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 ...

Determination of hematological chimerism could be helpful in understanding the biology of leukemic relapse after allogeneic bone marrow transplant (BMT) for chronic myeloid leukemia (CML), because the detection of malignant residual cells carrying the bcr/abl message by qualitative RT-PCR is of limited value in predicting disease progression for individual patients. We have studied the chimerism pattern and the bcr/abl status by Southern-blot in 15 CML patients (M/F:6/9) transplanted with unmanipulated BM from HLA identical sibling donors, persistently bcr/abl positive by RT-PCR. The median age of the series was 31 years (18-49) and disease status at BMT was: chronic phase: 11, accelerated phase: 3 and blast crisis: 1 patient. Of the 15 patients, 9 are alive and in complete remission (CR), 4 have died in CR and 2 are alive but suffered relapse at + 19 and +26 months post-BMT. The median follow-up is 81 months (13,7-168). Rearrangement of the BCR gene was performed by Southern-blot using P32-labeled transprobe-1. PCR analysis of chimerism was assessed using primers for the following VNTR loci: D1S80, D1S111, 33.1, APO-B, YNZ-22, lambdag3 and DXS52. Seventy-nine samples were analyzed (median per patient 5 (range 2-9)). Thirteen patients showed complete chimerism and lacked BCR rearrangement over time by Southern-blot. The 2 patients who relapsed showed mixed chimera status from +9 and +5 months respectively until the end of the study. Persistent BCR rearrangement was observed in these 2 patients from +12 and +11 months respectively. Our data suggest that mixed chimerism may predict hematologic or cytogenetic relapse by several months in those patients who are persistently PCR-positive post-BMT.

Summary: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. Keywords: BMT vs chemotherapy; childhood ALL; second CR; revisited In 1989, we concluded that allogeneic bone marrow transplantation (BMT) is the best alternative therapy for children with ALL who have relapsed in their marrow. 1 In that report, we prospectively studied 76 such patients, 21 of whom had a genotypically identical HLA donor and underwent allogeneic BMT. The remaining 55 patients who lacked a suitable donor, received conventional chemotherapy (CT). Probability of survival was significantly higher in the BMT group (47.1 ± 11.7% vs 9.2 ± 5.6%, P Ͻ 0.025). Probability of remaining in complete remission in the BMT group was 58.5% vs 10.9% in the chemotherapy group (P Ͻ 0.005).At the time of publication of those findings and as a consequence of the discouraging results initially obtained by some groups with BMT for ALL patients in second CR, 2,3 many controversies arose, such as whether or not these children should undergo allogeneic BMT. [4][5][6][7] In the last 10 years, despite the lack of well-designed randomised studies with large numbers of patients, all results seem to confirm that high-dose chemotherapy and bone marrow transplantation from an histocompatible donor afford a greater chance of leukaemia-free survival than does conventional chemotherapy. However, it has been recently pointed out 8 that indications for BMT in ALL are not fully established, because of publications involving small numbers of patients, difficulties over selection bias since most patients lack a suitable sibling donor, and importantly, that a very long follow-up is needed to assess results of a second course of chemotherapy.On the other hand, it has been stated th...

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