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M Rovira

Publications and source records attributed to M Rovira.

At least 55 records · Page 3Linked to original sources

Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation.

Delayed immune reconstitution following allogeneic stem cell transplantation remains a major clinical problem, resulting in significant transplant-related mortality from infectious complications. The recovery of immunity after bone marrow transplantation (BMT) is a complex process dependent on a large number of pre- and post-transplant factors. It has been suggested that the use of peripheral blood instead of bone marrow as stem cell source may accelerate immune reconstitution after allogeneic transplantation. Some authors have recently reported a more rapid recovery of the number and function of T and B cells after allogeneic peripheral blood progenitor cell transplant (allo-PBPCT) in comparison with conventional BMT, results which would reflect the high number of lymphocytes infused to the patients. Such a rapid immune recovery could indeed contribute to the apparent therapeutic advantage of PBPCT when compared with BMT. However, there is limited knowledge on this issue and randomized trials are required to prove whether allo-PBPCT is indeed superior to BMT in terms of immune reconstitution post-transplant. A review of some quantitative and functional aspects of immune recovery after allo-PBPCT is presented in this article.

Adolescent↗

[The autologous transplantation of hematopoietic precursors on an outpatient basis: an analysis of its feasibility at the Hospital Clínic de Barcelona].

BACKGROUND: Autologous stem cell transplantation (ASCT) is increasingly performed on an outpatient basis. Preliminary results show a significant financial saving without modifying the therapeutic results. The aim of this study has been to evaluate the feasibility of this procedure in our the Hospital Clínic of Barcelona, Spain. PATIENTS AND METHODS: All patients in whom an ASCT due to a hematological malignancy, having a good performance status, a caregiver 24 h per day, a lodging near to the hospital and an appropriate cultural and social environment, were offered an outpatient management starting the day after stem cell administration (day +1). RESULTS: During the study period (April, 1997-June, 1998) 64 ASCT were performed. Fifteen patients (23%) were managed on an outpatient basis. The remaining patients were not included in the study due to patient preference (26%), medical reasons (22%), distant home (18%) and social problems (9%). Seven patients (47%) had to be readmitted in the hospital due to fever (n = 4), nausea (n = 2) or respiratory distress (n = 1). Patients receiving total body radiation (TBI) in the conditioning regimen did not have a higher readmission rate than those conditioned without TBI. The median hospital stay (since day +1) was 6 (range: 0-22) and 17 (13-117) days for outpatient and inpatients respectively (p = 0.0016). This reduction would imply a saving of 65% in hospitalization charges and of 12% in total charges. All patients having elected the outpatient management were very satisfied by having made that choice. CONCLUSION: With an appropriate patient selection, outpatient ASCT is a feasible method that may improve the quality of life of the patients and can reduce the costs of the procedure.

Adolescent↗

Immune reconstitution following allogeneic peripheral blood progenitor cell transplantation: comparison of recipients of positive CD34+ selected grafts with recipients of unmanipulated grafts.

We compared the kinetic recovery of lymphocytes and their subsets in two groups of patients submitted to allogeneic peripheral blood progenitor cell transplantation (allo-PBT): those receiving lymphocyte-depleted leukaphereses by positive selection of CD34+ cells (group 1, n = 18) and those receiving unmanipulated leukaphereses (group 2, n = 15). Patients were conditioned with cyclophosphamide (120 mg/kg) and fractioned total body irradiation (13 Gy, group 1; 12 Gy, group 2). The mean number (x 10(6)/kg) of CD34+ and CD3+ cells infused was 4.0 and 0.67, respectively, in group 1 patients, and 4.7 and 274, respectively, for group 2 patients. Graft-versus-host disease prophylaxis consisted of cyclosporin A + methylprednisolone for group 1 and cyclosporin A + methotrexate for group 2. Median follow-up was 7 months (range 2-8 months) for both groups. During the first 6 months post-transplant, CD4+ cell counts were lower in group 1 as compared with group 2 (p = 0.014, 0.010, 0.011, 0.0003, and 0.052 at 0.5, 1, 2, 3, and 6 months, respectively), whereas there was no difference at 8 months. The number of CD4+CD45RA+ cells was very low throughout the study in both groups, being lower in group 1 than in group 2, especially during the first 3 months post-transplant (p = 0.007 and 0.0006 at 1 and 3 months). Normal levels of CD8+ cells were reached by 1 month post-transplant in both groups. TCR gamma delta + cell counts were lower in group 1 than in group 2 during the first 4 months post-transplant (p = 0.001, 0.004, and 0.04 at 1, 3, and 4 months). A normal number of natural killer cells (CD3-CD56+) was achieved 1 month post-transplant in both groups. B lymphocytes (CD19+) showed low or undetectable counts throughout the first 4 months in both groups, achieving the normal range at 8 months. These results show that, during the first 6 months following allo-PBT with CD34+ selected grafts, the number of CD4+, CD4+CD45RA+, and TCR gamma delta + cells is significantly lower than after unmanipulated allo-PBT; these differences disappeared at 8 months. In contrast, there are no differences between transplant groups in the recovery of CD8+, CD19+, and natural killer cells.

Adolescent↗

Effects of short-term administration of G-CSF (filgrastim) on bone marrow progenitor cells: analysis of serial marrow samples from normal donors.

To determine the effect of G-CSF administration on both the total number of CD34+ cells and the primitive CD34+ subsets in bone marrow (BM), we have analyzed BM samples serially obtained from 10 normal donors in steady-state and during G-CSF treatment. Filgrastim was administered subcutaneously at a dosage of 10 microg/kg/day (n = 7) or 10 microg/kg/12 h (n = 3) for 4 consecutive days. Peripheral blood sampling and BM aspirates were performed on day 1 (just before G-CSF administration), day 3 (after 2 days of G-CSF), and day 5 (after 4 days of G-CSF). During G-CSF administration, a significant increase in the total number of BM nucleated cells was observed. The percentage (range) of CD34+ cells decreased in BM from a median of 0.88 (0.47-1.44) on day 1 to 0.57 (0.32-1.87), and to 0.42 (0.16-0.87) on days 3 and 5, respectively. We observed a slight increase in the total number of BM CD34+ cells on day 3 (0.66 x 10(9)/l (0.13-0.77)), and a decrease on day 5 (0.23 x 10(9)/l (0.06-1.23)) as compared with steady-state (0.40 x 10(9)/l (0.06-1.68)). The proportion of primitive BM hematopoietic progenitor cells (CD34+CD38-, CD34+HLA-DR-, CD34+CD117-) decreased during G-CSF administration. In parallel, a significant increase in the total number of CD34+ cells in peripheral blood was observed, achieving the maximum value on day 5. These results suggest that in normal subjects the administration of G-CSF for 5 days may reduce the number of progenitor cells in BM, particularly the most primitive ones.

Adult↗

Central venous catheter exchange by guidewire for treatment of catheter-related bacteraemia in patients undergoing BMT or intensive chemotherapy.

Current guidelines for the treatment of catheter-related bacteraemia (CRB) advise against central venous catheter (CVC) exchange because of the potential risk of prolonging infection. However, there are no consistent data proving this recommendation. We evaluated prospectively the usefulness of CVC exchange by guidewire for the treatment of CRB in patients undergoing BMT or intensive chemotherapy. CVC exchange was considered when fever and positive blood cultures persisted after 2 days of adequate antimicrobial therapy and no potential source of bacteraemia other than CVC could be identified. The guidewire exchange was preceded and followed by a slow infusion of adequate antimicrobial therapy. Bacteraemia was confirmed as catheter-related by demonstrating concordance between isolates from the tip and blood cultures by pulsed-field electrophoresis of genomic DNA. This procedure was performed in 19 episodes of bacteraemia during a 1-year period. Fourteen episodes (74%) were catheter-related and 71% of these were due to coagulase-negative staphylococci. Guidewire replacement was accomplished uneventfully 4 days after development of sepsis (range 3-6). In all cases, clinical signs of sepsis disappeared in less than 24 h after replacement. Definitive catheter withdrawal was carried out a median of 16 days (range 3-42) after guidewire exchange; in all cases, the tip culture was negative. We conclude that CVC replacement by guidewire under adequate antimicrobial therapy may be a reasonable option for the treatment of CRB when antimicrobial therapy alone has been unsuccessful.

Adult↗

Efficacy and toxicity of a high-dose G-CSF schedule for peripheral blood progenitor cell mobilization in healthy donors.

An important issue in allogeneic peripheral blood progenitor cell transplantation is the optimization of the regimen of mobilization of progenitor cells from normal donors. It has been shown that for G-CSF doses up to 10 microg/kg/day, a dose-response relationship exists for the degree of progenitor cell mobilization. Formal comparisons with doses higher than 10 microg/kg/day, however, have not been reported. The aim of this study was to compare the mobilization and collection results of two different G-CSF (Filgrastim) schedules: 10 microg/kg/12 h (n = 20; group A) vs 10 microg/kg/24 h (n = 20; group B). Apheresis sessions were started on day 5 (after 4 days of G-CSF). Adverse events consisted of bone pain, headache, and fatigue which required treatment with acetaminophen +/- codeine in both donor groups. Discontinuation of G-CSF administration for intolerable side-effects was not necessary in any case. The increase in peripheral leukocyte and lymphocyte counts x 109/l on day 5 was higher in group A (56.2 (37.1-75.2) and 4.4 (2. 1-14.6), respectively) than in group B (27.5 (13.2-53.9) and 2.6 (1. 9-5.1), respectively) (P < 0.0001 and P = 0.008). Platelets x 109/l decreased in group A from 228 (161-286) before G-CSF administration to 207 (155-328) on day 5 (P = 0.03), whereas no change was observed in group B. Following the first apheresis, a significant decrease in platelet count was observed with both G-CSF schedules without any differences between groups. The number x 106/kg of both nucleated and CD34+ cells collected after the first apheresis session was higher in group A (672 (462-992) and 5.9 (3.4-10.4), respectively) than in group B (427 (319-608) and 3.1 (1.1-6.8), respectively) (P = 0.0003 in both cases). The median number of CD3+cells x 106/kg collected after one apheresis session was similar with both G-CSF schedules (212 (91-430) in group A and 170 (110-291) in group B) (P = NS). In conclusion, the schedule of 10 microg/kg/12 h was well tolerated and resulted in the collection of a higher number of progenitor cells than 10 microg/kg/24 h without increasing the T cell content. This approach could avoid the donor having to undergo a second apheresis, and facilitate further graft manipulation.

Adult↗

Lumbar extradural hemangiomas: report of three cases.

The CT, MR, and histologic findings of three patients with surgically proved lumbar extradural cavernous and arteriovenous hemangiomas are reported. All three patients suffered from radicular and low back pain that disappeared completely or nearly so after total surgical excision. In each case, neuroimaging studies showed a well-defined ventrally located extradural mass with no bone involvement. On MR images, all lesions were homogeneous and isointense on noncontrast T1-weighted images and hyperintense on T2-weighted images relative to the intervertebral disk. Homogeneous enhancement was seen in one of the two cases in which contrast-enhanced T1-weighted images were obtained. Purely extradural hemangiomas should be included in the differential diagnosis of lumbar extradural soft-tissue lesions. Features that may help to distinguish this entity from the more common extruded disk herniation or neurogenic tumors are its homogeneous high signal intensity on T2-weighted images, ovoid shape, and lack of anatomic relationship with the adjacent intervertebral disk or exiting nerve root.

Adolescent↗

Hematopoietic stem cell transplantation in chronic lymphocytic leukemia: a report of 12 patients from a single institution.

BACKGROUND: Stem-cell transplantation is a reasonable therapeutic approach for younger patients with high-risk CLL. PATIENTS AND METHODS: Twelve patients (seven males; median age 47 years, range 29-51) with high-risk CLL underwent transplantation (allo, n = 7; auto, n = 5). The conditioning regimen consisted of cyclophosphamide and total body irradiation in 11 patients, and BEAC in the remaining one. Minimal residual disease (MRD) was assessed by cytofluorometry and PCR. RESULTS: All 11 evaluable patients engrafted. Of the seven allografted patients, two died of treatment-related causes; three patients developed acute GVHD. No transplant-related mortality was observed in autografted patients. After transplantation, 10 of 11 patients evaluable for response achieved CR (91%; 95% CI 59%-100%) which was molecular in nine patients (82%; 95% CI 48%-98%). One patient in CR but MRD+ relapsed nine months after transplantation and died. Seven patients remain in molecular CR for a median of 16 months (range 1-58). Estimated actuarial survival and disease-free survival at two years is 81% (95% CI 43%-100%) and 71% (95% CI 43%-99%), respectively. Relapse risk at two years is 12.5% (95% CI 0%-35.5%). CONCLUSIONS: Patients with high-risk CLL can achieve long-lasting molecular CR after SCT. The role of transplants in CLL management deserves investigation in controlled trials.

Adult↗

Demonstration of donor origin of CD34+ HLA-DR- bone marrow cells after allogeneic peripheral blood transplantation with a long follow-up.

Peripheral blood progenitor cells (PBPC) are increasingly being used to perform allogeneic transplants (allo-PBPCT). An important issue regarding allo-PBPCT is the potential for long-term engraftment of human PBPC. A subset of bone marrow (BM) cells displaying the immunophenotype CD34+ HLA-DR- has functional properties associated with pluripotential stem cells. We studied the origin (donor vs recipient) of CD34+ HLA-DR- hematopoietic cells from patients having received allo-PBPCT and with a long follow-up (14+ to 21+ months). Chimeric status was determined after amplification by polymerase chain reaction (PCR) of short tandem repeat sequences (PCR-STR). Four patients (acute myeloid leukemia (n = 3), acute lymphoid leukemia (n = 1) were studied. CD34+ HLA-DR- cells from bone marrow aspirates were isolated by flow cytometry cell sorting. The mean percentage of CD34+ cells among the total nucleated BM cells from the four patients was 0.6+/-0.2% (mean +/- s.d.) (range, 0.31-1.27%). The CD34+ HLA-DR- cells accounted for 1.54+/-0.54 (range, 0.9-2.05%) of the CD34+ BM cells. The purity of the CD34+ HLA-DR- cells analyzed after sorting was higher than 94% in all sorted fractions. PCR-STR of these cells showed donor origin in all patients. The origin of CD34+ HLA-DR- bone marrow cells in patients treated with allo-PBPCT has not so far been analyzed. These results provide further evidence that G-CSF-mobilized PBPC contains cells which are capable of sustained long-term engraftment.

Adult↗

Use of intravenous immune globulin in addition to antiviral therapy in the treatment of CMV gastrointestinal disease in allogeneic bone marrow transplant patients: a report from the European Group for Blood and Marrow Transplantation (EBMT). Infectious Diseases Working Party of the EBMT.

The best treatment of CMV gastrointestinal disease has been controversial, with some centers adding intravenous (i.v.) Ig to antiviral chemotherapy. The aim of this retrospective survey was to compare the outcome of antiviral chemotherapy with or without i.v. Ig. A questionnaire was sent to centers belonging to the EBMT. Thirty-three patients with CMV gastrointestinal disease were reported, 22 patients were given antiviral chemotherapy alone and 11 patients a combination of antiviral chemotherapy and i.v. Ig. Eighteen of 33 (55%) patients responded to therapy, 13 of those treated with antiviral chemotherapy alone and five (45%) of those treated with the combination (P = NS). Patients with acute GVHD of grades II-IV had significantly worse outcomes than patients with acute GVHD grades 0-I. In a Cox proportional hazards model corrected for acute GVHD there was no difference in outcome of CMV gastrointestinal disease with or without addition of Ig. Survival at 100 days after diagnosis of CMV gastrointestinal disease was 64%. There was no difference in survival in patients treated with or without i.v. Ig. The results of this retrospective survey indicate that addition of i.v. Ig to antiviral chemotherapy might not improve outcome in patients with biopsy-proven CMV gastrointestinal disease.

Adolescent↗

Pulmonary complications in patients with haematological malignancies treated at a respiratory ICU.

Patients with haematological malignancies developing severe pulmonary complications have a poor outcome, especially after bone-marrow transplantation (BMT). We studied the aetiology, the yield of different diagnostic tools, as well as the outcome and prognostic factors in the corresponding population admitted to our respiratory intensive care unit (RICU). Overall, 89 patients with haematological malignancies and pulmonary complications treated within a 10 yr period were included. The underlying malignancies were predominantly acute leukaemia and chronic myeloid leukaemia (66/89, 74%). Fifty-two of 89 (58%) patients were bone marrow recipients. An aetiological diagnosis could be obtained in 61/89 (69%) of cases. The aetiology was infectious in 37/89 (42%) and noninfectious in 24/89 (27%). Blood cultures and cytological examinations of bronchoalveolar lavage fluid were the diagnostic tools with the highest yield (13/43 (30%) and 13/45 (29%) positive results, respectively). Necropsy results were coincident with results obtained during the lifetime in 43% of cases with infectious and 60% with noninfectious aetiologies. Overall mortality was 70/89 (79%), and 47/52 (90%) in transplant recipients. The requirement of mechanical ventilation, BMT, and an interval <90 days of BMT prior to ICU admission were independent adverse prognostic factors. The outcome in this patient population was uniformly poor. It was worst in bone marrow recipients developing pulmonary complications <90 days after transplantation and requiring mechanical ventilation. Decisions about intensive care unit admission and mech-anical ventilation should seriously consider the dismal prognosis of these patients.

Adolescent↗

[Second allogeneic progenitor cell transplantation for leukemia relapse: results in 10 patients].

BACKGROUND: Leukemia relapse is an important cause of treatment failure after allogeneic progenitor cells transplantation. A minority of patients achieve a long-term disease free survival with a second transplant, but the majority die of toxicity or relapse. We report our experience with second allogeneic transplant for leukemia relapse. PATIENTS AND METHODS: Ten patients were treated with a second transplant. Their diagnosis were chronic myelogenous leukemia (n = 5) and acute leukemia (n = 5). The interval between transplants ranged from 4 to 59 months (median 26 months). Conditioning regimens were busulfan alone (n = 1), associated to cyclophosphamide (n = 6) or to cyclophosphamide plus etoposide (n = 3). Acute graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin (CSA) (n = 4), CSA plus methotrexate (n = 4), CSA plus prednisolone (n = 1), or CSA, methotrexate plus partial T cell depletion (n = 1). RESULTS: All patients engrafted after second transplant. Seven developed acute GVHD. Four out of the nine patients at risk (44%) developed chronic GVHD. Three had clinical criteria of hepatic veno-occlusive disease. Three patients died in complete remission due to treatment-related toxicity: pulmonary invasive aspergillosis during an acute GVHD, interstitial pneumonitis plus chronic GVHD, and, hepatic veno-occlusive disease, respectively. Two patients relapsed 4 and 5 months after second transplant. Five remained alive in complete remission after a median follow-up of 27 months. In all of them acute or chronic GVHD incidence and severity after second transplant was higher than after the first transplant. All surviving patients were transplanted more than 12 months after the first transplant. CONCLUSIONS: A proportion of patients that relapse after an allogeneic progenitor cells transplant may benefit from second transplant; especially, young patients having a good performance status, and with a long interval between transplants.

Adult↗

Rapid engraftment without significant graft-versus-host disease after allogeneic transplantation of CD34+ selected cells from peripheral blood.

We have prospectively evaluated the feasibility and results of the biotin-avidin immunoadsorption method (Ceprate SC system) for a phase I/II study of T-cell depletion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood progenitor cells (PBPC) for allogeneic transplantation. Twenty consecutive patients, median age, 40 years (21 to 54) and diagnoses of chronic myeloid leukemia in chronic phase (n = 5), acute myeloblastic leukemia (n = 7), acute lymphoblastic leukemia (n = 2), chronic myelomonocytic leukemia (n = 1), refractory anemia with excess of blasts in transformation (n = 3), histiocytosis X (n = 1), and chronic lymphocytic leukemia (n = 1), were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (13 Gy; 4 fractions). HLA identical sibling donors received G-CSF at 10 microg/kg/d subcutaneously (SC); on days 5 and 6 (19 cases) and days 5 to 8 (1 case) donors underwent 10 L leukapheresis. PBPC were purified by positive selection of CD34+ cells using immunoadsorption biotin-avidin method (Ceprate SC) and were infused in the patients as the sole source of progenitor cells. No growth factors were administered posttransplant. The median recovery of CD34+ cells after the procedure was of 65%. The median number of CD34+ cells infused in the patients was 2.9 (range, 1.5 to 8.6) x 10(6)/kg. The median number of CD3+ cells administered was 0.42 x 10(6)/kg (range, 0.1 to 2). All patients engrafted. Neutrophil counts >500 and >1,000/microL were achieved at a median of 14 days (range, 10 to 18) and 15 days (range, 11 to 27), respectively. Likewise, platelet counts >20,000 and >50,000/microL were observed at a median of 10 days (range, 6 to 23) and 17 days (range, 12 to 130), respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine plus methylprednisolone. No patient developed either grade II to IV acute or extensive chronic GVHD. After a median follow-up of 7.5 months (range, 2 to 22) three patients have relapsed, and one of them is again in hematologic and cytogenetic remission after infusion of the donor lymphocytes. Two patients died in remission: one on day +109 of pulmonary aspergillosis and the other on day +251 of metastasic relapse of a previous breast cancer. Sixteen of the 20 patients are alive in remission after a median follow-up of 7.5 months (range, 2 to 22). In conclusion, despite the small number of patients and limited follow-up, it appears that this method allows a high CD34+ cell recovery from G-CSF mobilized PBPC and is associated with rapid engraftment without significant GVHD, and with low transplant related mortality.

Adolescent↗

[Hemopoietic progenitor cell transplantation: 20 years' experience at the Hematology School "Farreras-Valentí"/Clinical Hospital of Barcelona].

BACKGROUND: Hemopoietic progenitor cell transplantation (HPCT) is acquiring an increasing role in the therapy for a variety of disorders. In this study, main characteristics and results of HPCT along 20 years are analyzed from the experience of Postgraduate School of Hematology "Farreras-Valentí" at the Hospital Clínic in Barcelona. PATIENTS AND METHODS: Six-hundred ninety-five patients transplanted between June 1976 and January 1996 were analyzed. Median age (range) were 33 (4-63) years. The following aspects were considered: donor type, source or progenitor cells, type of disease and disease-stage at transplantation, transplant related mortality and survival. RESULTS: A total of 714 HPCT were performed (448 allogeneic, 13 isogeneic, 253 autogeneic). Allogeneic HPCT were from an HLA-identical sibling in 408 cases, from other familial donors in 10, and from non-familial donors in 30. Most HPCT from non-familial donors (93%) were performed during the last five years of the study (1991-1995). The source of hemopoietic progenitor cells was bone marrow in 625 instances (88%), peripheral blood in 88 (12%), and fetal liver in one. During more than 15 years, the only source of progenitors was the bone marrow; in contrast, in the last 3 years (1993-1995) transplants using peripheral blood were predominant. Main indications for HPCT were the following: acute leukemias (n = 387) (54%), chronic leukemias (n = 134) (19%), severe aplastic anemia (n = 58) (8%), lymphomas (n = 80) (11%), multiple myeloma (n = 39) (5%) and myelodysplastic syndromes (n = 14) (2%). In patients with hematological malignancies (n = 656), HPCT was performed in first complete remission or in first chronic phase in 321 instances (49%), in subsequent remissions in 144 (22%), and in more advanced stages in the remaining 191 (29%). In the more recent years, a progressive decrease in the number of HPCT for acute leukemia or aplastic anemia was observed, contrasting with an increase in transplants for lymphoma, multiple myeloma and myelodysplastic syndromes. Of note, a significant decrease in transplant related mortality was evident along the years, both after autogeneic HPCT (21% during 1985-1992 and 6% thereafter) (p = 0.001) and after allogeneic transplantation (54%, 44%, and 20% during the periods 1976-1984, 1985-1992 and 1993-1995, respectively) (p = 0.004). The fact translated into an increase in the actuarial probability of survival after allogeneic HPCT (25%, 33% and 58% in the three mentioned periods, respectively) (p = 0.0003), and after autogeneic HPCT (33% in the interim 1985-1992, and 55% in the period 1993-1995) (p = 0.001). CONCLUSIONS: During the last 20 years, HPCT has significantly evolved in aspects such as type of donor, source of progenitor cells and indications. Remarkably, a progressive decrease in transplant related mortality has been observed translating into a improvement in survival after the procedure.

Actuarial Analysis↗

Successful autografting in chronic myelogenous leukaemia using Philadelphia negative blood progenitor cells mobilized with rHuG-CSF alone in a patient responding to alpha-interferon.

Several non-randomized studies suggest a possible survival advantage for chronic myelogenous leukaemia (CML) patients treated with an autologous stem-cell transplantation. Due to the possible contribution of residual leukaemic cells present in the inoculum in post-transplant relapse, several methods are being evaluated to eliminate neoplastic cells or to select 'normal' (Ph1 negative) progenitor cells for autografting. Recently, several studies have shown that Ph1 negative blood progenitor cells can be mobilized by rHuG-CSF alone in patients who have a cytogenetic response to alpha-interferon (IFN). We describe the first case, as far as we are aware, of a CML patient responding to IFN autografted by using blood progenitor cells collected by rHuG-CSF alone.

Adolescent↗

[Allogeneic transplant of peripheral blood hematopoietic progenitors. Preliminary experience].

Myeloablative treatment followed by allogeneic transplantation of peripheral blood hemopoietic progenitors (alloPBT) was administered to five leukemia patients with a high risk of relapse. The donors subcutaneously received 10 micrograms/kg/day of G-CSF for five days. The tolerance to this medication was good with only complaints of moderate bone pain. Two of the peripheral blood donors had previously been bone marrow donors and both expressed their preference for the new method. The product of peripheral blood leukapheresis contained from one to four-fold more hemopoietic progenitors and approximately ten-fold more T-lymphocytes than the bone marrow received from normal donors. Prophylaxis of the graft versus host disease (GVHD) consisted of cyclosporine A (CsA) in one case and CsA and methotrexate (MTX) in four cases. The bone marrow implantation was verified with a neutrophil count of up to more than 0.5 x 10(9)/l between days 12 to 21 after transplant and a platelet count higher than 20 x 10(9)/l from days 11 to 41 after transplant. Acute GVHD was clinical grade O (two cases), II (one case) and grade III (two cases). In conclusion, alloPBT may be more safely and comfortably performed to the donor. This method may provide rapid recovery of neutrophils and platelets in patients without an apparent increase in the risk of developing graft versus host disease.

Adolescent↗

Study of hematopoietic chimerism following allogeneic peripheral blood stem cell transplantation using PCR amplification of short tandem repeats.

Allogeneic peripheral blood progenitor cell transplantation (PBPCT) is increasingly being used to treat hematologic malignancies. However, the capacity of PBPC to maintain long-term hematopoiesis remains controversial. To add further information to this issue we studied the chimeric status in 12 patients receiving G-CSF-mobilized PBPC from HLA-identical sibling donors. All patients were conditioned with cyclophosphamide and total body irradiation. In six cases the apheresis product was partially T-cell depleted by counterflow centrifugation (n = 2) or the immunoadsorption biotin-avidin method (n = 4). The follow-up was longer than 6 months in five patients, with a maximum of 420 days. Molecular analysis of the engraftment was done using PCR amplification of short tandem repeats. Apparent complete donor chimerism was detected in all patients between 28 and 420 days after engraftment. This study indicates that full short-term engraftment is achieved in patients receiving allogeneic G-CSF-mobilized PBPC from healthy donors and suggests that this might also be true for long-term engraftment.

Adult↗

Effects of G-CSF administration and peripheral blood progenitor cell collection in 20 healthy donors.

The effects of both daily G-CSF administration and subsequent peripheral blood progenitor cell collection (PBPCC) by apheresis on 20 healthy adult donors were studied. All received daily G-CSF (filgrastim) 10 micrograms/kg for 5-7 days by subcutaneous injection. G-CSF administration was well tolerated, except for moderate bone pain and headache. Peak values of CD34+ cells were observed on days 5 (n = 12) or 6 (n = 8). In all donors a significant increase in CD3+, CD4+, CD8+, CD19+, and NK cells was observed on day 5 in relation to the baseline values. CD4/CD8 lymphocyte ratio was unmodified by G-CSF. None of the donors required a central venous line for PBPCC. Immediately after PBPCC, a platelet count below 100 x 10(9)/1 was observed in nine of 18 cases, although in all donors platelet counts were over 100 x 10(9)/1 7 days later. A lymphocytopenia on day 7 following PBPCC was observed, although there was a tendency to achieve baseline values 30-90 days after the procedure. Mean numbers ( +/- SD) of collected cells x 10(6)/kg after a median of two (1-4) apheresis sessions and a median of 20 1 (10-40) processed were: CD34+ 5.5 ( +/- 2.3), CD3+ 326 ( +/- 105), CD4+ 207 ( +/- 64), CD8+ 164 ( +/- 60), CD19+ 88 ( +/- 32), and NK cells 32 ( +/- 14). We conclude that G-CSF administration to healthy donors is a well-tolerated procedure which is associated with (a) obtaining a high number of hematopoietic progenitor cells, and (b) a significant increase in T, B, and NK cells in donors' blood. In addition, PBPCC by apheresis results in a moderate, rapidly reversible, and clinically irrelevant thrombocytopenia and a moderate lymphocytopenia, which tends to resolve within 3 months following the procedure.

Adolescent↗