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C Canals

Publications and source records attributed to C Canals.

At least 19 recordsLinked to original sources
PubMed2000

Autologous stem cell transplantation for high-risk Hodgkin's disease: improvement over time and impact of conditioning regimen.

BACKGROUND AND OBJECTIVE: 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. DESIGN AND METHODS: 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). RESULTS: 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. INTERPRETATION AND CONCLUSIONS: 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.

Adolescent↗
PubMed2000

Allogeneic peripheral blood stem cell transplantation with CD34+-cell selection and delayed T-cell add-back in adults. Results of a single center pilot study.

BACKGROUND AND OBJECTIVES: 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). DESIGN AND METHODS: 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. RESULTS: 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. INTERPRETATIONS AND CONCLUSIONS: 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.

Antigens, CD34↗
PubMed1998

Autologous bone marrow transplantation with monoclonal antibody purged marrow for children with acute lymphoblastic leukemia in second remission. Spanish Working Party for BMT in Children.

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.

Adolescent↗
PubMed1997

Low-dose donor CD8+ cells in the CD4-depleted graft prevent allogeneic marrow graft rejection and severe graft-versus-host disease for chronic myeloid leukemia patients in first chronic phase.

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.

Adult↗
PubMed1997

Immunomagnetic bone marrow purging in children with acute lymphoblastic leukemia.

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.

Adolescent↗
PubMed1995

CD34+ cell positive selection from mobilized peripheral blood by an indirect immunomagnetic method: effect of the type of mobilization and assessment of tumor depletion ability.

Mobilized peripheral blood has been shown to be a suitable source of hematopoietic progenitor cells for autologous transplantation in oncologic patients. However, tumor cell contamination can potentially occur, although to a lesser extent than in the bone marrow. CD34+ cell positive selection has been developed as a system for the ex vivo purging of remaining tumor cells when used in mobilized peripheral blood. This method has shown a lower purification potential than that obtained with bone marrow or cord blood. The reason for this is not clear, but different groups have tried to improve the purity and yield of the positive selection on mobilized peripheral blood by predepletion of nonlymphoid cell populations, since they can induce nonspecific binding. The present study was designed to test an indirect immunomagnetic CD34+ cell selection method to make it reproducible, feasible, and effective for purging mobilized peripheral blood. Twenty-nine samples from mobilized peripheral blood were tested. The median starting CD34+ percentage was 0.8 (0.3%-4.2%), and the median final purity was 87% (32.7%-99.7%), with a median yield of 44.8% (15%-83.5%). The highest purity was reproducibly achieved when the starting percentage of CD34+ cells was higher than 0.65% (median purity 93.7, range 81%-99.7%, CV 6%) on samples obtained from patients primed with chemotherapy alone or chemotherapy plus recombinant human granulocyte-colony stimulating factor. No relation was found between the content of contaminating nucleated cells and the final CD34+ cell purity. This method showed a depletion capacity, assessed by PCR on samples contaminated with K562 leukemic cells, of about 3 logs. These results indicate that this indirect immunomagnetic method can produce high purity CD34+ cell fractions from mobilized peripheral blood with a high efficiency of tumor depletion.

Antigens, CD34↗
PubMed1995

Presentation of a PCR-nuclease protection strategy for minimal residual disease monitoring in B-ALL.

Methods for detecting residual malignant cells in patients suffering from lymphoid malignancies have neither been sufficiently sensitive nor easy to routinize, hampering a potential prediction of disease outcome. Taking advantage of clone-specific DNA sequences, generated during lymphocyte differentiation and the polymerase chain reaction, some strategies have been developed for several groups. Up to now the most specific and sensitive methodology, which consists of designing leukemia-specific oligonucleotides, requires sequencing of the complementary determining region III-DNA for each particular patient and is too laborious to be applied to each case for routine monitoring in most hospital laboratories. In an attempt to achieve an easy way to detect residual malignant cells in B lymphoproliferative diseases, we have used a new PCR-based approach, named here as PCR-nuclease protection assay, consisting of: (i) amplification of DNA segments corresponding to the complementarity determining region III of the immunoglobulin heavy chain genes from samples at disease diagnosis; (ii) isolation of the disease-specific single-stranded DNA; (iii) labeling of the single-stranded DNA to generate specific probes; (iv) hybridization to amplified DNA from samples corresponding to different disease phases; and (v) digestion with S1-nuclease. Using this approach, we could detect one malignant cell in a background of 10(5) healthy cells. The sensitivity and specificity of this approach compares with those of the above mentioned specific oligonucleotide strategy in detecting residual malignant B cells. Moreover, this strategy is much less tedious and could be used by most hospital laboratories.

Base Sequence↗
PubMed1995

[Unusual presentation of urinary tract infection in 6 cases].

Urinary tract infections may have different clinical presentations that may range from asymptomatic bacteriuria to purulent collections and severe sepsis. We report 6 diabetic patients, 3 presenting with a renal carbuncle and 3 with an emphysematous pyelonephritis. All required medical and surgical treatment and had a good evolution. Two carbuncles were caused by beta- hemolytic type B streptococcus. This is the second notification of this agent as causative of renal abscesses, probably reaching the kidney through hematogenous dissemination from cutaneous foci.

Abscess↗
PubMed1995

[Disseminated nocardiosis in 3 immunocompetent patients].

Nocardia asteroide infections, an aerobic actinomycete, have several forms and lungs, skin and brain are the organs most frequently involved. When the infection suspected, special staining methods must be ordered to identify the agent. We report three immunocompetent patients with disseminated nocardiosis, two presenting with nodular lesions of skin and lungs and one presenting with pulmonary involvement and brain abscesses. The importance of clinical suspicion and early diagnosis of nocardiosis is emphasized.

Adolescent↗
PubMed1994

Bone marrow purging in acute lymphoblastic leukemia: biological and clinical features.

A group of 56 patients with immunophenotyped acute lymphoblastic leukemia had their bone marrow purged using monoclonal antibody (MAb) and complement. Mononuclear marrow cells were treated with panels of MAb directed against T cells (n = 19), CD10-CALLA (n = 16), and B cells (n = 21), resulting in median specific cell depletions of 96.50, 97.59, and 96.97%, respectively. The resulting CFU-GM recoveries were 60.15, 110.6, and 72.9%. Long-term bone marrow cultures showed normal formation of adherent cell layers in 17 of 23 cases, and failure to form an adherent layer correlated with poor hematological reconstitution. A total of 32 patients (aged 4-40 years) received purged marrow grafts containing a median of 1.32 x 10(7) mononuclear cells/kg and 1.64 x 10(4) CFU-GM/kg; 7 patients required backup marrow. Time to engraftment of 500 granulocytes, 1000 leukocytes, 20,000 platelets, and 50,000 platelets was 37, 38, 39, and 57 days, respectively. A total of 16 patients (50%) remain alive and in complete remission 313-913 days posttransplant (median 565 days); 13 patients (41%) relapsed between 50 and 365 days posttransplant (median 100 days), and 3 patients (9%) died from transplant-associated complications.

Adolescent↗
PubMed1994

[Streptococcus pneumoniae septicemia. Analysis of 40 cases].

Sepsis due to Streptococcus pneumoniae has a high mortality. We report a retrospective review of 40 episodes of S pneumonia sepsis in adult patients during a two year period in a general hospital, that represented 11.3% of all sepsis observed in such hospital. Ninety two percent of infections were community acquired and in 95%, the portal of entry was the respiratory tract. Eighty five percent of patients had at least one risk factor such as alcohol abuse, unconsciousness or chronic pulmonary disease. Nine patients had suppurative complications (empyema in 4 cases, spontaneous bacterial peritonitis in 2, septic arthritis in 2 and meningitis in 1 case) and 12 (30%) died. The potential benefit of antipneumococcal vaccine as prevention should be considered in high risk subjects.

Adolescent↗
PubMed1993

Hematological recovery after autologous bone marrow transplantation in acute leukemia: predictive factors.

The kinetics of hematological recovery after autologous marrow transplantation have been studied in 70 patients with acute leukemia (38 acute nonlymphoblastic leukemia [ANNL] and 32 acute lymphoblastic leukemia [ALL]). The incidence of graft failure in this group was 3.2%, and a persistent severe thrombocytopenia was observed in 24% of the cases. Variables influencing engraftment have been studied using univariate and multivariate statistical analysis. Analysis of the entire group showed a correlation between graft colony-forming unit granulocyte-macrophage (CFU-GM) content and granulocyte recovery (p < 0.001). Marrow purging was associated with a delayed engraftment (p < 0.001). In ANLL patients, we found that high cummulated AraC doses before marrow cryopreservation correlated with poor granulocyte recovery after marrow infusion (p < 0.002). Platelet recovery was essentially affected by age, with shorter thrombocytopenia periods in younger patients (p < 0.001). Finally, excluding autotransplants with purged marrows, ALL patients showed better platelet recoveries than ANLL patients (p < 0.005). These findings will be useful to evaluate the risk of delayed engraftment after autologous bone marrow transplantation (ABMT) in patients with acute leukemia.

Acute Disease↗
PubMed1993

Autologous bone marrow transplantation for acute leukemia: results and prognostic factors in 90 consecutive patients.

The results of autologous bone marrow transplantation (ABMT) in acute leukemia (AL) and the prognostic factors for outcome were analyzed in a series of 90 consecutive patients treated at a single institution (mean +/- SD age: 25 +/- 11 years). Diagnosis was: AML (n = 43), ALL (n = 44), acute undifferentiated leukemia (n = 2) and acute bilineage (n = 1). Disease stage at ABMT was: first complete remission (CR1) 46 cases, CR2 33, other stages 11. Conditioning consisted of cyclophosphamide and total body irradiation in 88 patients. The 3 year probability of disease-free survival (DFS) was influenced by disease stage at ABMT: CR1 48%, CR2 28%, CR3 plus CR4 15%. The characteristics associated with a high probability of relapse were: in AML a FAB subtype other than M1 or M3 (p = 0.01) and in ALL an interval between CR1 and ABMT of < 3 months (p = 0.002). A WBC > 15 x 10(9)/l at diagnosis (p = 0.01), splenomegaly at diagnosis (p = 0.002) and time to CR1 > 4 weeks (p = 0.06) increased the risk of relapse in the entire group in CR1. In multivariate analysis, WBC at diagnosis (p = 0.006) and disease stage at ABMT (p = 0.03) independently influenced DFS. This study confirms the encouraging results of ABMT in CR1 but further antileukemia measures are necessary in patients with adverse prognostic features.

Acute Disease↗
PubMed1989

[Association of acute leukemia with disseminated intravascular coagulation in adults. Analysis of 14 cases].

The association of acute leukemia (AL) and disseminated intravascular coagulation (DIC) in 89 patients with a de novo diagnosis of AL made in our center during the last 8 years was retrospectively evaluated. DIC was demonstrated in 14 patients (15.7%) (7 AML-M3, 1 AML-M3, 1 AML-M2, 1 AML-M4, 2 AML-M5, and 2 ALL-L1). In 5 of them ICD was diagnosed after the beginning of chemotherapy. The factors predisposing to the development of DIC were: 1) the type of AL (p less than 0.01), as 70% of AML-M3 had DIC; 2) the intensity of granulation in leukemia cells (p less than 0.004); 3) the presence of Auer's rods and/or splinters in these cells, and 4) the presence of hemorrhagic diathesis (p less than 0.007). Eight of the 14 patients with DIC received heparin at a prophylactic dosage. No significant differences in the clinical course were in the group of patients with DIC who received heparin and in those who did not, excepting that in the former the platelet requirements were higher (p less than 0.005). Mortality rate during the first month was higher in the group of AL with DIC than in AL without DIC (p less than 0.025). Long term mortality was similar in both groups. The control of hemostasis is fundamental in AL, even in those patients without DIC at the time of diagnosis. The administration of blood derivatives has a high priority in AL with DIC. The role of heparin is still controversial.

Adult↗