-
E Jantunen, C Canals,
M Attal,
K Thomson,
N Milpied,
A Buzyn,
A Ferrant,
P Biron,
C Crawley,
A Schattenberg,
J J Luan,
H Tilly,
B Rio,
P W Wijermans,
P Dreger,
A Sureda
[show abstract]
[hide abstract]
ABSTRACT: Limited experience is available on the feasibility and efficacy of autologous stem-cell transplantation (ASCT) in patients with mantle cell lymphoma (MCL) beyond 65 years.
We analysed 712 patients with MCL treated with ASCT from 2000 to 2007 and reported to the European Group for Blood and Marrow Transplantation registry. Patients>65 years were compared with patients<65 years for the end points non-relapse mortality (NRM), relapse incidence, progression-free survival (PFS), and overall survival (OS).
Seventy-nine patients were ≥65 years old. Median time from diagnosis to ASCT was longer in the elderly patients (11 versus 9 months, P=0.005); they had more commonly received at least two treatment lines (62.0% versus 47.9%, P=0.02) and were less commonly in first complete remission at ASCT (35.4% versus 51.2%, P=0.002). Median follow-up after ASCT was 19 and 25 months, respectively. NRM was comparable at 3 months (3.8% versus 2.5%) and at 5 years (5.6% versus 5.0%). There were no differences in relapse rate (66% versus 55% at 5 years), PFS (29% versus 40%) and OS (61% versus 67%) between both populations of patients.
ASCT beyond 65 years of age is feasible in selected patients with MCL and results in similar disease control and survival as in younger patients.
Annals of Oncology 04/2011; 23(1):166-71. · 6.43 Impact Factor
-
Bone marrow transplantation 03/2011; 47(2):296-8. · 3.00 Impact Factor
-
J Delgado, C Canals,
M Attal,
K Thomson,
A Campos,
R Martino,
T Littlewood,
G Jackson,
N Milpied,
M Boogaerts,
A Hunter,
J J W M Janssen,
S Montoto,
A Sureda
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 12/2010; 25(3):551-5. · 8.30 Impact Factor
-
Ch. Kyriakou, C. Canals,
D. Sibon,
J. Yves Cahn,
M. Kazmi,
W. Arcese,
K. Kolbe,
N. Claude Gorin,
K. Thomson,
N. Milpied,
D. Niederwieser,
K. Indrák,
P. Corradini,
A. Sureda,
N. Schmitz
International Journal of Clinical Oncology 01/2010; · 1.41 Impact Factor
-
Annals of Hematology 08/2008; 87(7):599-600. · 2.62 Impact Factor
-
S Montoto, C Canals,
A Z S Rohatiner,
G Taghipour,
A Sureda,
N Schmitz,
C Gisselbrecht,
L Fouillard,
N Milpied,
C Haioun,
S Slavin,
E Conde,
C Fruchart,
A Ferrant,
V Leblond,
H Tilly,
T A Lister,
A H Goldstone
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the outcome of a large series of patients who received high-dose treatment (HDT) for follicular lymphoma (FL), 693 patients undergoing HDT (total-body irradiation (TBI)-containing regimen: 58%; autologous bone marrow (BM)/peripheral blood progenitor cells (PBPCs): 378/285 patients) were included in the study. A total of 375 patients (54%) developed recurrent lymphoma, 10-year progression-free survival (PFS) being 31%. On multivariate analysis, younger age (P=0.003) and HDT in first complete remission (CR1) (P<0.001) correlated with longer PFS. With a median follow-up of 10.3 years, 330 patients died. Ten-year overall survival (OS) from HDT was 52%. Shorter OS was associated on multivariate analysis with older age (P<0.001), chemoresistant disease (P<0.001), BM+PBPC as source of stem cells (P=0.007) and TBI-containing regimens (P=0.004). Thirty-nine patients developed secondary myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML), in 34 cases having received TBI as the conditioning regimen. The 5-year non-relapse mortality (NRM) was 9%. On multivariate analysis, older age (P<0.001), refractory disease (P<0.001) and TBI (P=0.04) were associated with a higher NRM. This long follow-up study shows a plateau in the PFS curve, suggesting that a selected group of patients might be cured with HDT. On the downside, TBI-containing regimens are associated with a negative impact on survival.
Leukemia 12/2007; 21(11):2324-31. · 9.56 Impact Factor
-
D Valcárcel,
R Martino,
A Sureda, C Canals,
A Altés,
J Briones,
M A Sanz,
R Parody,
M Constans,
S L Villela,
S Brunet,
J Sierra
[show abstract]
[hide abstract]
ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA)-compatible sibling donors is a potential curative treatment for hematological and non-hematological malignancies. Nevertheless, high mortality rates may be associated with this therapy, especially in older patients, those with other comorbidities or who receive a second HSCT.
We analyzed the factors associated with transplant-related mortality (TRM) and overall survival in 157 consecutive adult patients (104 males and 53 females) who received a HSCT [29 bone marrow (BM) transplantation and 128 peripheral blood (PB) transplantation] from a HLA-identical sibling between January 1995 and March 2002 in our institution. One hundred patients received a standard conditioning prior to HSCT (STAND) and 57 patients received a reduced-intensity conditioning (RIC) HSCT. Fifty-eight patients were in an early phase at transplant and 99 in a non-early phase. Median age was 46 yr (16-66), and 90 patients (57%) were >45 yr of age.
Patients in the RIC group were older than those in the STAND group, and had a higher proportion of non-early disease phases including a prior autologous HSCT in 39%. Median follow-up for survivors was 28 and 15 months in the STAND and RIC groups (P < 0,001), respectively. Cumulative incidence of TRM at 2 yr was 30% [95% confidence interval (CI) 22-41%] for the STAND group and 22% (95% CI 13-37%) for the RIC group [non-significant (NS)]. Factors associated with a higher TRM in multivariate analysis were: STAND vs. RIC conditioning regimen [relative risk (RR) 5.4; 95% CI 2.3-12.8; P < 0.001]; age > or =45 yr vs. <45 yr (RR 5; 95% CI 2.4-10.8, P < 0.001); second vs. first HSCT (RR 2.8, 95% CI 1.3-6.3, P = 0.01) and non-T-cell-depleted vs. T-cell-depleted graft (RR 2.7, 95% CI 1.3-5.8, P = 0.009). Overall survival (OS) at 2 yr was 52.5 +/- 10.4% for STAND group and 59 +/- 16.8% in RIC group. Factors associated with poorer OS in multivariate analysis were: STAND vs. RIC conditioning regimen (RR 3.4, 95% CI 1.7-6.9, P = 0.001); age > or =45 vs <45 yr (RR 2.5, 95% CI 1.4-4.5, P = 0.002) and diagnosis [other than chronic myeloid leukemia (CML) vs. CML] (RR 2.6, 95% CI 1.2-5.7 P = 0.02).
Our results indicate that the introduction of RIC allogeneic HSCT for patients at high risk for TRM (advanced age, prior HSCT and non-T-cell depletion) leads to a reduction in the TRM and improvement in the OS.
European Journal Of Haematology 03/2005; 74(2):144-51. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Iron overload is associated with free radical generation and tissue damage. Our main objective was to ascertain the frequency and severity of iron overload in a group of 59 patients who died after conventional-intensity autologous (n=24) or allogeneic (n=35) haematopoietic stem cell transplantation (HSCT). A second objective was to investigate associations between liver-iron concentration and causes of transplant-related mortality. The median age was 41 years (range, 19-66), 41 were males and 18 females. In total, 26 patients had acute leukaemia or MDS, 10 CML, 17 lymphoma, four myeloma and two aplastic anaemia. The median hepatic iron concentration (HIC) was 138 micromol/g dry weight (7.7 mg/g; range 31-631 micromol/g). In total, 4/32 (12%) patients with HIC <150 micromol/g and 10/27 (37%) with hepatic iron > or =150 micromol/g showed invasive aspergillosis at autopsy (P=0.035). This was significant in multivariate analysis (RR 9.0; 95% CI 1.6-50.3, P=0.012). In conclusion, severe iron overload is frequent in patients who die following HSCT and is associated with invasive aspergillosis.
Bone Marrow Transplantation 10/2004; 34(6):505-9. · 3.75 Impact Factor
-
M Gómez-Núñez,
R Martino,
M D Caballero,
J A Pérez-Simón, C Canals,
M V Mateos,
J Sarrá,
A León,
C Solano,
J M Moraleda,
A Urbano-Ispizua,
J Besalduch,
J S Miguel,
J Sierra
[show abstract]
[hide abstract]
ABSTRACT: Over a 3-year period, 145 patients ineligible for myeloablative conditioning underwent reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (SCT) from an HLA-identical sibling in a prospective study. The median age was 54 years, 88 patients were male and 61 patients were beyond the early-intermediate phase of their disease. The 100-day probability of developing grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year probability of developing chronic extensive GVHD was 41%. The 1-year probabilities of transplant-related mortality (TRM), overall (OS) and progression-free survival were 20, 60 and 52%, respectively. Multivariate analyses found a better OS in: (i) patients <60 years; and (ii) recipients of a first SCT; and a higher TRM in: (i) age >60 years, (ii) recipients of a prior autologous SCT, and (iii) an ECOG performance status >1. The 1-year TRM in patients with 0 or 1 and >2 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively (P<0.001). In summary, our study shows that elderly patients have a higher TRM following an RIC protocol. However, age by itself should not preclude these RIC transplants, since TRM appears to be unacceptably high only in the presence of additional adverse factors.
Bone Marrow Transplantation 04/2004; 33(5):477-82. · 3.75 Impact Factor
-
D Valcárcel,
R Martino,
D Caballero,
M V Mateos,
J A Pérez-Simón, C Canals,
F Fernández,
J Bargay,
E Muñiz-Díaz,
M Gonzalez,
J F San Miguel,
J Sierra
[show abstract]
[hide abstract]
ABSTRACT: We have performed a prospective study to evaluate early chimerism and its kinetics after allogeneic peripheral blood stem cell transplantation among 68 patients who received a reduced-intensity conditioning (RIC) regimen with fludarabine plus melphalan (n=40) or busulphan (n=28). Chimerism was analyzed by polymerase chain reaction amplification of short tandem repeats in unfractionated (UF) and/or fractionated nucleated cells from bone marrow and peripheral blood (PB). All of the patients showed initial donor engraftment and no patient presented primary or secondary graft failure. In UF samples, the probability of achieving stable complete donor chimerism (CDC) in PB within the first 6 months was 70% on day +30, 85% on day +100 and 95% on day +180. CDC in granulocytes was observed in nearly all cases from day +30 onwards. CDC in T cells, however, differed among melphalan and busulphan recipients during the first 3 months (100 vs 0% on day +30 and 93 vs 20% on day +90, respectively). In multivariate analysis, the only significant variable associated with the achievement of early CDC was having received more than two lines of chemotherapy pretransplant (P<0.02). No correlation was found between the rate of achieving early CDC and the occurrence of acute graft-versus-host disease (GVHD) or disease progression post-transplant. In multivariate analysis, the only variable that influenced the incidence of disease progression post-transplant was the development of chronic extensive GVHD (P<0.05). In conclusion, a state of CDC is readily obtained within the first 6 months after our RIC protocols. Donor myeloid engraftment occurs rapidly in all cases, while early T-cell CDC is more common in more immunosuppressed hosts and, perhaps, in melphalan recipients.
Bone Marrow Transplantation 03/2003; 31(5):387-92. · 3.75 Impact Factor
-
R Martino,
M D Caballero,
J de la Serna,
J L Díez-Martín,
A Urbano-Ispízua,
J F Tomás,
J Odriozola,
A León, C Canals,
J San Miguel,
J Sierra
[show abstract]
[hide abstract]
ABSTRACT: Standard allogeneic stem cell transplantation (SCT) has been associated with a high transplant-related mortality (TRM) in patients who have failed a prior autologous SCT (ASCT). Reduced-intensity conditioning (RIC) regimens may reduce the toxicities and TRM of traditional myeloablative transplants. We report 46 adults who received a RIC peripheral blood SCT from an HLA-identical sibling in two multicenter prospective studies. The median interval between ASCT and allograft was 16 months, and the patients were allografted due to disease progression (n = 43) and/or secondary myelodysplasia (n = 4). Conditioning regimens consisted of fludarabine plus melphalan (n = 41) or busulphan (n = 5). The 100-day incidence of grade II-IV acute graft-versus-host disease (GVHD) was 42% (24% grade III-IV), and 10/30 evaluable patients developed chronic extensive GVHD. Early complete donor chimerism in bone marrow and peripheral blood was observed in 35/42 (83%) patients, and 16 evaluable patients had complete chimerism 1 year post transplant. With a median follow-up of 358 days (450 in 29 survivors), the 1-year incidence of TRM was 24%, and the 1-year overall (OS) and progression-free survival were 63% and 57%, respectively. Patients who had chemorefractory/ progressive disease, a low performance status or received GVHD prophylaxis with cyclosporine A alone (n = 32) had a 1-year TRM of 35% and an OS of 46%, while patients who had none of these characteristics (n = 32) had a 1-year TRM of 35% and an OS of 46% while patients who had none of these characteristics (n = 14) had a TRM of 0% and an OS of 100%. Our results suggest that adult patients who fail a prior ASCT can be salvaged with a RIC allogeneic PBSCT with a low risk of TRM, although patient selection has a profound influence on early outcome.
Bone Marrow Transplantation 08/2002; 30(2):63-8. · 3.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Iron overload (IO) is associated with free radical generation and tissue damage. Our main objective was to ascertain if very high levels (VHL) of ferritin (>/=3000 microg/l) and transferrin saturation (TS) >/=100% during conditioning had an impact on overall survival (OS) and transplant-related mortality (TRM) after a haematopoietic stem cell transplantation (HSCT). Levels of ferritin and TS were measured at days -7 and -4, respectively, in 25 patients who underwent HSCT after CY/TBI. The group consisted of 20 men and five women with a median age of 40 years. Fifteen patients were autotransplanted and 10 allotransplanted. Nine of them had a diagnosis of AL, six of CML and 10 of lymphoma. Thirteen of them were in early and 12 in advanced status of disease. VHL of ferritin and TS >/=100% were associated with a decreased OS (P = 0.001 and P = 0.006, respectively) and an increased TRM (P = 0.003 and P = 0.004, respectively) in univariate survival analysis. Both variables remained significant at multivariate analysis for OS (P = 0.03 and 0.02, respectively) and TS was an independent factor for TRM (P = 0.01). Ferritin was very close to achieving statistical significance for TRM (P = 0.06) in multivariate analysis. In conclusion, VHL of ferritin and TS >/=100% at conditioning are associated with an increase in toxic deaths after transplant.
Bone Marrow Transplantation 06/2002; 29(12):987-9. · 3.75 Impact Factor
-
R Martino,
M D Caballero, C Canals,
J A Simón,
C Solano,
A Urbano-Ispízua,
J Bargay,
C Rayón,
A Léon,
J Sarrá,
J Odriozola,
J G Conde,
J Sierra,
J San Miguel
[show abstract]
[hide abstract]
ABSTRACT: Reduced-intensity conditioning (RIC) regimens for allogeneic haematopoietic stem cell transplantation (SCT) have been shown to lead to engraftment of donor stem cells without the severe extra-haematological toxicities of traditional myeloablative transplants. Between December 1998 and December 2000, 76 patients underwent a RIC peripheral blood SCT in a prospective multicentre study. The median age was 53 years, and 57 patients were beyond the early phase of their disease. The conditioning regimens consisted of fludarabine (150 mg/m2) plus melphalan (140 mg/m2) or busulphan (10 mg/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A plus short-course methotrexate. The preparative regimens were well tolerated. All patients experienced severe pancytopenia, but haematological recovery was prompt in all but two cases (early deaths). The 100-d probability of developing grade II-IV acute GVHD was 32% (10% grade III-IV), and the 1-year probability of developing chronic extensive GVHD was 43%. Early complete donor chimaerism was observed in 52/68 patients, and 16 evaluable patients were in complete chimaerism 1 year post transplant. With a median follow-up of 283 d (355 in 48 survivors), the 1-year probability of transplant-related mortality was 20%, and the 1-year overall and progression-free survivals were 60% and 55% respectively. In conclusion, RIC regimens lead to low early toxicity after allografting, with stable donor haematopoietic engraftment, with an apparent low risk of acute GVHD. Chronic GVHD, however, develops in a significant proportion of patients.
British Journal of Haematology 01/2002; 115(3):653-9. · 4.94 Impact Factor
-
R Martino,
M D Caballero, C Canals,
J San Miguel,
J Sierra,
M Rovira,
C Solano,
J Bargay,
J Pérez-Simon,
A León,
J Sarrá,
S Brunet,
R de la Cámara
[show abstract]
[hide abstract]
ABSTRACT: We compared the occurrence of severe infections following 71 reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplants (PBSCT) and 123 standard myeloablative PBSCT (MINI and STAND groups, respectively) from HLA-identical siblings. The probability of 1-year infection-related mortality (IRM) was 19% in the STAND group and 10% in the MINI group (log-rank, P = 0.3). On multivariate analysis the only significant variable associated with a higher risk of IRM was the development of moderate-to-severe GVHD (P = 0.005). The probability of developing CMV infection was 39% in the STAND group and 21% in the MINI group (P = 0.03) (43% and 21%, respectively, in seropositive donor/recipient pairs, P = 0.01), and the probability of developing CMV disease was 9.5% and 1%, respectively (P = 0.05) (11% and 1%, respectively, in seropositive donor/recipient pairs, P = 0.03). Multivariate analysis of CMV infection identified four variables associated with a higher risk: CMV positive serostatus (P = 0.05), STAND transplant group (P = 0.02), the development of moderate-to-severe GVHD (P < 0.001) and a dose of CD34(+) cells infused below 6 x 10(6)/kg (P = 0.01). Invasive fungal infections and pneumonias of unknown origin did not differ between groups, and neither did other severe non-CMV viral infections and bacterial infections. Our results suggest that RIC allogeneic PBSCT may decrease the risk of dying from an opportunistic infection and reduces the occurrence of CMV infection and disease. Overall, the development of GVHD (acute or chronic) is an important risk factor for these complications. Other infections continue to pose a significant threat to recipients of RIC allografts, stressing that prophylactic and supportive measures are an important aspect in their care.
Bone Marrow Transplantation 08/2001; 28(4):341-7. · 3.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Allogeneic peripheral blood stem cell transplantation with CD34+ cell-selection (CD34+-PBSCT) allows rapid hematologic engraftment with a reduction in graft-versus-host disease (GVHD), although concerns exist regarding the increased risk of tumor relapse associated with T-cell depletion of the graft. Delayed T-cell add-back (TCAB) after such transplants may restore the graft-versus-tumor effect while achieving a reduced early transplant-related mortality due to less GVHD in a group of patients at high risk of early death (i.e., age >= 45 years).
Ten patients 45 years of age or older with hematologic malignancies received a CD34+-PBSCT and cyclosporin A (CyA) to prevent acute GVHD, followed by a planned delayed donor TCAB of 107 T-cells/kg to restore the graft-versus-tumor effect. The infused graft included a median of 6.3x106 CD34+ cells/kg and 4.4x104 CD3+ cells/kg.
Engraftment was prompt in all cases. Four patients developed acute GVHD after the CD34+-PBSCT and/or chronic GVHD after CyA withdrawal and did not proceed to TCAB, and two patients died early before the planned TCAB. Four patients proceeded to TCAB at a median of day +104 after CD34+-PBSCT (+92 to +150). Two of these patients developed acute GVHD grades I-II (IBMTR Index B) after TCAB and all four developed chronic GVHD, which was extensive in two. With a median follow-up of 611 days (range 499-847) after transplant in the seven survivors, there have been no disease progressions, and all patients show a pattern of complete donor chimerism in bone marrow and peripheral blood.
The results of our pilot study suggest that this protocol produces an acceptable transplant-related morbidity and mortality in patients 45 years and older. However, there may be benefit in infusing CD34+-selected PBSCT with even lower T-cell contents and further delaying the TCAB.
Haematologica 11/2000; 85(11):1165-71. · 6.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: High-dose chemo/radiotherapy with autologous stem cell support is increasingly being used in Hodgkin's disease (HD) patients who do not respond to or who relapse after conventional chemotherapy. In this work we analyze the results of 56 consecutive high-risk HD patients autografted in our institution and the role of possible prognostic factors.
There were 34 males and 22 females with a median age of 31 years. At transplantation, 24 patients (43%) were in complete remission and 32 (57%) were autografted while with active disease. Twenty-nine patients were autografted before January 1993. Bone marrow was used as the source of stem cells in 40 patients (71%) and peripheral blood (PB) in 16 (29%). Forty-five patients received chemotherapy-based conditioning regimens (40 CBV and 5 BEAM) while the remaining 11 received cyclophosphamide (Cy) and total body irradiation (TBI).
Two bone marrow transplantation (BMT) recipients did not engraft. Hematologic recovery was significantly faster in patients transplanted with PB progenitor cells. Early transplant-related mortality (early TRM) (before day 100 after transplantation) was 9%; it was higher in patients transplanted before January 1993 than in patients transplanted afterwards (14% vs 4%) and in patients receiving TBI (18% vs 7%), although these differences did not reach statistical significance. Overall TRM (before and after day 100) was 14%. TBI-containing regimens significantly increased overall TRM (36% and 9%, p = 0.03). Actuarial 3.5-year overall survival (OS), event-free survival (EFS) and progression-free survival (PFS) were 57%, 58% and 65%, respectively. On multivariable analysis, TBI containing regimens and transplantation before 1993 significantly reduced OS and EFS.
Our results confirm that high-dose therapy followed by autologous stem cell transplantation is associated with sustained PFS in a remarkable proportion of patients with HD unlikely to be cured with standard chemotherapy. Results improved over time and TBI containing regimens had a negative effect on post-transplant outcome.
Haematologica 03/2000; 85(2):167-72. · 6.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to evaluate the outcome of children with acute lymphoid leukemia (ALL) in second remission who have undergone high-dose chemotherapy and radiotherapy and autologous bone marrow transplantation (ABMT) with monoclonal antibody purged marrow, and to determine the main prognostic factors. From 1987 to 1992, 55 children with ALL in second remission underwent ABMT. The conditioning regimen consisted of total body irradiation (TBI) plus cyclophosphamide in 21 patients and TBI plus cyclophosphamide plus cytarabine or VP-16 in 28 patients; the remaining six patients were treated with chemotherapy alone (cyclophosphamide and busulfan, and/or VP-16). The marrow was purged using monoclonal antibodies and complement or magnetic microspheres in all cases. All patients engrafted. Three patients (5%) died early post transplant from infections. Twenty-six patients (47%) relapsed (median 150 days); 26 patients (47%) are alive and in complete remission (CR) at a median of 36 months. The Kaplan-Meier estimation showed a probability of event-free survival (EFS) of 46 +/- 0.007%. In the univariate analysis, first CR length and conditioning with TBI plus two or more cytotoxic drugs were found to be the most significant predictors of EFS. ABMT with purged marrow is a treatment modality which offers a chance of cure in children with ALL after relapse, including children who relapse early.
Bone Marrow Transplantation 01/1999; 22(11):1043-7. · 3.75 Impact Factor
-
J.A. Cancelas,
S. Querol MD Investigator, C. Canals,
M. Picón,
C. Azqueta,
C. Solà,
A. Montes,
B. Amill,
E. Griera,
J.R. Inglés,
J.J. López,
J.R. Germà,
J. García-López
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Tumor cells have been detected in mobilized peripheral blood of breast cancer patients, and they may contribute to tumor recurrence after the transplantation of peripheral blood progenitor cells. One of the most widespread technologies for tumor purging of the graft is immunomagnetic hematopoietic progenitor cell selection. STUDY DESIGN AND METHODS: The study assessed the effectiveness of a magnetic cell-separation system in selecting functional subpopulations of hematopoietic progenitors from 14 blood-derived harvests of 11 patients with high-risk breast cancer after mobilization following cytotoxic chemotherapy supported by granulocyte–colony-stimulating factor, as well as the feasibility of transplanting these selected subpopulations. RESULTS: CD34(+)-enriched cell fractions had a median purity of 93.0 percent (72.7-98.5%). The procedure yielded 52.6 percent of the CD34+ cell input (39.4-116.8%). Median recoveries of colony-forming units (CFUs) (36.87%) and cobblestone area-forming cells (CAFCs) (152.5%) were, respectively, 0.70 and 2.87 times those of CD34+ cells (52.6%). Moreover, CAFC efficiency in the positive cell fraction was 2.57 times that in the starting cell fraction. Peripheral blood neutrophil counts of 0.5 × 10(9) per L and platelet counts of 20 × 10(9) per L were reached after median times of 9 and 11 days, respectively. The number of transfused CAFCs per kg, CD34+ cells per kg, and postthaw CFU- granulocyte-macrophage per kg was correlated, respectively, with the speed of engraftment of neutrophils, platelets, or both. Tumor cells detected in one patient's peripheral blood were not found after CD34+ cell selection. CONCLUSION: Transplantation of immunomagnetically purified peripheral blood CD34+ cells does not increase transplantation- related morbidity. It induces a selective enrichment of more immature hematopoietic progenitors, which makes it suitable for use in cell expansion and gene therapy protocols.
Transfusion 11/1998; 38(11‐12):1063 - 1070. · 3.22 Impact Factor
-
D Gallardo,
J García-López,
A Sureda, C Canals,
C Ferra,
J A Cancelas,
J J Berlanga,
S Brunet,
C Boqué,
M Picón,
C Torrico,
B Amill,
R Martino,
C Martínez,
G Martín-Henao,
A Domingo-Albós,
A Grañena
[show abstract]
[hide abstract]
ABSTRACT: Based on previous experiences in animals and humans, low doses of CD8+ lymphocytes infused together with the marrow graft seem to enhance engraftment after allogeneic T cell-depleted marrow transplantation. From April 1994 to February 1997, 12 patients with chronic myelogenous leukemia in first chronic phase receiving a bone marrow transplant (BMT) from an HLA-identical sibling were included in a pilot study of T cell subset depletion. Total depletion of CD4+ cells of the marrow graft and partial depletion of CD8+ cells was performed by immunomagnetic separation. In order to improve the engraftment rate, we infused a low fixed number of CD8+ lymphocytes (0.25 x 10(6)/kg). All the patients were at high risk of developing acute graft-versus-host disease (GVHD), with a recipient age of >30 years, and/or donor sensitized by previous pregnancies or transfusions. All of them received cyclosporin A and methotrexate post-BMT. No graft failure was observed. The grade III-IV GVHD rate was 16.6%, and the actuarial survival at 3 years is 81.8%. Immunological recovery showed persistent CD8+ HLA-DR+ lymphocytosis 8 months after transplant. Relapses were not observed. This experience shows the importance of CD8+ cells to ensure correct engraftment, decreasing the GVHD rate.
Bone Marrow Transplantation 12/1997; 20(11):945-52. · 3.75 Impact Factor
-
C Canals,
C Torrico,
M Picón,
B Amill,
J A Cancelas,
G Fraga,
I Badell,
J Cubells,
T Olivé,
J Ortega,
P Vivancos,
J García
[show abstract]
[hide abstract]
ABSTRACT: Autologous bone marrow transplantation (ABMT) offers a therapeutic alternative for children with poor prognosis acute lymphoblastic leukemia (ALL) who lack an HLA-matched sibling donor. The most common cause of treatment failure after ABMT in these patients is leukemia relapse. We have developed an ex vivo autologous marrow purging program for children with ALL using an immunomagnetic method. BM purging has been performed in 37 children with ALL (31 B-lineage ALL and 6 T-lineage ALL) following an indirect method, using panels of mouse monoclonal antibodies (MAbs) directed against B or T cell antigens, Dynabeads M-450 (Dynal) coated with sheep antimouse (SAM) antibodies, and the MaxSep Magnetic Cell Separator (Baxter). Purging efficiency has been assessed by flow cytometry. Considering the limit of detection of target cells 0.1%, the median depletion was 2.0 log (range 0.8- > 2.8 log) for the B-lineage ALL and 2.7 (range 2.2- > 2, 9 log) for the T-lineage ALL patients. Twenty-seven patients have been autografted (6 in first complete remission, CR, 13 in second CR, and 8 in third or subsequent CR). Engraftment has been satisfactory in all of them, reaching levels of 500 neutrophils/mm3 and 20,000 platelets/mm3 after a median of 17 (range 12-39) and 30 (range 13-96) days post-ABMT, respectively. In summary, our results show that this immunomagnetic procedure achieves high levels of target cell depletion and can be safely applied to bone marrow purging in childhood ALL patients.
Journal of Hematotherapy 06/1997; 6(3):261-8.
