Summary:thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerDonor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone ated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use marrow transplantation (BMT). Severe graft-versushost disease and prolonged periods of pancytopenia of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted some of the problems associated with DLI. Relapse of leukemia after allogeneic bone marrow transplete clinical and molecular remission for time periods plantation (BMT) is a serious event putting the patient at between 1 and 12 months. Six of six patients with acute an immediate risk of death. Due to patients' poor general leukemias achieved a complete remission. All of them condition, a second myeloblative therapy followed by transrelapsed after a median remission duration of 24 weeks plantation of hematopoietic cells is often not possible and (range 11-49 weeks). Three patients relapsed at extracannot generally be recommended because it is associated medullary sites (CNS, testes, skin). Four of six acute leuwith a high rate of life-threatening toxicity. 1,2 Other kemia patients received further cytoreductive therapy.approaches to treat relapse after BMT have also shown limAll patients responded again and are in complete ited benefit. 3,4 In contrast, the infusion of donor lymphoremission for time periods between 14 and 615 days.cytes as a novel way of adoptive immunotherapy proves to Two patients with acute leukemias have died due to disbe highly effective in a substantial number of patients. Up semination of the disease. The patient with MM did not to 70% of patients with chronic myeloid leukemia (CML) respond and is alive with disease. Severe (grade III) and approximately 30% of patients with acute myelocytic acute GVHD developed in two of 11 patients, three leukemia (AML) respond favorably to this treatment patients developed grade II disease, six patients did not modality and some of them sustain long-lasting second show any signs of GVHD. Extensive chronic GVHD has remissions. 5-11 However, the infusion of donor leukocytes developed in two cases to date. Patients with chemois not without problems. Profound and protracted periods therapy prior to PBPC infusion developed neutropenia of pancytopenia complicate the procedure in more than a and thrombocytopenia with a maximum duration of 20 third of patients so tr...
Procurement of a high number of progenitor cells is of primary interest in allogeneic PBSC transplantation. We have retrospectively compared toxicity, mobilization effect and progenitor cell yields of two different rhG‐CSF schedules in 11 consecutive healthy individuals donating their PBSC. Five of them received rhG‐CSF 16 μg/kg/d for 4 subsequent d in 2 divided subcutaneous injections (group A); similarly, 6 donors received rhG‐CSF 10 μg/kg/d for 5 d (group B). The aphereses were started the last day of rhG‐CSF treatment; 9 donors underwent 2 aphereses, one underwent 1 and another 3 procedures, always on subsequent days. Toxicity was mild, but moderate thrombocytopenia developed following apheretic collections, irrespective of rhG‐CSF schedule. In all the donors WBC, as well as circulating CD34+ cells, CFU‐GM, CFU‐GEMM and BFU‐E dramatically increased over the baseline values, peaking on d 5 or 6, with no statistical difference between the 2 groups for the height of the cell peaks. Also the peripheral lymphoid cell populations (CD3+, CD19+ and CD56+/CD3‐) increased following the rhG‐CSF administration. The number of MNC, CFU‐GM, BFU‐E, CFU‐GEMM, as well as CD34+, CD3+, CD19+ and CD56+/CD3 cells collected by apheresis showed no statistical difference in the 2 groups. Overall, 8 of the 11 donors collected the target number of CD34+ cells > 4times106/kg ideal recipient body weight with the first apheresis, with no difference between the 2 groups. Mobilization with rhG‐CSF in healthy donors enables the collection of large number of progenitor cells with modest side effects. A schedule of 10 μg/kg for 5 d is as effective as 16 μg/kg for 4 d. A single apheresis would be enough in 80% of cases.
IntroductionAt Hiwa Cancer Hospital (Sulaymaniyah, Iraqi Kurdistan) after the center was started by a cooperative project in June 2016, autologous transplantation was developed.Patients and MethodsTo develop the project, the capacity-building approach was adopted, with on-site training and coaching of personnel, educational meetings, lectures, on-the-job training, and the implementation of quality management planning.ResultsHere, we report initial results of peripheral-blood stem-cell mobilization and collection of the first 27 patients (age 12 to 61 years; 19 males and 8 females; multiple myeloma, n = 10; plasma cell leukemia, n = 1; Hodgkin lymphoma, n = 12; non-Hodgkin lymphoma, n = 3; and acute myeloid leukemia, n = 1). Only three (11.5%) of 26 patients experienced a failure of mobilization. A median of 6.1 × 106/kg CD34-positive cells per patient were collected (range, 2.4 to 20.8), with two apheretic runs. Twenty-four patients underwent autologous transplantation. All but one transplantation engrafted fully and steadily, with 0.5 and 1.0 × 109/L polymorphonucleates on day 10.5 (range, 8 to 12) and day 11 (range, 9 to 15), respectively, and with 20 and 50 × 109/L platelets on day 13 (range, 10 to 17) and day 17 (range, 2 to 44), respectively. More than 95% of patients are projected to survive 1 year after autograft.ConclusionThese data are the result of an Italian effort to establish in Iraqi Kurdistan a leading center for hemopoietic stem-cell transplantation. The capacity building approach was used, with on-site training and coaching as instruments for the development of provider ability and problem solving. With future limitations for immigration, this method will be helpful, especially in the field of high-technology medicine.
We report the preliminary results of a study exploring the possibility of collecting circulating progenitor cells (PBSC) with a protocol based on the administration of single doses (4 g/m2) of cyclophosphamide and G-CSF (5 or 10-micrograms/kg) in 9 patients with non Hodgkin's lymphoma. The peak level of CD34+ cells occurred after a median of 10 days (range 8-11), generally coinciding with the median peak level of CFU-GM, with a mean 31.27 fold increase above basal levels. 3 (range 2-5) leukaphereses were required to harvest a median number of 25.1 x 10(4)/kg (8-105) CFU-GM and of 9.4 x 10(6)/kg (1.2-25) CD34+ cells. No difference was recorded between 5 and 10 micrograms/kg of G-CSF in terms of PBSC yield. In transplanted patients, a strong correlation was found between CD34+ cells infused/kg and platelet recovery (r = -0.8, p = 0.002). No toxicity was observed and apheretic procedures were regularly performed outpatiently. Our conclusion is that this protocol is particularly suitable for an outpatient treatment/collection program.
In the present study we assess the antitumor effect and circulating stem cells (CSC) mobilizing capacity of high-dose cyclophosphamide (5 to 7 gr/m2, HDCY). This treatment was given to 21 patients with various hematologic malignancies (8 NHL, 5 MM, 4 HD, 3 CML) excluding 1 with neuroblastoma. All were eligible for later autologous blood stem cell transplantation (ABSCT). To reduce the hematologic toxicity of HDCY, GM CSF was simultaneously administered in 5 patients. HDCY produced a response (as defined by a > 50% reduction of previous tumor mass) in 3 out of 12 HD/NHL and 1 out of 3 MM. Patients with CML were not considered to be evaluable for tumor response. Cell collection yields after HDCY varied widely with a range of 1.5 to 169.9 x 10(4)/Kg (median 13.1) CFU-GM and 1.7 to 18.4 x 10(8)/Kg (median 5.8) MNC collected per patient. Hematologic recovery was rapid and sustained with a median of 16 (12-18) days to PMN > 0.5 x 10(9)/L and 14 (11-18) days to Plt > 100.0 x 10(9)/L. Granulocyte recovery was significantly faster after GM-CSF (13 vs 16 days to PMN > 0.5, p = 0.0008). Non hematologic toxicity consisted mainly of nausea and vomiting, but fatal complications occurred in 2 patients, from pulmonary infection in one and from tumor-lysis syndrome in the other. HDCY represents a useful means of increasing collection of CSC, but toxicity is not irrelevant. Whether a similar anti-tumor effect and mobilizing capacity would be offered by single lower intermediate doses of the drug is still to be ascertained.
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