Biomedical subjects

F Keil

Publications and source records attributed to F Keil.

At least 19 recordsLinked to original sources

PubMed1998

Subdural hygromas after bone marrow transplantation: results of a prospective study.

BACKGROUND: Subdural hygromas after bone marrow transplantation (BMT) have been occasionally found in patients with persisting headache and vomiting. We assessed the incidence of subdural hygromas after BMT and tried to define possible risk factors associated with this complication. METHODS: Fifty bone marrow graft recipients surviving more than 30 days were consecutively enrolled into a prospective study. Cranial CT scans were performed before and 30 days after BMT. Clinical data and symptoms were recorded daily during the first 30 days after BMT. In patients with subdural hygromas, a magnetic resonance imaging scan and monthly follow-up cranial computed tomography scans were performed until fluid collections had resolved completely. RESULTS: In 9 of the 50 patients (18%) who survived 30 days after transplantation, newly acquired subdural hygromas were found. Patients with hygromas suffered significantly longer and more severely from headache and vomiting (P=0.01). Application of intrathecal methotrexate and arterial hypertension occurred significantly more often in patients with hygromas (P=0.01). In a stepwise logistic regression model, arterial hypertension and intrathecal methotrexate application were the only independent risk factors for the development of hygromas. Monthly follow-up cranial computed tomography scans showed that all hygromas resolved completely after a median of 60 days after diagnosis (range: 30-120 days). CONCLUSIONS: Subdural hygromas are a frequent complication after BMT within the first 30 days after transplantation. They are reversible and disappear within 2-3 months. The need for routine application of intrathecal methotrexate in standard risk leukemia patients should be critically addressed. Furthermore, close monitoring of blood pressure and immediate antihypertensive therapy might contribute to avoid formation of subdural hygromas.

Adolescent↗

PubMed1998

Graft-versus-host disease following second syngeneic stem cell transplantation for relapsed chronic myeloid leukemia.

Allogeneic bone marrow transplantation is the only curative treatment for patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML); however, recurrence of disease remains a major cause of treatment failure. A 26-year-old man with chronic myeloid leukemia who had a cytogenetic relapse 49 months after his first syngeneic bone marrow transplant (BMT) and hematologic relapse 23 months thereafter progressed to blast crisis despite treatment with IFN-alpha for 15 months. He underwent a second transplantation in early second blast crisis, 92 months after the first BMT with PBPC from his previous donor. Successful hematological reconstitution occurred. On day 50 after the second transplantation the patient developed a generalized rash, hepatomegaly, and cholestatic signs. Skin and liver biopsy revealed changes compatible with acute graft-versus-host disease (GVHD). Treatment with cyclosporin A (CSA) and prednisone was started, and the GVHD resolved. Fifteen months after PBPC transplantation he had a molecular relapse. Despite discontinuation of CSA, the patient progressed into blast crisis 7 months later. The occurrence of GVHD and disappearance of the BCR-ABL-positive clone suggest that a graft-versus-leukemia (GVL) effect may have been operative for 15 months in a patient given a second syngeneic BMT in blast crisis.

Adult↗

PubMed1998

Leukemia-free survival and mortality in patients with refractory or relapsed acute leukemia given marrow transplants from sibling and unrelated donors.

Between April 1982 and February 1997 39 patients (24 male, 15 female) with refractory acute leukemia and a median age of 31 years (19-51 years) received allogeneic marrow grafts from an HLA-identical sibling (n = 27), HLA-identical unrelated donor (MUD; n = 10) or 1-antigen mismatched unrelated donor (n = 2). Twenty-eight patients had acute myelogenous leukemia and 11 acute lymphoblastic leukemia. For conditioning most patients received total body irradiation combined with cyclophosphamide (n = 23) or etoposide (n = 7). For graft-versus-host disease prophylaxis patients received cyclosporin A (CsA) and methotrexate (MTX) (n = 20), MTX alone (n = 3), CsA and methylprednisone (n = 6), or CsA alone (n = 10), respectively. As of June 1997 probability of leukemia-free survival projected to 3 years after BMT was 14% for patients given sibling marrow grafts and 28% after MUD transplantation. Transplant-related mortality projected to 3 years was 32% after sibling and 37% after MUD marrow grafting. Although not significantly different, probability of relapse projected to 3 years after BMT was lower after MUD at 56% compared to 78% with sibling BMT. Thus, high-dose chemo/radiotherapy followed by allogeneic marrow infusion has a curative potential for patients with refractory leukemia and offers the chance of long-term disease-free survival for some patients.

Acute Disease↗

PubMed1998

Successful management of adult respiratory distress syndrome (ARDS) after high-dose chemotherapy and peripheral blood progenitor cell rescue by non-invasive ventilatory support.

A 34-year-old man suffering from Hodgkin's disease underwent high-dose chemotherapy (CBV) followed by transplantation of autologous peripheral blood stem cells. On day +6 after peripheral blood stem cell transplant (PBSCT) bacterial pneumonia developed. Along with rapid engraftment during stimulation with G-CSF adult respiratory distress syndrome (ARDS) developed within 4 days. High-flow CPAP (continuous positive airway pressure) ventilation via a sealed face-mask was initiated. The patient tolerated the sealed face-mask very well, and CPAP was continuously administered for 4 days, thus avoiding intubation. High-flow CPAP may offer a therapeutic alternative in selected patients with respiratory compromise after PBSCT.

Adult↗

PubMed1998

Routine fluoroscopic guidance is not required for placement of Hickman catheters via the supraclavicular route.

The purpose of this study was to evaluate the efficacy and safety in placement of Hickman catheters via the supraclavicular route without fluoroscopic guidance. We studied 81 consecutive percutaneous placements of dual lumen Hickman catheters via the supraclavicular route without the use of fluoroscopic guidance. Success rates, technical problems, complications, infections and reasons for explantation were recorded prospectively. Seventy-nine punctures were successful (97.5%). One pneumothorax (1.2%) and three accidental arterial punctures (3.7%) occurred. Difficulties in introducing the catheter through the peel away sheath or misplacement were not observed. The catheters remained in place for a total of 7657 days (mean 94.5, range 3-392 days). Sixteen blood cultures were positive (2.1/1000 catheter days). Five catheters (6.1%) were lost because of mechanical complications. Forty-two lines (52%) were removed electively, 23 (28.4%) because of suspected infection, and two (2.5%) because of tunnel infection. Nine patients died with a functioning catheter. We conclude that the supraclavicular approach to the subclavian vein is safe and efficient for introduction of Hickman catheters. Using this access, routine fluoroscopic or sonographic guidance is not required for proper placement. Implantation of the lines in an intensive care unit did not lead to higher infection rates than those reported in the literature.

Arteries↗

PubMed1998

Bile duct adenocarcinoma mimicking veno-occlusive disease after autologous bone marrow transplantation for acute leukaemia.

A 52-year-old female underwent autologous BMT because of acute myeloid leukaemia FAB M4 in second remission. Since the patient had no HLA-identical sibling she received a purged autologous BM transplant. On day +5 she developed signs of a sepsis syndrome with fluid retention and was treated with broad-spectrum antibiotic therapy. However, her body weight remained high, ascites and an increase of total serum bilirubin and alkaline phosphatase developed. The icterus worsened to a total bilirubin level of 25 mg/100 ml. Sonographic and endoscopic imaging showed a dilated gall bladder but disclosed a post-hepatic cause for the icterus. A transjugular liver biopsy on day +71 revealed severe cholestasis and siderosis. The patient remained aplastic with constantly increased bilirubin levels. On day +73 septic shock syndrome occurred and the patient died of multiorgan failure 3 days later. At autopsy, a highly differentiated bile duct adenocarcinoma at the porta hepatis, so-called Klatskin tumour, was found, explaining the fatal course with intractable cholestasis.

Adenocarcinoma↗

PubMed1998

Competitive CBFbeta/MYH11 reverse-transcriptase polymerase chain reaction for quantitative assessment of minimal residual disease during postremission therapy in acute myeloid leukemia with inversion(16): a pilot study.

PURPOSE: (1) Quantification of minimal residual disease (MRD) by competitive CBFbeta/MYH11 reverse-transcriptase polymerase chain reaction (RT-PCR) in patients with acute myeloid leukemia (AML) and inversion(16) [inv(16)] during postremission therapy, (2) comparison of this method with conventional two-step RT-PCR, and (3) evaluation of a potential prognostic value. PATIENTS AND METHODS: MRD of six consecutive adult patients with AML and inv(16)(p13;q22) or t(16;16)(p13;q22) who entered complete remission (CR) was monitored by competitive CBFbeta/MYH11 RT-PCR in their bone marrow (BM) during postremission therapy with high-dose cytarabine (HiDAC) or after BM transplantation with a matched unrelated-donor marrow (MUD-BMT) during an observation period of 4.5 to 27 months after initiation of treatment. RESULTS: Competitive PCR showed a gradual decline by at least 4 orders of magnitude after 7 to 9 months in patients in continuous CR (CCR), while one patient who relapsed after 13.5 months only achieved a reduction by 2 orders of magnitude at the end of consolidation therapy. A rapid decrease below the detection limit was observed within 1 month in two patients after MUD-BMT. A temporary reappearance of molecular MRD was observed in these patients during immunosuppression for graft-versus-host disease (GvHD). After reduction of immunosuppression, the level of MRD dropped again below the PCR detection limit. Molecular monitoring by conventional two-step RT-PCR yielded comparable results only when multiple assays per time point were performed, while single-assay RT-PCR gave misleading results. CONCLUSION: Competitive RT-PCR is a valuable tool for molecular monitoring during postremission chemotherapy, as well as after BMT.

Adolescent↗

PubMed1998

Experience with allogeneic and syngeneic blood stem cell transplantation in patients with hematological malignancies.

Between 1995 and 1997 twenty two patients with different hematological diseases ( CML n=10, AML n=6, ALL n=l, NHL n=3, SAA n=1,solid tumor n=1 ) and a median age of 37 (range, 20 to 55) years received unmanipulated peripheral blood stem cell (PBSC) transplants from HLA-identical sibling donors at our institution. Myeloablative chemotherapy consisted of cyclophosphamide (CY) and total body irradiation in 11, and chemotherapy alone in 11 patients. For graft-versus host-disease (GVHD) prophylaxis all patients were given cyclosporine A and methotrexate according to the Seattle protocol. PBSC were mobilized by granulocyte colony-stimulating factor (G-CSF) given at 10 microg/kg body weight (b.w.)/day for four days. Harvest of PBSC was started on day 5 and continued on day 6 if necessary. A median of 1 leukapheresis (range, 1 to 2) was performed and a median of 5.7 x 10(6) CD34+cells/kg b.w. (1.34 to 21.5) were obtained. Ten patients received G-CSF (5 microg/kg b.w.) starting on day one after PBSCT until neutrophil recovery. Absolute neutrophil counts >0.5 x 10(9)/L and ANC >1.0 x 10(9)/L were reached after a median of 13 (range 8 to 18) and 15 (range 9 to 19) days after PBSCT. Unsupported platelet counts >20 x 10(9)/L and 50 x 10(9)/L were reached after 17 (range 8 to 32) and 22 (range 13 to 40) days after PBSCT, respectively. Incidence of acute GVHD grade I to IV was 52%, extensive chronic GVHD occurred in 25% of patients. After a median observation time of 11 (range, 3 to 34) months twelve patients (55%) are alive and well. In summary, infusion of allogeneic PBSC after myeloablative therapy allows rapid and sustained hematologic reconstitution. Incidence of acute GVHD is not increased, for assessment of chronic GVHD longer observation times and larger patient numbers are required.

Adult↗

PubMed1998

Matched unrelated donor marrow transplantation in patients with advanced acute leukemia.

Patients with advanced acute leukemia (AL) have a poor prognosis with death due to disease or complications of therapy. High-dose chemoradiotherapy followed by allogeneic marrow transplantation (BMT) has been used to overcome resistance of the leukemic clone resulting in long-term survival of up to 20%. Due to lack of suitable related donors BMT from an HLA-compatible unrelated donor (MUD) has been increasingly applied in these patients during the last years. Between January 1991 and August 1997 twenty five patients with advanced acute myeloid (n=19) or lymphoid (n=6) leukemia, 11 males and 14 females, age 22 to 41 (median 32) years received MUD (n=22) or 1-antigen mismatched unrelated donor (n=3) grafts. In four patients an autologous BMT had been performed previously. For conditioning all patients were given total body irradiation containing regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CSA) and methotrexate (n=24) or CSA and methylprednisone (n=1). In 23 patients (92%) class II region compatibility was assessed by DRB1, DRB3, DRB5, and DQB1 allele typing by hybridization of amplified DNA with ligation based typing. In 2 patients HLA-DR typing was performed by two colour fluorescence cytotoxicity test and mixed lymphocyte cultures. As of November 1997 10/25 patients (40%) are surviving leukemia-free after a median observation time of 17 (range, 3 to 38) months. Transplant-related mortality was an overall of 36% and 28% in patients receiving their first BMT. In 6/25 patients (24%) relapse occurred 2 to 26 months after BMT. Incidence of acute GVHD grade I to IV was 85%. The probability of relapse projected at 3 years was 35%. High-dose chemoradiotherapy followed by MUD marrow infusion has a curative potential for patients with advanced acute leukemia and offers the chance of long-term leukemia-free survival. Currently, up to 80% of patients with acute myelogenous leukemia (AML) and acute lymphoid leukemia (ALL) under the age of 50 years achieve complete hematological remission (CR) with conventional dose chemotherapy. However, in patients who are refractory to induction chemotherapy or relapse prognosis is still poor. There, high-dose chemoradiotherapy followed by allogeneic marrow infusion has been used to overcome resistance of the refractory leukemic clone and has resulted in long-term survival. For selected patients lacking a human leukocyte antigen (HLA) compatible family donor marrow transplantation (BMT) with a suitable unrelated marrow donor (MUD) has become a feasible and effective treatment. Here, we report our experience in patients with advanced acute leukemia given marrow grafts from unrelated donors.

Acute Disease↗

PubMed1998

Long term follow up after allogeneic stem cell transplantation for chronic myelogenous leukemia.

Between January 1983 and July 1997, 83 patients (35 female, 48 male) with a median age of 37 (19-57) years with chronic myelogenous leukemia (CML) were admitted for bone marrow transplantation (BMT) at the University hospital of Vienna. Fifty-six patients were in chronic phase, 17 in accelerated and 10 had blast crisis. Marrow donors were: HLA-identical siblings in 62 patients, 2-antigen mismatched related donor in 2, HLA-identical unrelated donors (MUD) in 17 and 1-antigen mismatched unrelated donor in 2 patients. The median time from diagnosis to BMT was 22 (2-91) months. Conditioning therapy consisted of cyclophosphamide (CY) and total body irradiation or CY and busulfan. For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) alone, MTX and cyclosporine A (CSA), CSA alone or CSA and methylprednisone were given. Durable engraftment was documented in 75 of 77 patients (97%). As of July 31, 1997 48 patients are alive (58%), 36 (56%) after sibling transplantation with a median observation time of 77 months and 12 (63%) after MUD transplantation with a median observation time of 13 months. Overall survival for patients in chronic phase (CP) at time of BMT is 64%, 53% for patients in acceleration and 30% for patients in blast crisis (BC). Disease-free survival (DFS) after sibling BMT and unrelated donor transplantation is 53% and 58%, respectively. Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 33% after sibling and 32% after MUD transplantation. Thus, sibling and unrelated donor BMT offer high cure rates with acceptable toxicity to patients with CML.

Adult↗

PubMed1997

Donor leukocyte infusion for leukemic relapse after allogeneic marrow transplantation: lack of residual donor hematopoiesis predicts aplasia.

We assessed the chimerism of CD34+ bone marrow cells before donor leukocyte infusion (DLI) on nine occasions in seven patients with leukemic relapse after allogeneic marrow transplantation. The patients suffered from acute lymphoblastic leukemia (n = 1), acute myeloid leukemia (n = 3), and chronic myeloid leukemia (CML; n = 3). Two patients received a second DLI because of disease progression after the first one. The origin of the CD34+ cells was determined by analyzing variable number of tandem repeats with polymerase chain reaction and, in sex-mismatched cases, by fluorescence in situ hybridization. Before DLI CD34+ cells were exclusively of donor origin in four patients. In another patient 41% of CD34+ cells were derived from the donor. No aplasia occurred in these patients after DLI, whereas in the two patients with exclusively recipient hematopoiesis severe aplasia lasting for 5 and 13 weeks necessitated hematopoietic stem cell support. One patient who had only 5% CD34+ donor cells before DLI recovered without stem cell support after 10 days. Two patients in relapse of CML showed a high percentage of BCR-ABL- CD34+ cells of recipient origin before DLI. These BCR-ABL- cells of recipient type did not prevent severe aplasia which indicates that the assessment of BCR-ABL+ hematopoiesis alone is insufficient for predicting aplasia. Our data indicate that in case of sufficient donor hematopoiesis before DLI no persistent aplasia will occur. Thus, evaluation of donor hematopoiesis allows prediction of aplasia after DLI and makes early therapeutic interventions possible.

Acute Disease↗

PubMed1997

Cyclosporin A-induced ocular flutter after marrow transplantation.

Ocular flutter is a rare neurologic condition occurring in patients suffering from viral encephalitis, intracranial neoplasia, paraneoplastic syndrome or intoxications. Neurotoxicity is a recognized complication of cyclosporin A (CsA) therapy, but ocular flutter has not been reported in association with CsA administration to date. We describe a 17-year-old female patient who developed ocular flutter 51 days after transplantation with marrow from an unrelated donor, for acute myeloid leukemia. After discontinuation of cyclosporin, which was given for prophylaxis of graft-versus-host disease, the clinical symptoms resolved within 3 weeks, but a slightly abnormal electrooculogram persisted for more than 10 months.

Acute Disease↗

PubMed1997

Excellent long-term survival after allogeneic marrow transplantation in patients with severe aplastic anemia.

Between 1982 and 1996, 20 patients (10 male, 10 female) with severe aplastic anemia (SAA) with a median age of 25 years (17-37 years), received grafts from an HLA-identical sibling (n = 17), HLA-identical unrelated donor (n = 2) or identical twin (n = 1). The median time from diagnosis to marrow transplantation (BMT) was 15 months (range 1-96 months). More than half of the patients had received more than 10 units of red blood cells or platelet transfusions prior to BMT. Pretransplant immunosuppression consisted of cyclophosphamide (CY) alone (n = 10), CY in combination with total body irradiation (n = 8), and CY and antithymocyte globulin (n = 2). For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) alone (n = 9) or MTX with cyclosporin A (n = 10) were given. One patient died on day 18 after marrow grafting due to infection; all other patients had complete and sustained engraftment (95%). Eight patients developed acute GVHD (42%), nine patients chronic GVHD (53%) including four with extensive disease manifestation. One patient experienced a secondary malignancy 11 years after BMT. Eighteen patients followed for a median of 9.45 years (0.42-14.7 years) have sustained hematological reconstitution and are alive and well with a Karnofsky performance score of at least 90%. Thus, excellent long-term survival and low morbidity make allogeneic or syngeneic BMT the treatment of choice for younger patients with severe aplastic anemia.

Adolescent↗

PubMed1997

Relapse of Philadelphia chromosome positive acute lymphoblastic leukaemia after marrow transplantation: sustained molecular remission after early and dose-escalating infusion of donor leucocytes.

We present a patient who underwent sibling allogeneic BMT because of refractory Ph+ve ALL and remained BCR-ABL-positive after marrow grafting. Haemopoietic precursor cells were predominantly BCR-ABL-negative and of donor origin. In T cells an exclusively donor genotype was demonstrated. Despite donor leucocyte infusion (DLI), 20 weeks after BMT BCR-ABL fusion mRNA increased in semiquantitative polymerase chain reaction and leukaemic infiltration of the patient's bone marrow was seen. After a second course of DLI the patient achieved sustained molecular remission but he developed severe graft-versus-host disease (GvHD) and died from bacterial sepsis 9 months after DLI.

Adult↗

PubMed1996

Long-term leukemia-free survival after allogeneic marrow transplantation in patients with acute myelogenous leukemia.

Between February 1982 and April 1995, 62 patients (37 male, 25 female) with acute myelogenous leukemia (AML) with a median age of 32 years (19-51 years) received allogeneic marrow grafts from an HLA-identical sibling (n=60) or an HLA-mismatched family member (n=2). At the time of transplant, 35 patients were in first complete remission (CR), five in second CR, eight were primary refractory, eight were in untreated relapse and six in refractory relapse. The FAB subtypes were as follows: M1 (n=17), M2 (n=13), M3 (n=6), M4 (n=19), M5 (n=6), M6 (n=1). For conditioning most patients were given total body irradiation combined with cyclophosphamide (CY, n=50) or CY and busulfan (n=9). For graft-versus-host disease prophylaxis patients received cyclosporin A (CSA) and methotrexate (MTX) (n=32), MTX alone (n=12), CSA and methylprednisone (n=5), or CSA alone (n=13). As of April 1995, probability of leukemia-free survival projected at 10 years after BMT was 60% for patients transplanted in first CR compared with 10% for patients transplanted beyond first CR. Transplant-related mortality was 11% after BMT in first CR and 39% after BMT beyond first CR. Probability of relapse projected at 10 years after BMT is 32% for patients who received transplants in first CR and 81% for patients who received transplants beyond first CR. Thus, high-dose chemo/radiotherapy followed by allogeneic marrow infusion has a high curative potential for patients with AML who receive transplants in first CR and offers the chance of long-term disease-free survival for some patients with advanced disease.

Acute Disease↗

PubMed1996

Graft failure after donor leucocyte infusion in relapsed chronic myeloid leukaemia: successful treatment with cyclophosphamide and antithymocyte globulin followed by peripheral blood stem cell infusion.

We report a patient with chronic myeloid leukaemia who underwent allogeneic marrow transplantation (BMT) but had a molecular relapse 5 months and haematological relapse 15 months after BMT. Since therapy with alpha-interferon had been ineffective he received leucocyte infusions from his sibling donor. He developed acute graft-versus-host disease and became aplastic 6 weeks later. Despite donor marrow infusion and cytokine stimulation marrow aplasia persisted for 13 weeks. Then, donors' peripheral blood stem cells were given after conditioning with cyclophosphamide and antithymocyte globulin resulting in trilineage engraftment of donor haemopoiesis. Since then, the patient has been in continuous molecular remission for 11 months.

Antilymphocyte Serum↗

PubMed1996

G-CSF stimulation of donor myelopoiesis prolongs survival of relapsed BCR-ABL-positive acute lymphoblastic leukemia after allogeneic marrow transplantation.

An allogeneic sex-mismatched BMT which was performed in a male patient with BCR-ABL-positive ALL in second hematological and central nervous system relapse resulted in a CR for 12 months. After BMT, the patient was closely monitored with reverse transcription (RT)-PCR. One month before a third relapse RT-PCR became positive. During relapse G-CSF was administered. It specifically stimulated the donor-derived myelopoiesis and led to the stabilization of the disease for 8 months. Fluorescence in situ hybridization analyses of individual cell populations revealed that during the whole course of G-CSF administration granulocytes, CD4+, CD8+ and CD34+/CD10- cells were of female (donor) origin and only the CD34+/CD10+ cells which represented the leukemic blasts, were of male (host) origin.

Adult↗

PubMed1996

[Results of critical care management of patients after bone marrow transplantation].

In a retrospective study we investigated the clinical course of patients who required intensive care support after bone marrow transplantation. Out of 25 patients only 5 (20%) survived treatment in the intensive care unit (ICU) and this group showed a significantly lower age, lower APACHE III and organ-failure scores and higher serum albumin values, as well as a longer interval between bone marrow transplantation and admission to intensive care. However, no patient requiring mechanical ventilation primarily for pneumonia or other infections arising as a complication of bone marrow transplantation survived intensive care. All patients requiring ventilation for more than 24 hours died in hospital. Of the 5 patients surviving ICU treatment only 3 were eventually discharged from hospital and only one single patient was alive after 6 months. Hence, current intensive care management appears to be indicated in only a small group of patients after bone marrow transplantation.

APACHE↗