Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD.

Extracorporeal photopheresis (ECP) was given to 23 patients with steroid-refractory acute GVHD (aGVHD, grade II (n=10), III (n=7) or IV (n=6)). The median duration of ECP was 7 months (1-33) and the median number of ECP cycles in each patient was 10. Twelve patients (52%) had complete responses. Eleven patients (48%) survived and 12 died, 10 of GVHD with or without infections and two of leukaemia relapse. The average grade of GVHD was reduced from 2.8 (on the first day of ECP) to 1.4 (on day +90 from ECP) (P=0.08), and the average dose of i.v. methylprednisolone from 2.17 to 0.2 mg/kg/d (P=0.004). Complete responses were obtained in 70, 42 and 0% of patients, respectively, with grades II, III and IV aGVHD; complete responses in the skin, liver and gut were 66, 27 and 40%. Patients treated within 35 days from onset of aGVHD had higher responses (83 vs 47%; P=0.1). A trend for improved survival was seen in grade III-IV aGVHD treated with ECP as compared to matched controls (38 vs 16%; P 0.08). ECP is a treatment option for patients with steroid refractory aGVHD and should be considered early in the course of the disease.

Double plateletpheresis (DPA) and tailored RBC collection with the Excel-Pro: preliminary results.

The Dideco Excel-Pro is frequently used for double plateletpheresis (DPA) when the platelet precount exceeds 280 x 10(3)/l. Platelets are collected as "dry platelets" and the resuspension solution is added when the procedure is over. Even when DPA is carried out the product volume prior to resuspension may be as low as 60 ml. As a result, a third product may be collected along with platelets. Our priority is to collect RBCs and, depending on the donor's BW, tailored RBC collections are carried out. This means that from 400 to 480 ml of PRBC (70% hct) are collected from donors whose BW exceeds 75 kg. The results of the last 27 DPA/tailored PRBC collections are: Donors gender and BW (kg), 19M/8F: 88.4 +/- 7.3 Hemoglobin (g/dl): 15.4 +/- 1.3 Platelet precount (x 10(3)/microl): 308 +/- 45 Volume of blood processed (1): 5.5 Procedure time (min): 81 +/- 3 Platelet yield (x 10(11)): 6.8 +/- 0.6 Avg Hemoglobin content of PBRC (g): 102.6 +/- 12.3 WBC contamination of the platelets: 6.8 +/ -10(5).

Adjuvant chemotherapy with high-dose cyclophosphamide, etoposide and cisplatin intensification without progenitor cell support in breast cancer patients with ten or more involved nodes: 5-year results of a pilot trial.

OBJECTIVES: The purpose of this study was to evaluate the clinical efficacy and tolerability of high-dose (HD) chemotherapy with growth factor support in primary breast cancer with extensive nodal involvement. PATIENTS AND METHODS: Fifty-three patients with ten or more involved nodes were recruited and were given three cycles of standard-dose fluorouracil, epidoxorubicin and cyclophosphamide followed by one single course of high-dose CEP (cyclophosphamide, etoposide and cisplatin). No autologous progenitor support was used. RESULTS: Five-year actuarial disease-free and overall survival were 40 and 60%, respectively. High-dose CEP required a median of 22 days of hospitalization and was associated with grade G3--4 nausea and vomiting in two thirds of the cases. Hematological toxicity was comparable to that of high-dose therapies delivered with autologous progenitor support. No therapy-related mortality was observed. CONCLUSIONS The efficacy of treatment was comparable to the best results of conventional therapy, with only a trend for improved survival. High-dose CEP was feasible with acceptable toxicity. Although this regimen does not require stem cell harvesting and storage, it requires clinical support comparable to autotransplantation procedures and side effects are not so manageable to recommend its use outside specialized units.

Cascade filtration (CF) with the Haemonetics MCS+: a new technical adaptation.

CF was introduced in clinical medicine in 1980. Up to now, exclusively two-vein procedures have been carried out with some limitations to expansion of this technique. In this report we describe the very first application of single-needle CF carried out with Haemonetics MCS + apparatus. Twenty procedures were completed without any untoward effect in patients suffering from TTP, post-hepatitic cryoblobulinemia, familial hypercholesterolemia and acute Guillan-Barrè Syndrome. From 1 to 4 sessions were carried out per patient with the expected laboratory and clinical results. The only limit is the procedure time that averages 231 +/- 48 min., approximately 40% longer than two needle procedures.

The MCS + revision A2 for highly efficient PBSC collection.

Autologous PBSC transplantation is an integral component of the management of hemato-oncology patients. In order to reduce the number of sessions needed to collect the desired number of repopulating cells there has been significant research activity in developing progressively more and more effective technologies and techniques. Recently our group has been involved in the rejuvenation of the MCS + apparatus for both platelet and PBSC collection. The so called "version A2 protocol" is aimed at collecting PBSC in a very efficient way. This protocol is characterized by high blood flow rates both in the collection and reinfusion (80 ml/min) recirculation (56 ml/min) and collection phases (30 ml/min). Only one recirculation is carried out every 5 cycles and only from 5 to 7 are carried out for a single procedure. Twenty-seven collections were carried out of which 25 were evaluable in terms of PBSC efficiency. These averaged 68.8% in an average procedure time of 3.5-5 h for processing an average of 7,052 ml of blood. The RBC contamination was reduced to approximately 5.02 g of hemoglobin and the average volume of the product to 177 ml. If these results are confirmed, the gap between CFC and DFC PBSC is progressively closing.

Effects of three cytokine regimens on hematologic recovery and progenitor cell mobilization after high-dose cyclophosphamide, etoposide, and cisplatin.

The aim of this study was to compare both the effects on hematologic recovery and circulating progenitor cell mobilization and the toxicity of three cytokine regimens administered after high-dose non-myeloablative chemotherapy with cyclophosphamide 5 g/m(2), etoposide 1.5 g/m(2) and cisplatin 150 mg/m(2). Thirty-five consecutive patients were non-random sequentially allocated to one of three treatment groups: (1) granulocyte colony-stimulating factor alone (n = 15); (2) granulocyte-macrophage colony-stimulating factor alone (n = 10), and (3) sequential interleukin-3 and granulocyte-macrophage colony-stimulating factor (n = 10). Neutrophil recovery in group 1 was significantly hastened as compared to the two other groups (median 2 days, p < 0.005), while no significant differences were observed between groups 2 and 3. CD34+ cells peaked about 2 days earlier in group 1 compared to the other groups (p = 0.0001), whereas the median peak value of CD34+ cells was similar in the three groups. In all patients, the toxicity related to cytokine administration was low and easily manageable with nonsteroidal anti-inflammatory drugs.

Comparative effects of three cytokine regimens after high-dose cyclophosphamide: granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), and sequential interleukin-3 and GM-CSF.

PURPOSE: To compare the toxicity and effects on hematologic recovery and circulating progenitor cell mobilization of three cytokine regimens administered after high-dose cyclophosphamide (HD-CTX; 6 g/m(2)), given as the first step of a high-dose sequential chemotherapy. PATIENTS AND METHODS: Forty-eight patients with breast cancer or non-Hodgkin's lymphoma were randomized to receive granulocyte colony-stimulating factor (G-CSF) alone (arm 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) alone (arm 2), or sequential interleukin-3 (IL-3) and GM-CSF (arm 3). Cytokines were administered as a single daily subcutaneous injection at a dose of 5 to 6 microg/kg/d. Progenitor cells were evaluated in peripheral blood as well as in apheretic product as both CD34(+) cells and granulocyte-macrophage colony-forming units (CFU-GM). RESULTS: Neutrophil recovery was faster in arm 1 as compared with arms 2 and 3 (P <.0001); no significant differences were observed between arms 2 and 3. In arm 3, a moderate acceleration of platelet recovery was observed, but it was statistically significant only as compared with arm 1 (P =.028). The peak of CD34(+) cells was hastened in a median of 2 days in arm 1 compared with arms 2 and 3 (P =.0002), whereas the median peak value of CD34(+) cells and CFU-GM was similar in the three patient groups. Administration of IL-3 and GM-CSF resulted in more significant toxicity requiring pharmacologic treatment in 90% of patients. CONCLUSION: The three cytokine regimens administered after HD-CTX are comparably effective in reducing hematologic toxicity and mobilizing the hematopoietic progenitor cells. G-CSF accelerates leukocyte recovery and progenitor mobilization. Although G-CSF-treated patients have somewhat slower platelet recovery, they definitely have fewer side effects.

Standard-dose recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows safe and repeated administration of high-dose cyclophosphamide, etoposide, and cisplatin (CEP).

High-dose chemotherapy often requires hematopoietic progenitor cell reinfusion, but drugs with extramedullary dose-limiting toxicity may be administered in the high-dose range by simple growth factor support. In this study, we evaluated the feasibility and toxicity of a three-drug high-dose regimen supported by recombinant human granulocyte colony-stimulating factor (rhG-CSF). Ten patients with histologically proven malignancy were enrolled. Eight had breast cancer, one non-Hodgkin's lymphoma, and one a mediastinal tumor of unknown origin. The regimen included cyclophosphamide (C) 5 g/m2, etoposide (E) 1.5 g/m2, and cisplatin (P) 150 mg/m2 (CEP), administered in a 3-day schedule followed by rhG-CSF, 300 micrograms once a day, beginning from day +5 (36 h after the end of chemotherapy). The cycle was repeated as clinically needed up to three times. After the first course, hematologic recovery was rapid and complete without documented infections, and no relevant extramyeloid toxicities were observed. Eight of 10 patients received a second course with comparably low toxicity, and three of them received a third course. We concluded that CEP therapy can be administered safely and even repeatedly, by simple growth factor support, in good performance status cancer patients.