Long-term haematological recovery following high-dose chemotherapy with autologous bone marrow transplantation or peripheral stem cell transplantation in patients with solid tumours

Abstract

Summary:Long-term peripheral blood counts and factors influencing long-term trilineage haematological recovery of consecutive patients in a single institution treated with high-dose chemotherapy (HDC) and ABMT or PSCT for solid tumours were examined. Patients with a relapse-free survival of Ͼ1 year were included in the analysis (n = 131). Peripheral blood counts were examined 6 months and yearly following transplantation. Median follow-up was 4.1 years (range 1-10+ years). Three years after transplantation 91% of patients had normal white blood counts (WBC), 94% normal haemoglobin (Hb) and 75% normal platelets. Trilineage recovery was complete in 70% (n = 83) at 3 years and 85% pheral blood has been increasingly applied for a variety of disorders. Autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PSCT) permits the delivery of a higher, marrow-ablative dose of chemotherapy. In addition to patients with haematological diseases an increasing number of patients with solid tumours have undergone HDC with ABMT or PSCT during the last decade. 1 HDC with ABMT or PSCT is not considered standard treatment for solid tumours, therefore benefits have to be studied in randomised studies and balanced against the risks of the treatment, both in the short and long term. 2 Solid tumours treated with HDC followed by ABMT or PSCT include breast cancer, 3,4 ovarian carcinoma, 5-7 relapsed germ cell tumours 8-10 and childhood sarcomas. 11,12 In the last decade, a shift from bone marrow to peripheral blood as the source of haematopoietic stem cells has occurred. It has been shown that PSCT compared to ABMT offers faster short-term recovery of peripheral blood counts resulting in lower morbidity, mostly due to fewer infections and haemorrhagic periods and a reduced usage of blood products. 13 Abnormalities in haematopoiesis have been shown following transplantation. 14-17 Decreased bone marrow cellularity has been shown to persist up to 3 years following allogeneic transplantation. 18 The number of colony-forming units (CFU-GM, BFU-E, CFU-Meg and TL-CFU) was shown to be diminished following autologous transplantation persisting for as long as 4-5 years. [19][20][21][22] Patients relapsing after transplantation showed decreased haematological tolerance to reinduction chemotherapy. 23 Radiotherapy after transplantation and infections during followup can lead to haematopoietic stress and temporary cytopenias have been described in such circumstances. 24 Clinical problems could therefore arise from the abnormalities in haematopoiesis following autologous transplantation.Data about attaining and maintaining sustained long-term (ie Ͼ1 year) haematopoiesis following ABMT or PSCT are scarce. Some data are available from patients with haematological malignancies and/or after allogeneic transplantation with, in general, a follow-up of 1 year at the most. 18,25,26 Studies usually report that peripheral blood counts will normalise within 1 year after transplantation. 21,23,24,[27][28][29][30][31][32] Factors in...

Loss of quiescence and impaired function of CD34+/CD38low cells one year following autologous stem cell transplantation

“…Apparently, the applied chemotherapy and ASCT have resulted in an impaired chemotoxic stress response of the bone marrow cells. 6,7 These findings are in line with our recent observations demonstrating a shift within the CD34 + progenitor cell compartment post-ASCT towards phenotypically defined granulocyte/macrophage progenitors (GMPs), which coincided with a reduced clonogenic potential and enhanced cell cycle activity. 8 After allogeneic stem cell transplantation, a higher cycling activity of CD34 + CD90…”

Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

“…The maximum myelosuppression at t 1 and the (partial) haematological recovery at t 2 , indicate haematopoietic proliferative stress at the time-point at which TRF length was measured (at t 1 ). Full recovery of haematological parameters after this highdose treatment may actually take years (Nieboer et al, 2000), and the impact of this lengthy process on TRF length changes at later time-points than t 1 is currently being studied.…”

Outcome of 67 patients with solid tumors relapsed after high-dose chemotherapy and peripheral blood stem cell transplantation

“…Therapy should be performed according to established risk-adapted algorithms for metastatic disease, particularly in patients with breast cancer. 19 Since patients with solid tumors were shown to have slow trilineage hematological recovery, 20 bone marrow toxicity of subsequent chemotherapy must be taken into account. Leukocytopenia and thrombocytopenia grades 3 and 4 occurred in 61 and 75% of all patients, respectively, and was most pronounced in patients with testicular cancer, while nonhematological toxicity did not differ from that seen in other patients.…”

“…After HDC and PBSC transplantation, patients with breast cancer recovered their WBC and platelets at day 11 (range 9-16) and day 12 (10-25), respectively. The corresponding values for patients with ovarian cancer were day 10 (range 8-13) and 11 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)) and for those with testicular cancer day 11 (range 8-13) and 12 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), respectively. There was no correlation between the number of HDC courses or WBC and platelet engraftment and survival (r À0.30 to +0.32 for any correlation).…”