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J Sanchez-Garcia, J Serrano,
J Serrano-Lopez,
P Gomez-Garcia,
F Martinez,
J M Garcia-Castellano,
R Rojas,
C Martin,
A Rodriguez-Villa,
J R Molina-Hurtado,
M A Alvarez,
J Casaño,
A Torres-Gomez
[show abstract]
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ABSTRACT: The potential impact on patient outcome of different Minimal residual disease (MRD) levels at time of transplant in patients with lymphoblastic leukemia undergoing allogeneic hematopoietic SCT (HSCT) remains uncertain. In this study, we quantified MRD levels at time of transplant using multiparameter flow cytometry (MFC). Mononuclear cells from marrow aspirates were obtained from 102 adult and child patients before their conditioning regimen. Quantification of MRD levels was carried out by detecting patient-specific leukemia-associated immunophenotypes using four-color MFC. Thirty patients exhibited measurable levels of MRD at the time of transplant, with low levels (0.01 to 0.1%) in 12 cases, intermediate levels (>0.1 to 1%) in 8 cases and high levels (>1%) in 10 cases. The leukemia-free survival (LFS) rates were 65.9±7.0%, 42.9±15.7% and 0% for negative, low levels 0.1% and intermediate-high levels >0.1%, respectively (P<0.001, log-rank test). Overall survival (OS) was 52.3±7.6%, 28.6±13.8% and 0% for MRD-negative, low levels 0.1% and intermediate-high levels >0.1%, respectively (P<0.001, log-rank test). Multivariate Cox analysis confirmed that detection of leukemia cells by flow cytometry at transplant was the most significantly adverse factor for OS, LFS and EFS after transplant.Bone Marrow Transplantation advance online publication, 30 July 2012; doi:10.1038/bmt.2012.147.
Bone marrow transplantation 07/2012; · 3.00 Impact Factor
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J R Molina, J Serrano,
J Sánchez-García,
A Rodríguez-Villa,
P Gómez,
D Tallón,
V Martín,
G Rodríguez,
R Rojas,
C Martín,
F Martínez,
M A Alvarez,
A Torres
[show abstract]
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ABSTRACT: Invasive fungal disease (IFD) causes significant morbidity and mortality among children undergoing allo-SCT. In this prospective pilot study, we analyze voriconazole as primary antifungal prophylaxis. From October 2004 to July 2010, 56 children <18 years of age were enrolled in this study. Patients received voriconazole doses of 5 mg/kg per 12 h (n=23) or 7 mg/kg per 12 h (n=33), with a limiting dose of 200 mg/12 h, from day -1 to day +75 or later in patients with active acute GVHD. Patients were followed up for IFD for 6 months. In this series, 37 (66.1%) patients successfully completed treatment (85.7% during neutropenic period) without empirical or preemptive antifungal therapy, adverse effects or IFD. Nine (16.1%) children needed preemptive (n=2) or empirical (n=7) antifungal therapy, and one (1.8%) of them developed a fatal probable IFD during the study period. A total of 10 (17.8%) children developed adverse effects related to voriconazole prophylaxis, leading to definitive withdrawal on median day 26.5 (in 7 patients after granulocytic recovery). The most frequent adverse effect was persistent elevation of hepatic enzymes in seven (12.5%) children. There were no differences between doses of 5 and 7 mg/kg per 12 h. Our results suggest that voriconazole can be safely used as primary antifungal prophylaxis in children undergoing allo-SCT.
Bone marrow transplantation 05/2011; 47(4):562-7. · 3.00 Impact Factor
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ABSTRACT: Early detection of donor-derived hematopoietic restoration after allogeneic stem cell transplantation (allo-SCT) is a crucial issue in the management of heavily immunocompromised patients. The aim of this prospective study was to validate our previously defined cutoff values for reticulocyte maturation parameters as early predictors of hematopoietic engraftment. Importantly, the effect of clinical variables in reticulocyte engraftment was also sought. For this purpose, we prospectively studied 136 consecutive patients undergoing allo-SCT from related (n = 89) or unrelated (n = 47) donors. High fluorescence reticulocytes (RETH), immature reticulocyte fraction (IRF), mean fluorescence index (MFI), and mean reticulocyte volume (MRV) were automatically measured in peripheral blood samples drawn on a daily basis. We previously defined reticulocyte engraftment when MFI > or =10, RETH > or =3%, IRF > or =10%, and MRV > or =110 fL. Median neutrophil engraftment was 18 days (range, 10-35 days); for reticulocyte parameters, the values were 14 days for IRF (range, 7-45 days), 14 days for MFI (range, 7-43 days), 15 days for RETH (range, 7-43 days), and 21 days for MRV (range, 9-74 days). These differences reached statistical significance for MFI and IRF when compared with standard neutrophil recovery, even when analyzing siblings or unrelated donors separately. In univariate analysis, donor-recipient ABO disparity adversely influenced erythroid engraftment (P = .04 for IRF, P = .03 for MFI), but the infusion of >2.9 x 10(6)/kg of CD34+ cells was associated with a shorter time to reach erythroid engraftment (P = .02 for IRF and MFI). In Cox regression analysis, > or =100/microL neutrophils and IRF > or =10% were predictive parameters for standard neutrophil engraftment. Based on these findings, we suggest that serial measurement of IRF or MFI should be routinely used to trace hematopoietic restoration after allo-SCT because these preceded standard neutrophil recovery by a median of 4 days and are therefore very useful to make clinical decisions.
Biology of Blood and Marrow Transplantation 03/2007; 13(2):172-82. · 3.87 Impact Factor
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J Serrano,
F Lo Coco,
T Sprovieri,
L Elia,
A Vitale,
C Gregorj,
A Tafuri,
J Sánchez,
J Román,
A Torres,
G Cimino
[show abstract]
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ABSTRACT: In this study, we examined myeloperoxidase (MPO) gene expression in a series of 31 non-infant pro-B acute lymphoblastic leukaemia (ALL) patients that included 16 cases with the t(4;11) translocation and/or the resultant ALL1/AF4 chimaeric gene. Sixteen out of 31 cases (51%) were MPO mRNA positive/enzyme negative. MPO mRNA was detected in nine out of 16 (56%) and seven out of 15 (47%) patients with and without the ALL1/AF4 fusion transcript respectively. The comparative study between MPO mRNA positive and negative cases showed statistically significant differences with regard to age and white blood cell (WBC) count, and was 39.5 years vs. 26.3 years (P = 0.016) and 71.4 x 10(9)/l vs. 157.8 x 10(9)/l (P = 0.046) in the MPO mRNA positive and negative groups respectively. The correlation analysis between MPO mRNA expression, age, WBC count and leukaemic relapse according to the presence/absence of the ALL1/AF4 fusion showed that the statistically significant differences observed in the whole group were related mostly to the ALL1/AF4-positive ALL patients. In fact, in this latter group, the mean WBC count and patients' age were 85 +/- 79 x 10(9)/l vs. 289.8 +/- 102 x 10(9)/l (P = 0.0005) and 44.8 +/- 15.3 years vs. 26.7 +/- 13.7 years (P = 0.01) in patients with and without MPO mRNA expression respectively. It appears, therefore, that the assessment of MPO mRNA expression enables a further dissection of leukaemia heterogeneity in apparently homogeneous genetic/immunophenotypic ALL subsets.
British Journal of Haematology 01/2001; 111(4):1065-70. · 4.94 Impact Factor
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A Torres,
J Sánchez,
D Lakomsky, J Serrano,
M A Alvarez,
C Martín,
C Valls,
L Nevado,
A Rodriguez,
J Casaño,
F Martínez,
P Gómez
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ABSTRACT: Hematopoietic restoration after marrow ablation is initiated by the erythroid compartment. However, the absolute microscope counts or corrected percentage of reticulocytes have proven to be poor markers of hematopoietic engraftment. Some reports have highlighted the usefulness of automatic flow cytometry methods to determine highly fluorescent reticulocytes, or mean fluorescence index. In this series of 60 hematopoietic stem cell transplants, we sought the normal kinetics throughout the post-transplant period of the following reticulocyte maturing parameters: highly fluorescent reticulocytes (RETH), immature reticulocyte fraction (IRF), mean fluorescence index (MFI) and also mean reticulocyte volume (MRV).
Sixty consecutive patients undergoing allogeneic bone marrow (30 cases) and autologous mobilized stem cell transplantation (30 cases) were studied. Parameters of reticulocyte maturation were measured every other day from the beginning of the conditioning regimen until myeloid engraftment.
Nadir values for the analyzed reticulocyte parameters were found between days +4 and +7 and thereafter, increases in these reticulocyte parameters appeared earlier than the rise in neutrophils. We considered erythroid engraftment to have occurred on the day when RETH reached 3%, IRF 10%, MFI 10 and MRV 110 fL. These cut-offs were assigned considering the 25% quartile for each parameter on the day that the myeloid engraftment occurred. The median engraftment days for RETH were +9 and +16, for IRF +9 and +13, for MFI +9 and +13 and for MRV +11 and +13 in autologous and allogeneic procedures, respectively. When compared to standard neutrophil engraftment, IRF and MFI engraftment occurred significantly earlier in all patients. Remarkably, we found a statistical correlation between the day a reticulocyte parameter reached its cut-off and the subsequent day of absolute neutrophil count (ANC) recovery for MFI after allogeneic transplants and for MRV after autologous procedures (p < 0.001 and p= 0.02, respectively). Of all the clinical parameters tested, only the number of infused CD34 cells showed a statistical influence on erythroid engraftment in autologous transplant.
Early reticulocytes appear sooner than neutrophils after both autologous and allogeneic transplants, and any determined reticulocyte parameter can reliably measure this fraction. Nevertheless, our results show that MRV and MFI cut-offs are useful for determining subsequent myeloid engraftment. These findings could be relevant to decision-making in those patients with primary graft failure heralded by an absence of increasing values of MFI and MRV, indicating very low production of reticulocytes from the graft, who could, therefore, benefit from earlier rescue therapy.
Haematologica 01/2001; 86(1):24-9. · 6.42 Impact Factor
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Haematologica 05/2000; 85(4):434-5. · 6.42 Impact Factor
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J Serrano,
J Roman,
J Sanchez,
A Jimenez,
J A Castillejo,
C Herrera,
M G Gonzalez,
L Reina,
M C Rodriguez,
M A Alvarez,
J Maldonado,
A Torres
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ABSTRACT: We studied lineage-specific chimerism and minimal residual disease (MRD) in sequential posttransplant samples from 55 patients who underwent unmanipulated (n = 44) or partially T-cell-depleted (n = 11) allogeneic bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). Chimerism was assessed by polymerase chain reaction (VNTR [variable number of tandem repeats]-PCR) analysis in highly purified CD19+, CD3+, CD15+, and CD56+ cell fractions, whereas MRD was investigated in whole blood by reverse transcriptase-PCR (RT-PCR) of both p210(BCR-ABL) and p190(BCR-ABL) hybrid transcripts. Of 55 patients, 14 (including 6 T-cell-depleted patients) had cytogenetic relapse at 5-80 months and progressed to hematologic relapse, while 41 patients remained in prolonged cytogenetic remission 12-107 months post-BMT. Before leukemia recurrence, patients in the relapse group showed a consistent evolution pattern sequentially featured by persistent p210(BCR-ABL) positivity, increasing mixed chimerism (MC) in myeloid cells, p190(BCR-ABL) positivity, and, finally, cytogenetic relapse. Myeloid MC preceded cytogenetic relapse by 2-12 months, whereas p190(BCR/ABL) was detected 1-6 months prior to cytogenetic relapse in 11 patients and concomitant with cytogenetic relapse in 3 patients. In the remission group, all patients invariably tested negative for p190(BCR-ABL); 10 patients tested positive for p210(BCR-ABL) at variable time-points but showed persistent full donor chimerism (DC), whereas 31 patients tested p210(BCR-ABL) negative and displayed full DC or transient MC due to the persistence of recipient T cells. Two patients in the relapse group were successfully reinduced into molecular remission with donor lymphocyte infusion. Sequential molecular analysis after such treatment showed the inverse pattern to that observed prior to relapse, ie, progressive disappearance of p190(BCR-ABL) transcripts, conversion of myeloid chimerism to donor type, and, finally, p210(BCR-ABL) negativity. We conclude that lineage-specific chimerism and p190(BCR-ABL) messenger RNA (mRNA) analyses contribute a better characterization of CML evolution after BMT and enable early identification of patients at the highest risk of relapse. (Blood. 2000;95:2659-2665)
Blood 05/2000; 95(8):2659-65. · 9.90 Impact Factor
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J Román, J Serrano,
A Jiménez,
J A Castillejo,
M L Reina,
M G González,
M C Rodríguez,
I García,
J Sánchez,
J Maldonado,
A Torres
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ABSTRACT: Although bcr-abl polymerase chain reaction (PCR) positivity after bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) is significantly related to relapse, the predictive value of the assay is not very high and therefore most investigators consider that qualitative RT-PCR data alone are too imprecise to enable clinical decisions to be taken in individual cases. To define the clinical outcome of bcr-abl positive patients after unmanipulated BMT better, we sought the origin of hematopoiesis and traced its evolution over time.
Forty-nine patients received allogeneic BMT for CML (39 in chronic phase and 10 in accelerated phase/blast crisis). Median follow-up was 61 months (range 4-92). mRNA and DNA were used to assess bcr-abl and chimerism status respectively. Quantitative VNTR-PCR on total cells and lymphoid or myeloid population allowed us to assign and measure the origin of hematopoiesis.
Both bcr-abl positivity and the presence of mixed chimerism (MC) were significantly associated with relapse (p = 0.0009 and p < 0.0001 respectively). Relapse was observed in one of 39 patients with complete donor chimerism and in 6 of 9 patients with MC. These six cases showed increasing levels of host hemopoiesis and bcr-abl positivity in the CD15-positive population prior to relapse. The other three cases had decreasing or stable low-level MC which was restricted to the T-cells as well as bcr-abl negativity.
Whereas the simple detection of bcr-abl fails to identify patients who will relapse with certainty, the assessment of MC by VNTR-PCR does identify patients headed to relapse. Confirmation of myeloid involvement and increasing levels over time further elucidates the clinical outcome of bcr-abl positive patients after BMT.
Haematologica 02/2000; 85(2):173-80. · 6.42 Impact Factor
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Haematologica 09/1999; 84(8):762-3. · 6.42 Impact Factor
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A Torres,
M A Alvarez,
J Sánchez,
R Flores,
F Martinez,
P Gómez,
R Rojas,
C Herrera,
J M García,
P Andrés, [......],
S Tabares,
J M Rodriguez,
R Parody,
E Plaza,
A León,
R Romero,
E Jean-Paul,
D Prados,
R Aljama,
A Fernández
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ABSTRACT: In 1989 we carried out a trial comparing allogeneic BMT to chemotherapy (CT) in 76 children with relapsed acute lymphoblastic leukaemia (ALL). Ten years on we have clinically revised outcome to firmly establish the role of each treatment, to analyse the importance of length of first remission and to provide long-term actuarial results for disease-free survival (DFS) and relapse rate in each group. For 21 patients within the transplantation group, probability of DFS and relapse are 42.8 +/- 10.8% and 40.2 +/- 11.7% (s.e.), respectively. In the chemotherapy group, probability of DFS is 10.0 +/- 4.74% (P = 0.001) and probability of relapse 87.5 +/- 5.2% (P = 0.0004). These results strongly reflect those at initial analysis, confirming a key role of BMT in the management of ALL in second remission. Moreover, on univariate analysis only two factors influenced DFS: treatment group and length of first complete remission (less or more than 30 months from first CR). Thus, it seems clear that the best therapeutic option in early relapse is BMT, whereas DFS in late relapse is at the limit of significance (P = 0.07), with a higher relapse rate in the CT group. Although encouraging results using intensified rotational combination chemotherapy have been published, prospective randomised studies are needed to assess with certainty the best therapeutic option in these patients.
Bone Marrow Transplantation 07/1999; 23(12):1257-60. · 3.75 Impact Factor
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J Serrano,
J Román,
C Herrera,
J A Castillejo,
J A Navarro,
M L Reina,
M G González,
M C Rodriguez,
A Pascual,
J Sánchez,
A Torres
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ABSTRACT: In this study we analysed the incidence and clinical impact of the persistence of host haemopoiesis (mixed chimaerism, MC) after allogeneic BMT in 35 consecutive patients with haematologic malignancies using a total CD4+ cell-depleted graft with an adjusted dose of CD8+ cells (1x10(8)/kg). Chimaerism was assessed by PCR amplification of VNTRs in 30 evaluable patients: 19 non-CML and 11 CML cases which were also evaluated for the BCR-ABL transcript by RT-PCR. All but one had complete engraftment with a donor profile early post-BMT. At the end of the study period, 12 of 30 patients displayed MC (40%). The overall disease-free survival for MC patients was clearly unfavourable when compared to those who exhibited a donor profile (24.7% vs. 100%, P = 0.005). However, we found that only two of five patients with MC in the non-CML group relapsed, whereas a clear correlation could be made between MC and relapse in CML (seven showed MC, preceding cytogenetic or haematological relapse in six of them, which displayed a prior BCR-ABL mRNA positivity). In addition, a quantitative-PCR approach enabled us to demonstrate that increasing amounts of MC are invariably associated with subsequent relapse, whereas a low stable level of host or complete donor haemopoiesis is consistent with clinical complete remission. Although these results suggest that the clinical impact of MC may depend on the underlying disease, it is compatible with the concept that the graft-versus-leukaemia effect against CML is mainly exerted by donor CD4+ lymphocytes. Elimination of this cellular subset may be responsible for the inability of the graft to prevent a progressive increase in the tumor cell burden.
Bone Marrow Transplantation 04/1999; 23(5):475-82. · 3.75 Impact Factor
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ABSTRACT: From March 1994 to September 1997, 30 patients with hematological malignancies (12 ANLL, 10 CML, four ALL and four multiple myeloma) received HLA-identical allogeneic bone marrow transplants with the marrow graft selectively depleted of CD4+ lymphocytes and the CD8+ cell content adjusted to 1x10(6)/kg. Total depletion of CD4+ and partial depletion of CD8+ lymphocytes was carried out by an immunomagnetical method. All patients were considered as having high risk for developing GVHD by at least one of the following criteria: patient age >35 years; donor age >35 years; donor multiparity or marrow from an unrelated donor. Twenty-four cases received marrow from an identical sibling and six from an unrelated donor. In order to assess the role of methotrexate (MTX) in addition to cyclosporin A (CsA) after transplant, patients were randomly assigned to received either CsA alone (n = 15) or CsA plus a short course of MTX (n = 15). No case of primary graft failure was observed, but two patients developed late graft failure. Six patients presented grade II acute GVHD and no case of severe III-IV GVHD was seen. The actuarial probability of developing grade II-IV acute GVHD was 25.9+/-9.6% for the entire population. Patients receiving post-transplant CsA + MTX had significantly less probability of acute GVHD than those receiving CsA exclusively (6.7+/-6.4% vs. 50.5+/-17.8%, P = 0.03) and the schedule of post-transplant immunosuppression was the only factor associated with the incidence of acute GVHD in a multivariate analysis. The actuarial incidence of chronic GVHD for the entire population was 31.8+/-12.5, and there was no significant difference between both groups with additional prophylaxis. Four patients with CML and three with ANLL relapsed: the actuarial probability of remaining in complete remission for all patients was 53.6+/-17.3%. For patients with acute leukemia, the probability of remaining in complete remission did not differ significantly between those transplanted in first complete remission and those receiving a transplant in more advanced phases of the disease (87.5+/-11.6% vs. 72.9+/-16.5%; P = 0.44). The incidence of mixed chimerism assessed by PCR was 34%. Nineteen patients are alive between 2 and 43 months post-transplant, the probability of overall survival being 57.8+/-10.4%. Our data indicate that this method of selective T cell depletion is very effective in preventing acute GVHD in high risk patients, particularly when used in combination with post-transplant CsA + MTX.
Bone Marrow Transplantation 04/1999; 23(5):443-50. · 3.75 Impact Factor
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ABSTRACT: Myeloperoxidase (MPO) is found in the azurophilic granules of normal myelocytic cells. Cytochemical staining for MPO activity is used clinically to distinguish myeloid from acute lymphoid leukemias (ALL). However, using a highly sensitive RT-PCR technique, it is possible to detect MPO mRNA in otherwise clear ALL. The significance of this finding remains poorly understood. We have extended our observations to a series of 57 patients with the primary diagnosis of ALL (46 patients tested at diagnosis and 11 cases at relapse). We identified 25 cases (43.8%) of MPO mRNA(+)/enzyme(-) ALL (17 B cell and eight T cell lineage). Expression of myeloid antigens (CD13 or CD33) were detected in nine of them, and remarkably, 18 cases (72%) displayed CD34. Of these 25 MPO mRNA(+) leukemias, 10 (40%) are Bcr-Abl positive (with P210 fusion transcript in five patients while the five remaining cases carried P190 transcript). Moreover, 11 of 16 myeloid negative cases were also negative for any type of Bcr-Abl and MLL rearrangement, indicating that MPO mRNA positivity is not either invariably related to that chromosomal abnormality or necessarily associated with the presence of other myeloid differentiation features. Interestingly, six of these 11 cases are T-ALL, suggesting the presence of some overlapping phase for T and myeloid lineage commitment. Taken together, these findings could suggest a separate biological disease with immature origin and bipotential differentiation capability, which involves B and T-ALL subtypes and should lead to new investigations regarding their prognostic impact.
Leukemia 03/1999; 13(2):175-80. · 9.56 Impact Factor
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ABSTRACT: To evaluate the relationship between clinical parameters and the ability to detect BCR-ABL-positive cells in a series of 27 long survivor patients after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML).
A total of 78 samples obtained between 1 and 160 months after BMT were analyzed for the presence of the BCR-ABL transcript detected by the reverse-transcription polymerase chain reaction (PCR) using nested primers. Median follow up was 83 months.
16 patients were persistently PCR-positive and 7 patients persistently PCR-negative. The original transcript became negative in four patients. Only two of the positive cases developed hematologic relapse during the period of study. High white blood cell counts before BMT (17.88 vs 10.12 x 10(9)/l; p = 0.008) and immunosuppressive therapy for chronic graft-versus-host disease (p < 0.05) were associated with an increased ability to detect residual BCR-ABL positive cells.
Our data show that most patient are persistently BCR-ABL positive after BMT for CML. If these findings represents a dynamic balance between the tumour burden prior BMT and the immunological capability of the graft must be confirmed in further studies.
Medicina Clínica 11/1998; 111(11):405-9. · 1.38 Impact Factor
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ABSTRACT: We report a patient with Ph chromosome-positive CML who underwent an HLA-identical T cell-depleted BMT from a sibling donor. DNA polymorphism analysis showed complete donor chimaerism after BMT, followed by mixed chimaerism of granulocytes, natural killer cells and B lymphocytes, with T lymphocytes host-derived at day +120 post BMT. From month +20 haematopoiesis was exclusively of host origin in all cell lineages. RT-PCR was used in order to detect residual disease, but at the time, analysis did not show BCR-ABL transcripts. This case is unusual in that non-malignant stem cells of recipient origin survived the transplant and reconstituted haematopoiesis after BMT. Two years post transplant, no molecular or haematological relapse was documented. The observation that subsequent recipient recovery without molecular relapse implies that, at least in this case, the GVL effect can occur in the absence of donor T cells.
Bone Marrow Transplantation 10/1998; 22(6):599-601. · 3.75 Impact Factor
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Dermatology 02/1998; 196(3):370-1. · 2.05 Impact Factor
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C Martín,
A Torres,
A León,
V Rubio,
M A Alvarez,
C Herrera,
E Jean-Paul,
M A Correa,
R Rojas,
R Campos, J Serrano,
R Romero,
J Román,
J L Guzmán,
R Flores,
M Falcón,
F Martínez,
P Gómez
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ABSTRACT: In order to determine if peripheral blood stem cells (PBSC) collected after priming with G-CSF in AML in first complete remission (CR) can be used for autologous transplantation and to evaluate the efficacy of early intensification therapy as in vivo purging, we studied 35 consecutive patients with AML in first CR. After standard induction and consolidation chemotherapy, 24 of them were treated with one (10 patients) or two (14 patients) cycles of high-dose cytarabine plus etoposide prior to PBSC collection. G-CSF was used as the priming agent. Of the 35 patients scheduled for peripheral blood stem cell transplantation (PBSCT), three relapsed before transplantation, and the 32 remaining underwent PBSCT. High-dose therapy consisted of either total body irradiation plus cyclophosphamide or busulphan plus cyclophosphamide. The median number of CD34+ cells infused was 3.24 x 10(6)/kg (range 0.15-14). The median times to reach a PMN count of 0.5 x 10(9)/l and a platelet count of 50 x 10(9)/l were 12 (8-28) and 30 (11-345) days, respectively. There was no transplant-related mortality. Twelve patients relapsed between 2 and 21 months post-PBSCT. With a median follow-up of 28 months, actuarial disease-free survival (DFS) is 52.41 +/- 9% in the intent-to-treat group and 57.4 +/- 9.8% in patients who underwent PBSCT. The probability of DFS is significantly higher for patients who receive early intensification therapy prior to both PBSC collection and PBSCT as compared with patients that do not: 68.8 +/- 10.27% vs 35.5 +/- 12.6%, P = 0.0418. These results indicate the feasibility of PBSCT in AML using G-CSF-mobilized PBSC. The use of intensification treatment as 'purging in vivo' prior both to collection of PBSC and PBSCT significantly reduces the risk of relapse in this group of patients.
Bone Marrow Transplantation 02/1998; 21(4):375-82. · 3.75 Impact Factor
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ABSTRACT: A 16 year old man underwent an allogeneic bone marrow transplantation (BMT) from an HLA identical sibling donor for acute lymphoblastic leukaemia in 1984. He developed chronic graft versus host disease involving the skin and kidneys. At day 400 after BMT his condition was complicated by obstructive airways disease, which was partially responsive to azathioprine and steroids. Five years after withdrawal of immunosuppressive treatment he developed dyspnoea and decreased pulmonary function test results, and steroid treatment was resumed. Fibrobronchoscopy revealed the presence of a mucoepidermoid carcinoma in the left main bronchus. After surgical laser resection, there was gradual clinical and functional improvement. There was no evidence of recurrence one year after surgery.
Journal of Clinical Pathology 12/1997; 50(11):969-70. · 2.31 Impact Factor
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ABSTRACT: To describe clinical outcome with first line immunosuppression therapy for obstructive airways disease (OAD) after allogeneic BMT, we have retrospectively examined 20 long-term survivors affected by OAD. All patients had normal pulmonary function test (PFTs) before BMT. OAD was defined as FEV1 less than 80%, FER less than 80%, maximum midexpiratory flow rate of 50% vital capacity (MMFR) less than 65%, or residual volume greater than 120. Prednisone (n = 4), CsA (n = 8) and azathioprine (n = 8) have been used as first-line immunosuppression agents. Mean follow-up was 65 months (range 15-142). We identified three categories of patients according to response to treatment: complete (n = 6, 30%), partial (n = 6, 30%) or no response (n = 8, 40%). Age, FEV1, time of onset after BMT, Karnofsky index or immunosuppression modality do not seem to be related to subsequent response. However, patients with low values of MMFR and high values of RV at the beginning of therapy are likely to show poor response. In the complete response group, normalisation of PFTs is achieved within the first months of treatment (median 6 months ranging from 3 to 9 months), suggesting that prolonged therapy is not advantageous and could increase morbidity and mortality if there are no other signs of CGVHD.
Bone Marrow Transplantation 10/1997; 20(5):403-8. · 3.75 Impact Factor
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ABSTRACT: The FAB classification of acute leukaemias is based on the light microscopic detection of myeloperoxidase (MPO) activity in blast cells. Cases with MPO activity in > or = 3% of blasts are classified as acute myeloid leukaemia. We describe two cases of acute leukaemia in which the blast cells had lymphoid morphology, ultrastructure, immunophenotype and molecular rearrangements, but expressed significant levels of the MPO gene (MPO mRNA) by reverse transcription polymerase chain reaction (RT-PCR), in the absence of translation to protein. Both cases presented a short remission duration. We discuss the incidence, features and outcome of MPO mRNA positive acute lymphoblastic leukaemia (ALL).
British Journal of Haematology 07/1997; 97(4):841-3. · 4.94 Impact Factor
