in BMT.

Correlation between low CSA plasma concentration and severity of acute GvHD in bone marrow transplantation.

Between 1982 and 1986 51 patients were treated with ciclosporin a (CSA) to prevent graft versus host disease (GvHD) after bone marrow transplantation (BMT). Major side effects of the drug were tremor, hypertension, hepatotoxicity and nephrotoxicity. Acute GvHD 0 degree to II degree occurred in 80% of our patients, and GvHD III degree and IV degree in 20% despite the use of CSA. Two to four days before the onset of GvHD, CSA serum levels were significantly lower on the average in patients who developed GvHD III degree and IV degree compared to the others. Our data indicate that plasma CSA concentrations higher than 250 ng/ml should be achieved to reduce the severity of GvHD after BMT.

Prevention of CMV infection after BMT in high-risk patients using CMV hyperimmune globulin.

Prophylactic administration of an intravenous cytomegalovirus hyperimmune globulin in bone marrow transplant recipients provided protection against primary as well as reactivated CMV infection in patients considered to be at high risk for cytomegalovirus infections. Forty-one patients were divided in six subgroups according to factors considered to increase the incidence and severity of CMV infections following bone marrow transplantation. All of these patients received blood products from donors not screened for active or latent CMV infections. In spite of this, patients undergoing intensified conditioning therapy or mismatch transplantation, as well as those transplanted in relapse of their leukemia and even patients receiving granulocyte transfusions from donors unscreened for CMV serostatus, were found not to develop primary or secondary CMV infections. Only in the group of patients older than 35 years and among those suffering from severe GVHD six patients were found to have CMV infections, only two a symptomatic form. Intravenous administration of CMV hyperimmune globulin effectively protected even patients at high risk for CMV infection against severe complications of primary infection or reactivation of this virus.

[Bone marrow transplantation in acute leukemia, chronic myeloid leukemia, severe aplastic anemia and stage IV neuroblastoma. Effect of antiviral prevention with anti-CMV-hyperimmunoglobulin and acyclovir]. / Knochenmarktransplantation bei akuter Leukämie, chronisch myeloischer Leukämie, schwerer aplastischer Anämie und Neuroblastom Stadium IV. Einfluss antiviraler Prophylaxe mit Anti-CMV-Hyperimmunglobulin und Azyklovir.

Bone marrow transplantation was performed between IV/82 and X/85 in 64 patients with acute leukemia (n = 36), chronic myelogenous leukemia (CML; n = 13), severe aplastic anemia (n = 12), and neuroblastoma stage IV (n = 3). Of these patients 57 received allogeneic marrow from HLA-ABCDR identical, MLC-negative sibling donors. Six transplants were performed with syngenic marrow and one with autologous marrow. Of the 64 patients 48 survived 40-1,250 days after transplantation, resulting in a survival rate (SR) of 75% and a survival probability (SP) of 71%. Of the 36 patients suffering from acute leukemia (SR = 64%, SP = 51%), patients with acute myelogenous leukemia (AML) in first complete remission (n = 11; SR = 81%, SP = 76%), as well as patients with acute lymphatic leukemia (ALL) in 1st to 4th complete remission at the time of transplantation (n = 14; SR = 81%, SP = 76%) show a favorable prognosis. A poor survival rate was seen for patients with AML when transplanted in second or partial remission (1/5; SR = 20%), as well as for patients suffering from ALL and transplanted during relapse or partial remission (1/6; SR = 16%). Of 13 patients suffering from CML 12 survived the transplantation free of relapse (SR = 93%, SP = 92%), and one patient died from varicella zoster pneumonia. Of the transplanted patients with severe aplastic anemia, 12 of 13 are surviving with complete hematologic reconstitution; one patient, however, died on day 10 from a sepsis. In our patient group, the SR as well as the SP has been improved through changes in the irradiation protocol concomitant with prophylactic application of anti-CMV hypergammaglobulin, as well as through additional oral medication of Azyklovir. The 41 patients (BMT No. 7-47) with total body irradiation at one time show an SR of 44% and an SP of 41%. The following 46 patients (BMT No. 48-93) have reached an SR of 83% and an SP of 74% under the regimen of fractionated total body irradiation, plus prophylaxis with anti-CMV hypergammaglobulin and Azyklovir. Within this group, no fatal CMV pneumonia was encountered as opposed to six patients lost from CMV pneumonia in the first group.

[Bone marrow transplantation in severe aplastic anemia]. / Knochenmarktransplantation bei schwerer aplastischer Anämie.

Bone marrow transplantations were performed on 15 patients (aged 5-39 years) with severe aplastic anaemia. Twelve patients are alive 76-1930 days (median 668 d) after transplantation, with complete haematopoetic recovery. Total-body radiation with 3.6 Gy in four patients, cyclosporin A administration to ten patients and buffy-coat transfusion to nine patients entirely prevented early rejection. Two patients died of pneumonia (aspergillus; varicella-zoster virus), one patient died of bleeding from a splenic-artery aneurysm. In patients under the age of 40 years with severe aplastic anaemia bone marrow transplantation as early as possible after diagnosis is the treatment of choice if HLA-identical siblings are available as donors. In patients over 40 years treatment should at first be tried with antithymocyte globulin.

[Bone marrow transplantation in chronic myeloid leukemia. Influence of gnotobiotic measures, especially antiviral prophylaxis]. / Knochenmarktransplantation bei chronischer myeloischer Leukämie. Einfluss gnotobiotischer Massnahmen, insbesondere antiviraler Prophylaxe.

Bone marrow from HLA-identical siblings was transplanted in 14 patients with chronic myeloid leukaemia (CML), including one patient in acceleration phase and one in chronic phase following 2 blast crises. Restoration of the bone-marrow occurred in all cases and Philadelphia chromosome could not be detected in any of the patients after the transplantation. Two patients died due to lung complications. Twelve patients who received antiviral prophylaxis (aciclovir per os, anti-CMV-hyperimmunoglobulin) after the transplantation are in very good condition with 140 to 790 days complete clinical and cytogenetic remission. Bone-marrow transplantation, as a curative measure for patients with CML up to the age of 45 (50), should be included in therapy schemes when an HLA-identical sibling is available.

Creatinine clearance and renal interstitium in diffuse endocapillary proliferative glomerulonephritis.

Morphometric investigations of the renal cortex on biopsies obtained from patients with diffuse proliferative endocapillary glomerulonephritis (EPGN) were compared to biopsies without pathological changes, both groups having a normal serum creatinine concentration at the time of biopsy. Our findings are as follows: In both groups a statistically significant correlation exists between the decrease of the endogenous creatinine clearance and the broadening of the interstitium. The mean endogenous creatinine clearance value in EPGN is 107.6 +/- 40.6 ml/min/1.73 qm, the mean endogenous creatinine clearance in normal kidneys is 108.2 +/- 28.5 ml/min/1.73 qm; the mean interstitial volume in EPGN is 14.5 +/- 2.9 vol.%, that in normal kidneys 9.5 +/- 2.9 vol.%, the difference is statistically significant. Comparing the run of the two curves (relationship between endogenous creatinine clearance and interstitial volume) of the investigated groups, one finds that they run a nearly parallel course, the curve of the EPGN being shifted statistically significant to the right. The mean values of number, single- and total area of the peri- and intertubular capillaries are identical in the cases of EPGN and in those biopsies without pathological findings. Furthermore no correlations could be established between the above mentioned measuring values and the endogenous creatinine clearance in the both investigated groups. Consequently in these cases with normal serum creatinine concentration the reduction of the glomerular filtration rate (gfr) accompanied by interstitial broadening cannot be explained by an impairment of the postglomerular blood flow. Perhaps a tubular functional disturbance, the cause or the consequence of the interstitial broadening impairs glomerular function by the tubular-glomerular feedback-mechanism and/or by an elevation of the intratubular hydrostatic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Collection and cryopreservation of mononuclear blood leukocytes and of CFU-C in man.

For bone marrow reconstitution after hemopoietic failure as a consequence of the action of a variety of etiological factors, hemopoietic stem cells are needed. These have been derived in the past mainly from bone marrow. This report describes studies and their results that indicate that granulocytic progenitor cells, measured in cell culture systems as "colony forming units in culture - CFU-C", can be collected in large quantities from the peripheral blood of human blood donors by continuous flow leukapheresis. They can be stored at ultra-low temperatures. Their recovery rate after thawing and washing is better than 85%. In a canine model, evidence was obtained that the presence of CFU-C in a suspension of mononuclear blood leukocytes is also indicative for the presence of pluripotent hemopoietic stem-cells. Therefore it is suggested that stem cells can also be collected from human blood as an alternative source for bone marrow reconstitution.