Summary:Following the cloning of fusion cDNAs resulting from the translocation, several investigators have employed reverse-transcription polymerase chain reaction (RT-PCR) Twenty patients with APL in long-term remission after BMT were analyzed for the presence of the PML-RAR␣ analysis as a diagnostic laboratory test and for evaluation of minimal residual disease (MRD). 4-9 fusion gene by RT-PCR. Ten patients had undergone autologous BMT (six of them peripheral blood stem cell APL is a subtype of AML which is highly responsive to the differentiation agent all-trans retinoic acid (ATRA) transplantation) and 10 allogeneic BMT. A total of 60 samples were examined by two different protocols. Of combined with conventional chemotherapy. Previous molecular monitoring studies of these patients have shown the eight patients studied just before conditioning, five showed PML-RAR␣ transcript prior to transplantation.some points of disagreement with regard to the clinical significance of MRD. Thus, persistence of a positive RT-PCR Three of them were in CR and became PCR negative early post-transplantation. The other two patients, that test for PML-RAR␣ after treatment is highly correlated with subsequent relapse, whereas a negative PCR does not were not in CR before transplant, remained PCR positive, relapsed early post-transplant and died. In the always indicate prolonged remission. [10][11][12][13][14][15] Although APL has a favorable clinical outcome, leukemia relapse remains remaining patients no PML-RAR␣ transcripts were visible throughout their post-BMT courses. Our data show a common problem. A recent retrospective survey 16 indicates that about 45% of APL patients reaching transplant, that long-term remission after BMT in APL patients is associated with eradication of cells carrying the PMLwhether allograft or autograft, are likely to be cured, a result significantly better than for other AML subgroups RAR␣ transcript, and that continued positivity of this test predicts subsequent relapse. The fact of the disapcombined. However, no large series monitoring MRD by RT-PCR and its significance in long survivors after autopearance of PML-RAR␣ transcript early after BMT in patients previously positive suggest that transplant is logous or allogeneic BMT for APL has been published. In this sense, we have serially tested 20 APL patients capable of curing APL mainly through antileukemic action of the conditioning regimen and therefore, transtreated with marrow ablative therapy followed by autograft or allograft using RT-PCR. Our data show that long-term plantation must be indicated in CR patients if a positive RT-PCR remains after treatment with ATRA plus remission of APL after BMT is associated with eradication of cells carrying the specific PML-RAR␣ transcript and that chemotherapy. Keywords: PML-RAR␣; acute promyelocytic leukemia; the continued positivity of this test predicts subsequent relapse. BMT Materials and methods Acute promyelocytic leukemia (APL) is distinct from otherPatients types of acute myelogenous leukemias ...

Summary:The use of peripheral blood stem cells (PBSC) in autolog- In order to determine if peripheral blood stem cells ous transplantation (PBSCT) has demonstrated advantages (PBSC) collected after priming with G-CSF in AML inover the use of marrow (ABMT) in several hematological first complete remission (CR) can be used for autologmalignancies and solid tumors. 1,2 In fact, a faster hematopoous transplantation and to evaluate the efficacy of early ietic reconstitution in PBSCT, resulting in lower infectious intensification therapy as in vivo purging, we studied 35 and haemorrhagic morbidity-mortality than in ABMT, has consecutive patients with AML in first CR. After stanbeen widely observed. 3,4 These advantages are particularly dard induction and consolidation chemotherapy, 24 of evident in patients autografted for acute myelogenous leuthem were treated with one (10 patients) or two (14 kemia (AML), in whom engraftment is slower than in acute patients) cycles of high-dose cytarabine plus etoposide lymphocytic leukemia, and further delays occur as a conseprior to PBSC collection. G-CSF was used as the primquence of purging or heavy chemotherapy administered ing agent. Of the 35 patients scheduled for peripheral before marrow cell harvest. 5,6 In addition, a lower freblood stem cell transplantation (PBSCT), three relapsed quency of neoplastic cells in peripheral blood has been before transplantation, and the 32 remaining underwent reported in this entity. 7,8 PBSCT. High-dose therapy consisted of either totalIn recent years, different methods of mobilization to body irradiation plus cyclophosphamide or busulphan obtain peripheral blood progenitors have been developed. plus cyclophosphamide. The median number of CD34 + High-dose cyclophosphamide or polychemotherapy alone cells infused was 3.24 × 10 6 /kg (range 0.15-14). The or associated with growth factors (mainly GM-CSF or Gmedian times to reach a PMN count of 0.5 × 10 9 /l and CSF) have generally yielded a good number of blood prea platelet count of 50 × 10 9 /l were 12 (8-28) and 30 (11-cursors, enough to assure an early engraftment. 9-12 How-345) days, respectively. There was no transplant-related ever, its use has been considerably reduced because of the mortality. Twelve patients relapsed between 2 and 21 dependence on 'timing' and the additional hematological months post-PBSCT. With a median follow-up of 28 and nonhematological toxicities. Lately, the capacity of a months, actuarial disease-free survival (DFS) is single growth factor to induce mobilization to peripheral 52.41 ؎ 9% in the intent-to-treat group and blood of hematopoietic precursors which are capable of 57.4 ؎ 9.8% in patients who underwent PBSCT. The restoring a complete and sustained hematopoiesis has freprobability of DFS is significantly higher for patients quently been reported. 13,14 Nevertheless, the presence of who receive early intensification therapy prior to both GM or G-CSF receptors in leukemic blast cells, the PBSC collection and PBSCT as compared with patients reported capa...

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.

TRFAM is an effective and safe technique in selected patients for the treatment of metrorrhagia secondary to myomas.

Ascertaining the vital origin of skin wounds is one of the most challenging problems in forensic pathology. The forensic literature describes biomarkers and methods for differentiating vital and postmortem wounds, although no clear conclusions have been reached. The aim of this study was to characterize human vital wounds by analyzing the concentrations of metallic ions and the expression of P-selectin and cathepsin D in skin wounds in the ligature marks in a cohort of suicidal hangings for which vitality was previously demonstrated.A total of 71 skin wounds were analyzed within a postmortem interval of 19 to 36 hours. The concentration of Fe, Zn, Mg, and Ca and the expression of P-selectin and cathepsin D were analyzed together and separately. The majority of autopsied suicidal hangings were men (86%) with complete hanging mode (60.7%) in which there was a high frequency of subcutaneous injuries (78.3%). High concentrations of Ca and Mg compared with Fe and Zn were found. Ca and Zn concentrations decreased, and Fe concentration increased with the seriousness of the injury. A high percentage of moderately negative expression of both proteins was correlated with subcutaneous injury and low or medium concentrations of Fe.In conclusion, the joint study of metallic ions and proteins allows to characterize and to differentiate an injured vital wound of noninjured skin, especially when the damage in the tissue affects to the majority of the structures of the skin, but these results will need to be complemented with other biomarkers in time-controlled samples to further help in the differentiation of vital and postmortem wounds.