Early and Late Complications in 247 Adult Autologous Stem Cell Transplant Recipients.

High-dose therapy supported by autologous stem cell transplantation (ASCT) has became a widely applied therapy in many haematological malignancies during two decades.

ASCT may be curative and even more commonly leads to prolonged survival.

Along with the use of mobilised blood progenitor cells and improved supportive care after ASCT, the early treatment-related mortality (<100 d) has declined and is now in the order of 2–3%. Although relapse or progression of underlying malignancy is the most common cause of death in ASCT recipient, also late (>100 d) non-relapse mortality (NRM) occurs.

We have analysed a cohort of 191 patients (108 male and 83 female) who received ASCT (247 transplant) in 1994–2005 in Bone Marrow Transplant Unit of San Gerardo Hospital.

The median age was 49 years (16–70).

The most common diagnoses included lymphoma (88), multiple myeloma (67), acute leukemia (32), chronic lymphocitic leukemia (2) and myelodysplastic syndrome (2).

At the time of transplant (247 transplant) 93 patients was in complete remission, 67 patients in partial remission and 86 patients in persistent/progression malignancies.

The most common conditioning treatment ASCT included: Melphalan (200 mg/m2 or 140 mg/m2) in 55% of case, BEAM in 30%, Busulfan-Cyclophosphamide in 4%, others in 11% (Thiotepa- Cyclophosphamide, Busulfan-melpalan, Mitoxantrone-melphalan, TBI- Cyclophosphamide).

The median dose of CD34+ reinfused was 5.21 × 10^6/kg (1.2–15 × 10^6/kg).

The median time to achieve an absolute neutrophil count >0.5 × 10^9/l was 12 days (range 0–49) and to achieve a platelet count > 20 × 10^9/l was 19 (range 0–36).

The median time of hospitalisation was 22 days (range 10–93).

During hospitalisation 158 patients (63%) developed oral mucositis: 100 (53%) of them developed mucosites of grade 1–2, 58 (37%) of grade 3–4. High dose chemotherapy with BEAM was more toxic on the oral mucose than high dose of Melphalan alone. In 41% of patients total parenteral nutrition support was necessary.

During hospitalisation 180 patients (73%) developed sepsis: possible infection 61%, Gram + 20%, Gram − 12%, miscellaneous 3%, fungi 2%, viral 1%, Pneumocistis Carinii 1%.

Regimens including cyclophosphamide was responsible for most sepsis.

44 patients presented a positive antigenemia of Cytomegalovirus; all of them were seropositive for CMV before ASCT; only one case of primary infection was seen and this patient died after 55 days after ASCT.

At 100 days from ASCT 173 patients were in complete remission, 53 of them had a relapse of hematologic malignancies in a median time of 1 year (range 51 days-6 year), 32 patients in partial remission and 35 patients in persistent/progression malignancies.

The late complications were: cardiac (30%), hepatic (16%), renal (3%), gastrointestinal (12%), CNS (8%), other (MGUS, cataract, aseptic necrosis of bone, diabete)(31%).

The most important cardiac complications were: atrial fibrillation, sinusal tachycardia, arrhythmia, pericarditis. 61 patients (32%) died after ASCT.

Death was due to complications related to disease progression in 62% of patients. 25% of patients died from infections.

Secondary malignancies (acute myeloid leukemia) were the cause of late non relapse mortality in 2 patients.

Fatal cardiovascular complications were observed in 4 patients (acute myocardial infarction or cardiomyopatia most probably due to previous anthracycline therapy).