ABSTRACT
In recent years, high dose chemotherapy followed by bone marrow rescue has been established as a common treatment of hematologic and solid tumor malignancies. Despite unequivocal success, relapse after transplant remains a serious problem, being the main cause of treatment failure. In an attempt to reduce relapse rates, we intensified the conditioning regimens consisting of busulfan/cyclophosphamide versus fractionated total body irradiation (f-TBI)/ cyclophosphamide by the addition of high dose etoposide. Toxicity profiles of 25 pediatric patients with hematologic malignancies undergoing intensified conditioning did not differ significantly between the two groups, except for a higher incidence of veno-occlusive disease in busulfan-treated patients (3 of 13 patients) compared with the TBI group (0 of 12 patients). We observed no transplant-related mortality in neither group. Regimen-associated morbidity was moderate and reversible in all cases. Five patients died in each treatment arm, due to relapse of the underlying disease. We conclude that both regimens are feasible in marrow transplantation of pediatric patients. Open randomized trials are needed to assess the efficacy of intensified conditioning in terms of disease-free survival.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Marrow Transplantation , Hodgkin Disease/therapy , Leukemia/therapy , Whole-Body Irradiation/adverse effects , Adolescent , Busulfan/adverse effects , Child , Child, Preschool , Cyclophosphamide/adverse effects , Etoposide/adverse effects , Female , Graft vs Host Disease/etiology , Humans , Infant , Male , Transplantation, Autologous , Transplantation, HomologousABSTRACT
60 patients undergoing bone marrow or stem cell transplantation were treated with liposomal Amphotericin-B for documented or suspected mycosis. 34 patients had a prior course of conventional Amphotericin-B with the following adverse effects: increasing creatinine above 1.4 mg/dl (n = 17), increasing creatinine below 1.5 mg/dl (n = 9), no response (n = 6), and clinical side-effects (n = 4). Liposomal Amphotericin-B failed in 6/7 patients with culture-proven mycosis who died from infection with Aspergillus (n = 2) and Candida (n = 4), respectively. One patient with Candida lambica sepsis was cured. No patient with clinically or serologically suspected or diagnosed infection died from mycosis. Liposomal Amphotericin-B was well tolerated in 57 patients, even after side-effects of the conventional formulation. Adverse effects occurred in three cases, requiring the withdrawal of the drug in one patient. Due to toxic side-effects of the high-dose therapy and transplant-related complications, it was difficult to evaluate the influence of liposomal Amphotericin-B on laboratory parameters. Eight patients showed a decrease of creatinine levels, which had increased above normal values under preceding therapy with conventional Amphotericin-B. Liposomal Amphotericin-B is well tolerated in patients undergoing high-dose therapy and bone marrow transplantation. The efficacy of liposomal Amphotericin-B needs to be investigated in randomized studies in comparison with conventional Amphotericin-B.
Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Amphotericin B/adverse effects , Antifungal Agents/adverse effects , Aspergillosis/complications , Aspergillosis/drug therapy , Child , Child, Preschool , Female , Humans , Infant , Lung Diseases, Fungal/complications , Lung Diseases, Fungal/drug therapy , Male , Middle Aged , Mycoses/complications , Mycoses/drug therapy , Neutropenia/complications , Opportunistic Infections/complications , Treatment OutcomeABSTRACT
Use of cryopreserved donor bone marrow may facilitate scheduling of allogeneic bone marrow transplantation (BMT) by affording independence of a fixed time for bone marrow donation. The potential risk of damage to hematopoietic stem cells by cryopreservation resulting in delayed engraftment or graft failure has to be taken into account, however. To address these issues, the outcome of 19 matched related BMT (1992-94) performed with cryopreserved donor bone marrow was analyzed and compared with 19 related BMT (1990-93) receiving fresh donor bone marrow (control group). Time to engraftment of patients receiving cryopreserved bone marrow was not different from the control group (ANC > 0.2 x 10(9)/l 15.5 +/- 3.8 days vs 15.8 +/- 5.0 days; ANC > 0.5 x 10(9)/l 17.3 +/- 4.1 days vs 17.9 +/- 5.0 days, respectively). We did not find the previously described trend toward a lower incidence of acute GVHD in patients receiving cryopreserved bone marrow compared with patients receiving fresh bone marrow (acute GVHD > or = II 78 vs 64%). Furthermore, the two groups did not differ in the incidence of chronic GVHD (55 vs 38%) or day 100 survival (74 vs 68%). We conclude that in allogeneic BMT cryopreserved bone marrow cells can be safely used without jeopardising or prolonging time to engraftment.
