B. Hertenstein

Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia

SummaryThe incidence of invasive fungal infections after bone marrow transplantation (BMT) was analyzed in 303 consecutive marrow graft recipients (allogeneicn=271, autologousn=27, syngeneicn=5). All patients received inhalations with amphotericin B (10 mg twice daily) during neutropenia. The overall incidence of invasive fungal infections within the first 120 days after transplant was 3.6% (11/303; aspergillosis: 6; yeast infection: 5). Four of the 11 cases occurred early, and seven cases were observed after neutrophil recovery and discontinuation of amphotericin B inhalation treatment. Late infection was significantly associated with the development of acute graft-versus-host disease. Four of the 11 infections (early 2/4; late: 2/7) were observed in patients with a history of previous fungal infection. Other patient and treatment characteristics were not helpful in defining potential risk factors. In particular, the incidence of invasive fungal infections did not differ between patients with more or less strict reverse isolation measures. Occasional side effects such as initial mild cough and bad taste were rare, usually disappeared during continued administration, and were in no case the reason for discontinuation of treatment. These data suggest that aerosolized amphotericin B may be a useful, convenient, and efficient prophylactic antifungal regimen in BMT.

Parvovirus B19 infection and bone marrow transplantation

SummaryParvovirus B19 lytically infects erythroid progenitor cells and thereby causes cessation of erythropoiesis in infected individuals. Anemia develops only if red cell turnover is increased, as in patients with chronic hemolysis (transient aplastic crisis). In addition to transient marrow failure, B19 can cause chronic anemia and, rarely, pancytopenia in immunodeficient patients who are not able to mount an adequate immune response to clear the virus. Bone marrow transplantation, although causing significant immunosuppression, is rarely complicated by symptomatic B19 infection. This is probably due to effective passive immunotherapy by immunoglobulin infusions immediately after transplantation and early reconstitution of antibody responses after uncomplicated transplantation.

Thrombotic thrombocytopenic purpura in early pregnancy with maternal and fetal survival

SummaryThrombotic thrombocytopenic purpura (TTP) is a hematologic disorder which is clinically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurologic symptoms, and cardiac and renal involvement. The pathogenic mechanisms of this disease are poorly understood. It is well known that TTP is associated with pregnancy and that prognosis for the mother and child is poor. We present the first case of a severe TTP diagnosed in the first trimester of pregnancy (13th week of gestation) with maternal survival and birth of a healthy child which required continuous and intensive treatment with plasmatherapy until delivery. During a period of 24 weeks several attempts to discontinue plasma therapy failed because of continuous active disease, and it became evident that plasma infusions were not as effective as plasma exchanges. The fact that the patient entered into remission soon after delivery of a healthy child by cesarean section in the 37th gestational week shows that in this case pregnancy activated an unknown factor which does not cross the placenta and which can be removed by plasmapheresis.

T-cell depletion versus methotrexate as GvHD-prophylaxis in allogeneic bone marrow transplantation for leukaemia

Graft‐versus‐host disease (GvHD) prophylaxis using methotrexate (23 patients) and T‐cell depletion of the graft (40 patients) was compared in 63 allogeneic bone marrow transplantations (BMT) for leukaemia. T‐cell depletion significantly reduced (p = 0.001) the incidence of GvHD from 68% to 11% and the GvHD‐associated mortality from 79% to 5%. Actuarial disease‐free survival for low‐risk patients (57% with T‐cell depletion and 47% with MTX) was not significantly improved, due to graft failure and possibly due to a higher leukaemic relapse rate after T‐cell depletion. Prevention of graft failure after T cell‐depleted BMT is essential and could also reduce the risk of leukaemic relapse by improved engraftment.

Pseudoreticulocytosis in a patient with myelodysplasia.

SummaryA patient with a myelodysplastic syndrome (MDS) and reticulocytosis of >50% in the absence of a correspondingly increased erythrocyte turnover is reported. Evaluation of the kinetics of erythrocyte turnover revealed a decreased erythrocyte life span of 44 days. From these data a prolongation of the reticulocyte maturation time to >20 days can be concluded. The patients erythrocytes lacked the increase of mean corpuscular volume and a significant increase of erythrocyte enzymes that would be expected in marked reticulocytosis. This finding suggests that the reticulocytes represented not newly formed red blood cells, but “pseudoreticulocytes”, i.e., mature erythrocytes that retained their substantia reticulofilamentosa.

Allogenic bone marrow transplantation of chemotherapy for patients with acute myeloid leukemia in first complete remission : a decision analysis approach

Abstract The methodology of decision analysis was originally developed to improve clinical decisions of physicians for individual patients. However, it is also well suited to support consensus procedures. We have used this methodology to analyse the question whether allogeneic bone marrow transplantation (BMT) or consolidation chemotherapy (CCT) should be used as first line postremission treatment in patients with acute myeloid leukemia. Main risk factors relevant for the outcome after BMT and CCT are therapy-related mortality and leukemic relapse, respectively. If the possibility of salvage BMT for patients relapsing after CCT is included, the outcomes of the two strategies come rather close. However, they are clearly different in subtypes of leukemia with high or low risk of relapse, and in patients at high risk for BMT-related mortality. Sensitivity analysis considering the variation of more than one risk factor provides valuable information for decision making for both individual patients and particular subgroups of patients with acute myeloid leukemia.

Emerging Bacterial Pathogens in Patients with Acute Leukemia: Viridans Streptococci and Non-Fermentative Gram-Negative Bacilli

Several recent reports indicate that the spectrum of bacterial pathogens causing major infections in patients with acute leukemia may have substantially changed over the past years. This report reviews the epidemiology and clinical significance of viridans group streptococci and non-fermentative gramnegative bacilli (other than Pseudomonas aeruginosa) causing bloodstream infections in acute leukemia patients at our center.

Allogeneic BMT in Patients with AML: Influence of the Prior Response to Induction Chemotherapy on Outcome After BMT

In chemotherapy treated patients the achievement of a complete remission is the prerequisite for cure. There is evidence that the kinetics of response is an important prognostic factor for the duration of remission. In patients undergoing allogeneic bone marrow transplantation supralethal radio/chemotherapy is given as conditioning regimen. Furthermore, an allogeneic graft versus leukaemia effect could be demonstrated. We analyzed whether primary responsiveness to chemotherapy influences the outcome after allogeneic bmt.

Fluoroquinolones for Infection Prevention After Bone Marrow Transplantation

The major morbidity of bone marrow transplantation remains infection and graft versus host disease (GVHD). Bacterial infections have been particularly common early after transplantation when profound neutropenia largely characterizes the immunodeficiency of the recipients. Previous attempts to reduce the incidence of bacterial infections during this period have included the use of protected environments and the administration of nonabsorbable agents for enteric decontamination. In a more recent study we found that norfloxacin may be as effective as neomycin/polymyxin or trimethoprimsulfamethoxazole/ polymyxin in gastrointestinal “decontamination” and infection prevention in bone marrow transplant patients [1]. Given the higher in vitro antibacterial activity and more favourable pharmacokinetic properties of ofloxacin compared with norfloxacin, we subsequently performed an open study of ofloxacin prophylaxis in adult bone marrow transplant recipients.

Allogeneic Bone Marrow Transplantation in Patients with Acute Leukemia with More Advanced Disease

After first relapse disease-free survival (DFS) is poor for patients with acute leukemia treated with chemotherapy alone. Chemotherapy studies revealed a long-term disease-free survival below 5% for patients with acute myeloid leukemia (AML) [1] and with acute lymphoblastic leukemia (ALL/AUL) (D. Hoelzer, personal communication). When a MHC (major histocompatibility complex) compatible bone marrow donor exists, the indication for bone marrow transplantation (BMT) is given. The following data represent the results of BMT in patients with acute leukemia beyond first remission transplanted between 1975 and 1990 at the University of Ulm.