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S Vasta

Publications and source records attributed to S Vasta.

At least 19 recordsLinked to original sources
PubMed1997

Successful engraftment of allogeneic PBSC after conditioning with busulfan alone.

A 44-year-old woman with AML, while receiving a conditioning treatment with BU-CY for an allogeneic sibling transplant, developed septic shock with pulmonary embolism and heart failure. Conditioning was stopped at the end of the busulfan course and cyclophosphamide omitted. After antibiotics, dopamine and steroids the patient was allografted, using the donor's G-CSF-primed PBSC. She recovered her peripheral blood counts promptly and developed an acute GVHD grade II that responded to steroids. The DNA microsatellite analysis showed full donor engraftment up to a year from transplantation. This case suggests that the use of PBSC may facilitate engraftment in the absence of an effective immunosuppression during conditioning.

Adult↗
PubMed1997

Allogeneic peripheral blood progenitor cells for treatment of relapse after bone marrow transplantation.

Donor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone marrow transplantation (BMT). Severe graft-versus-host disease and prolonged periods of pancytopenia compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent some of the problems associated with DLI. Eleven patients (median age 41 years) received a total of 20 donor cell infusions. Their diagnosis was CML in hematological (two patients) or cytogenetic relapse (two patients), six patients suffered from acute myeloid leukemia (AM; n = 5) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+). One patient had multiple myeloma (MM). All six patients with acute leukemias received cytoreductive therapy prior to PBPC infusions; three patients with CML were pretreated with IFN alpha. Four of four patients with CML responded to PBPC infusions and currently are in complete clinical and molecular remission for time periods between 1 and 12 months. Six of six patients with acute leukemias achieved a complete remission. All of them relapsed after a median remission duration of 24 weeks (range 11-49 weeks). Three patients relapsed at extramedullary sites (CNS, testes, skin). Four of six acute leukemia patients received further cytoreductive therapy. All patients responded again and are in complete remission for time periods between 14 and 615 days. Two patients with acute leukemias have died due to dissemination of the disease. The patient with MM did not respond and is alive with disease. Severe (grade III) acute GVHD developed in two of 11 patients, three patients developed grade II disease, six patients did not show any signs of GVHD. Extensive chronic GVHD has developed in two cases to date. Patients with chemotherapy prior to PBPC infusion developed neutropenia and thrombocytopenia with a maximum duration of 20 and 14 days, respectively; prolonged periods of neutropenia did not occur. Two patients developed long-lasting thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted in only limited duration of cytopenia. The usage of PBPC infusion instead of non G-CSF-mobilized donor cells for treatment of relapse after BMT may reduce pancytopenia-related complications and merits further investigation.

Adult↗
PubMed1997

Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24 patients.

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x 10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2 to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day 13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU-GM number in the inoculum and time to hematologic reconstitution. Acute GVHD (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18 evaluable (55%) patients. We found no relationship between occurrence of acute or chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7 died after transplantation. Fifteen patients are currently alive and disease-free 67 to 710 (median 286) days from the graft. Allogeneic transplantation with unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence and severity seems comparable to that of bone marrow transplantation, but there may be an increase in chronic GVHD, mainly of the extensive form.

Adolescent↗
PubMed1996

Mobilization and collection of PBSC in healthy donors: comparison between two schemes of rhG-CSF administration.

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 micrograms/kg/d for 4 subsequent d in 2 divided subcutaneous injections (group A); similarly, 6 donors received rhG-CSF 10 micrograms/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 > 4 x 10(6)/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 micrograms/kg for 5 d is as effective as 16 micrograms/kg for 4 d. A single apheresis would be enough in 80% of cases.

Adolescent↗
PubMed1996

High incidence of chronic GVHD after primary allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies.

To assess feasibility and potential advantages of PBSC allograft, we transplanted nine patients (age 20-47 years) with advanced or poor-risk hematologic malignancies. These included eight HLA-identical sibling transplants and one partially matched. Cells were collected from donors by apheresis after rh-G-CSF 10-16 micrograms/kg/day for 4-5 days, and stored at 4 degrees C until infusion. Patients were conditioned with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg, and received GVHD prophylaxis with CSA-MTX. The graft consisted of PBSC alone, with a median of 101.2 (range 28-254.2) x 10(4)/kg CFU-GM, 6.84 (range 4.57-15.9) x 10(6)/kg CD34+ cells and 2.5 (range 1.2-6) x 10(8)/kg CD3+ cells. An ANC > 0.5 x 10(9)/1 occurred on (median) day 13 range 11-17), and a platelet count > 50 x 10(9)/l on (median) day 15 (range 12-29) post graft. One patient died of ARDS on day 13, the others are alive 96-485 (median 245) days from the graft. Two patients have relapsed, one of them with isolated CNS involvement. Acute GVHD (grade I-II) occurred in three patients and severe chronic GVHD in six patients, with no relationship to CSA withdrawal. This unexpected incidence of chronic GVHD might be linked to the high number of CD3+ cells in the graft, contributing to a favourable GVL effect.

Adult↗
PubMed1994

High-dose cyclophosphamide for mobilization of circulating stem cells in chronic myeloid leukemia.

Experimental and clinical data suggest that Ph-negative myeloid progenitor cells are present, albeit suppressed, in the bone marrow of chronic myeloid leukemia (CML) patients. These residual Ph-negative cells might, in certain circumstances, regain their proliferative advantage over the leukemic Ph-positive clone. Treating CML patients with intensive chemotherapy might allow the harvest, in the early phase of recovery, of Ph-negative stem cells to be used as graft after myeloablative regimen. In our study, 6 CML patients were admitted to a program of autograft with circulating stem cells (CSC) collected after high-dose (5 or 7 g/m2) cyclophosphamide (HD-CY) mobilization. All were autografted, using busulphan 16 mg/kg and melphalan 60 mg/m2. As graft, 4 patients received CSC only, while 2 patients were also given bone marrow, as their peripheral blood CFU-GM yield was unsatisfactory. Two previously alpha-IFN-responding patients showed a slow hematologic recovery, but achieved a marked and further reduction of their Ph-positive metaphases post-graft. Moreover, in one of them, cytogenetic analyses performed on apheresis product showed a more pronounced reduction of his Ph-positive metaphases, as compared to bone marrow samples, suggesting a potential purging effect of the mobilization procedure.

Adolescent↗
PubMed1994

High dose cyclophosphamide: stem cell mobilizing capacity in 21 patients.

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.

Adolescent↗
PubMed1993

High-dose cyclophosphamide, etoposide and BCNU (CVB) with autologous stem cell rescue in malignant lymphomas.

Eighteen patients with malignant lymphoma, 10 non-Hodgkin's and 8 Hodgkin's, were treated with high-dose CVB (cyclophosphamide 4 x 1.5 g/m2, etoposide 4 x 250-400 mg/m2, carmustine 4 x 150-200 mg/m2), followed by autologous peripheral blood stem cells (PBSC, 13 patients) or bone marrow (BM, 5 patients) transplantation. At the time of autograft 6 patients were in complete remission (CR), 3 in partial remission (PR) and 5 in relapse (4 sensitive, 1 resistant), whereas 4 had progressive disease. All CR patients had poor prognostic features at presentation. PBSC were collected at the time of rapid hematologic recovery after intense chemotherapy by means of a cell separator. All patients engrafted. Median time to achieve > or = 0.5 x 10(9)/l polymorphonuclear cells (PMN) and > or = 50 x 10(9)/l platelets was 13 days for both cell types in PBSC autografted patients, versus 20 and 28 days respectively in BM autografted patients. A significant advantage of PBSC over BM was found in terms of time needed to recover either PMN > or = 0.5 and PMN > or = 1 x 10(9)/l (p = 0.01). Autograft-related toxicity consisted mainly of moderate severity interstitial pneumopathy (3 patients), and veno-occlusive disease (1 patient) that resolved completely. Of the 12 patients autografted with detectable disease, 6 (50%) obtained a CR. Seven out of 18 autografted patients (39%) had disease progression within 1 to 5 months of autograft. The projected progression-free survival is over 50% at 4 years and it was significantly longer in patients with sensitive disease than in those with resistant disease (p = 0.01). The efficacy and the low toxicity of CVB suggest that autograft with PBSC may be proposed for the primary treatment of poor prognosis malignant lymphomas.

Adult↗
PubMed1993

Cyclophosphamide 4 g/m2 plus rhG-CSF for mobilization of circulating progenitor cells in malignant lymphomas.

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.

Adult↗
PubMed1991

Treatment of malignant lymphomas with very-high-dose CVB followed by transplantation of autologous blood stem cells collected after mobilizing chemotherapy.

In 8 patients (age 25 +/- 46 years, mean 34.5), 4 with Hodgkin's disease (HD) and 4 with non-Hodgkin's lymphoma (NHL), circulating stem cells (CSC) collected at the time of rapid leukocyte and platelet recovery after intense chemotherapy were employed for autologous hematological reconstitution after very-high-dose chemotherapy (CVB combination). At the time of graft 2 patients were in 1st remission and 2 in 2nd, while the remaining 4 had persistence or progression of disease. Autografted patients received 3.4 +/- 8.3 (mean 5.2) x 10e8/Kg mononuclear cells and 2.1 +/- 40.5 (mean 22.5) x 10e4/Kg CFU-GM. All patients had prompt and sustained engraftment, though in one case platelets never reached normal levels. Recovery time was respectively 10 +/- 17 days (mean 13.2) for granulocytes 0.5 x 10e9/L, and 10 +/- 49 days (mean 20.3) for platelets greater than 50.0 x 10e9/L, with an interval of less than 4 days from greater than 0.5 to greater than 1.0 granulocytes in 7 out of the 8 patients. All patients are currently alive at 57 +/- 645 (median 262) days, and 7 in remission at 61 +/- 645 (median 297) days from autologous blood stem cell transplantation (ABSCT). Our study demonstrates that CSC collected after mobilizing chemotherapy are able to promptly restore and sustain hemopoiesis after marrow ablative chemotherapy in patients with malignant lymphoma. CSC reduce toxicity and hospitalization so impressive, that in malignant lymphomas ABSCT could rapidly be considered for first line strategy.

Adult↗
PubMedDate not supplied

Collection of PBSC with Fenwal CS-3000 for autografting.

The peripheral blood represents an alternative source of haemopoietic progenitors and permits autografting in patients who have contraindications for a bone marrow harvest but who are otherwise candidates for autologous bone marrow transplantation. Circulating stem cells can be harvested performing several leucaphereses during the overshoot after a mobilization chemotherapy. The use of Fenwal CS-3000 cell separator allows reproducibility from donor to donor and makes the procedure very efficient. We collected peripheral blood stem cells (PBSC) in four patients, 2 with Hodgkin's lymphoma, 1 with high-grade non-Hodgkin's lymphoma and 1 with secondary FAB unclassifiable ANLL: the procedures of collection and cell harvests obtained are reported.

Adult↗
PubMedDate not supplied

Circulating stem cell autograft in malignant lymphomas.

Autologous peripheral blood stem cells (PBSC) collected after an intensive course of chemotherapy were employed for hematological reconstitution in 3 patients (age 24-44 years), 2 with Hodgkin's and 1 with high-grade non-Hodgkin's lymphoma, in 2nd complete or partial remission. PBSC collections were performed with a Fenwal CS-3000 cell separator (programs "3" and "1-modified"). After collection and partial RBC removal, cells were cryopreserved and stocked in liquid nitrogen. In all patients the CVB combination was employed as myeloablative transplant regimen. Patients received respectively 28.0, 33.1 and 12.3 x 10(4)/Kg peripheral blood CFU.GM. Hematologic recovery was prompt and complete in 2 patients, while a patient with Hodgkin's lymphoma who had previously been treated with combined modality, is still moderately thrombocytopenic and granulocytopenic 148 days post graft. Patients are currently alive and disease-free 148-301 days post graft.

Adult↗
PubMedDate not supplied

Wernicke-like encephalopathy after autologous bone marrow transplantation.

A 15-year-old boy with non-T ALL in early 2nd remission was autografted using a regimen with busulphan 4 mg/kg/day, po, from day -9 to -6, and cyclophosphamide 50 mg/kg/day, iv, from day -5 to -2. During busulphan administration he experienced a few generalized seizures, and starting on day 25 post ABMT he developed a progressively severe neurological symptomatology characterized by nystagmus, right VIth cranial nerve palsy, truncal ataxia and, finally, confusion and coma. MRI showed lesions in the periaqueductal gray matter, thalamus, mammillary bodies and putamen. Within 24 hours of treatment with thiamine he improved dramatically, but during the following weeks permanent neurologic damage with memory deficit, truncal ataxia and nystagmus became evident. To our knowledge this is the first case of Wernicke's encephalopathy reported after BMT. We suspect in this case a contribution of busulphan to the development of the syndrome.

Adolescent↗