Autologous Blood Progenitor Cell Transplantation Research Articles

Safety and Efficacy of Targeted-Dose Busulfan and Bortezomib as a Conditioning Regimen for Patients with Relapsed Multiple Myeloma Undergoing a Second Autologous Blood Progenitor Cell Transplantation

Patients with multiple myeloma (MM) who relapse after autologous transplantation have limited therapeutic options. We conducted a prospective, multicenter, phase IIa study to investigate the safety and efficacy of i.v. busulfan (Bu) in combination with bortezomib as a conditioning regimen for a second autotransplantation. Because a safe Bu exposure was unknown in patients receiving this combination, Bu was initially targeted to a total area under the concentration–time curve (AUC) of 20,000 μM × minute. As no concentration-limiting toxicity was observed in 6 patients, this Bu exposure was utilized in the following treatment cohort (n = 24). Individualized Bu dose, based on test dose .8 mg/kg pharmacokinetics (PK), was administered daily for 4 consecutive days starting 5 days before transplantation, followed by a single dose of bortezomib (1.3 mg/m2) 1 day before transplantation. The total mean dose of i.v. Bu (including the test dose and 4-day administration) was 14.2 mg/kg (standard deviation = 2.48; range, 8.7 to 19.2). Confirmatory PK demonstrated that only 2 of 30 patients who underwent transplantation were dosed outside the Bu AUC target and dose adjustments were made for the last 2 doses of i.v. Bu. The median age was 59 years (range, 48 to 73). Median time from first to second transplantation was 28.0 months (range, 12 to 119). Of 26 evaluable patients, 10 patients attained a partial response (PR) or better at 3 months after transplantation, with 2 patients attaining a complete response. At 6 months after transplantation, 5 of 12 evaluable patients had maintained or improved their disease status. Median progression-free survival was 191 days, whereas median overall survival was not reached during the study period. The most common grade 3 and 4 toxicities were febrile neutropenia (50.0%) and stomatitis (43.3%). One transplantation-related death was observed. A combination of dose-targeted i.v. Bu and bortezomib induced PR or better in one third of patients with MM who underwent a second autotransplantation, with acceptable toxicity.

Peripherally inserted central venous catheters for autologous blood progenitor cell transplantation in patients with haematological malignancies.

In contrast to the high risk of haemorrhage associated with the implantation of a central venous catheter (CVC) via the internal jugular or subclavian access, the use of a peripherally inserted catheter (PICC) offers the advantage of a lower risk of bleeding complications. However, the rate of phlebitis is higher with the PICC and its use has been declining. We have studied the benefits and adverse events of a new type of PICC and a common type. From October 1999 to October 2001, 70 PICCs (Olimpicc, Vygon, Germany, n=40; and LIFECATH-PICC(PUR)5FR Vygon, Germany, n=30) were inserted into 66 patients with haematological malignancies and used for high-dose chemotherapy, total parenteral nutrition and autologous blood stem cell transplantation. While removing the catheter, central and peripheral blood cultures were taken. The catheter tip was investigated by the semi-quantitative roll-out method of Maki. Sixty-five PICCs were removed after a median of 8.9 days. In five cases a catheter-associated significant colonisation with coagulase-negative staphylococci occurred. In two instances catheter-related bacteraemia was found. In our study this catheter system was inserted in 94% of patients without problems and showed a low incidence of phlebitis (5/65). Because of the high rate of catheter malfunction reported during and after our study, the Olimpicc catheter is no longer available. The PICC system, and the LIFECATH-PICC(PUR)5FR in particular, offers a safe and effective alternative for central venous access to the internal jugular vein.

Intramedullary spinal cord recurrence after high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation for limited-disease small cell lung cancer

Intramedullary spinal cord metastasis is very rare in small-cell lung cancer (SCLC), and develops in only 2% of neurological disorders associated with SCLC according to previous reports. We describe here a patient with SCLC who developed intramedullary spinal cord recurrence after high-dose chemotherapy (HDCT) followed by autologous blood progenitor cell transplantation (ABPCT). A 59-year-old Japanese male was referred to us for diagnosis and treatment of an abnormal shadow on a chest radiograph. Based on transbronchial biopsy and staging procedures, he was diagnosed with limited-disease (LD)-SCLC. He received concurrent chemoradiotherapy followed by late intensification with HDCT supported by ABPCT. He achieved complete response and was discharged after receiving prophylactic cranial irradiation (PCI). However 6 months later, he noticed rapidly progressive weakness of the left lower extremity and bowel/bladder dysfunction. Magnetic resonance imaging (MRI) of the spinal cord disclosed an intramedullary tumor exhibiting an enhancement effect with Gd-DTPA at the 11–12th level of the thoracic vertebra. Immediately, radiotherapy to the spinal cord metastasis was given at a dose of 30 Gy, and his neurological disorders were completely resolved. At this time of reporting, he is doing well without recurrence. This case indicates that intramedullary spinal cord is one of the recurrence sites implicated after HDCT and PCI in LD-SCLC.

Factors affecting both peripheral blood progenitor cell mobilization and hematopoietic recovery following autologous blood progenitor cell transplantation in multiple myeloma patients: a monocentric study.

The aim of the study was to analyze the factors influencing peripheral blood progenitor cell (PBPC) collection after high-dose cyclophosphamide (HDCYC) (7 g/m2) and hematopoietic recovery after autologous transplantation of HDCYC-mobilized PBPC (ABPCT) in 116 patients with aggressive multiple myeloma (MM). Following HDCYC 74 patients received hematopoietic growth factors (HGF), either G-CSF (n = 19) or GM-CSF (n = 55). All the patients were subsequently planned to undergo ABPCT. PBPC collection was possible for 106 patients. The most important prognostic factor for collection of more than 25 x 10(4) CFU-GM cells/kg and 2 x 10(6) CD34+ cells/kg was the use of HGF (P = 0.002 and 0.009, respectively). Previous use of an alkylating agent, response to treatment before HDCYC, and interval between diagnosis and HDCYC were also significant factors (P = 0.004, 0.025 and 0.001, respectively). The number of CFU-GM cells infused was the most important parameter for rapid and complete hematological recovery after ABPCT (P < 0.0001). Thus the use of HGF post-HDCYC is the major factor which, associated with reduced time between diagnosis and HDCYC and the use of an alkylating agent, could increase the numbers of hematopoietic progenitors collected, and subsequently improve hematopoietic recovery following ABPCT in MM patients.

Blast counts in blood progenitor cell (BPC) correlate with CD34+ cells and CFU-GM and are useful predictor of haemopoietic recovery after autologous BPC transplantation collections.

Assessment of the quality of blood progenitor cell (BPC) collections is based mainly on CD34+ cell enumeration by flow cytometry, or scoring of granulocyte-macrophage colony-forming cells (CFU-GM). A minimum cell dose for haemopoietic recovery can be defined by both assays; however, the CFU-GM assay can not be used for 'real-time' decisions, whereas CD34+ cell scoring requires facilities and expertise which are not universally available. We have investigated the possibility of using morphologically defined blast cells within BPC harvests as a surrogate marker of harvest haemopoietic stem/progenitor cell content, as well as their correlation with CD34+ cells and CFU-GM within the harvests. We have found that blast counts correlate strongly with both CD34+ cell counts and CFU-GM within BPC harvests, as well as with time to granulocyte and platelet recovery after autologous BPC transplantation (ABPCT). Furthermore, we have defined a threshold value of 1.3 x 10(6)/kg blasts, above which there is a high probability of rapid haemopoietic recovery after ABPCT. We conclude that blast count is a simple, rapid and reliable method of assessing BPC harvest quality.

Peripheral Blood Progenitor Cell Collection during Hematopoietic Recovery following Autologous Blood Progenitor Cell Transplantation

Peripheral Blood Progenitor Cell Collection during Hematopoietic Recovery following Autologous Blood Progenitor Cell Transplantation

12 Multiple courses of high-dose alkylating therapy with autologous stem cell support

Since the introduction of autologous blood progenitor cell transplantation, (APCT) bone marrow suppression is no longer dose-limiting after high-dose therapy. We have developed a high-dose chemotherapy regimen ‘CTC', that includes cyclophosphamide (6g/m²), thiotepa (480mg/m²) and carboplatin (1600mg/m²) administered over four days. This regimen has been shown to be well-tolerated in over 80 (first) courses and multiple courses could be feasible. 28 patients received 2 courses of CTC, CTC-2 beginning on day 28 after the first APCT. One patient died of sepsis, one developed reversible veno-occlusive disease (VOD). Eleven patients received 3 subsequent courses of CTC. There were three toxic deaths: 1 × sepsis, 1 × VOD, 1 × hemolytic uremic syndrome (HUS). Two other patients developed reversible VOD, one had reversible HUS. While two closely spaced CTC courses are feasible, three subsequent courses are associated with frequent unacceptable organ toxicity. Preliminary data of a phase I/II study in advanced breast cancer suggest that three tightly spaced ‘tiny CTC' courses—containing 2/3 of the doses of each of the agents in a standard CTC course—may be well tolerated and are not associated with excess organ toxicity.