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PubMed2006

Patterns of C-reactive protein release following allogeneic stem cell transplantation are correlated with leukemic relapse.

The C-reactive protein (CRP) is an acute-phase protein produced by hepatocytes, and is a reliable marker of systemic inflammation, which is relevant to the release of the proinflammatory cytokines. The value of monitoring the CRP levels after stem cell transplantation (SCT) can identify patients at risk of treatment-related complications and mortality. Inflammatory cytokines facilitate donor T-cell activation via antigen presenting cells immediately after SCT. This study examined the relationship between the post-SCT CRP levels and a leukemic relapse. Fifty-four consecutively transplanted patients who relapsed after the allogeneic SCT were compared with nonrelapsing patients. The serum CRP levels were measured on day 0 and every 7 days thereafter until 4 weeks after the SCT. The mean CRP levels throughout the early post-SCT episode were significantly lower in the relapsing patients than in those who did not experience relapse (mean+/-s.e.: 26.8 +/- 6.3 vs 65.3 +/- 9.4 for first week, P = 0.001; 23.9 +/- 3.8 vs 44.6 +/- 6.6 for second week, P = 0.008). Univariate analysis showed that the CRP level on the first and second week, and graft-versus-host disease were significantly associated with a relapse. Multivariate analysis showed that the CRP level on the first week was the strongest independent variable predicting the risk of a relapse after SCT (P = 0.04). These results indicate that the serum CRP levels early after allogeneic SCT might display the graft-versus-leukemia (GvL) effect. CRP is a surrogate of the proinflammatory cytokine release that was not measured in this study. The GvL effect appears to be efficiently strengthened by the high CRP levels that may be reflecting T-cell activation.

Adolescent↗

PubMed1997

Good correlation between RT-PCR analysis and relapse in Philadelphia (Ph1)-positive acute lymphoblastic leukemia (ALL).

We sequentially performed cytogenetic analysis and RT-PCR analysis of BCR-ABL transcripts in 17 cases of Ph1-positive ALL who had achieved hematological complete remission (CR) with intensive chemotherapy (CT). Sixteen cases were studied prospectively. All but one of the patients had reached cytogenetic CR, but cytogenetic has low sensitivity in predicting relapse. Twelve patients relapsed, three died in first CR and two were alive in first CR. Two of five, two of four, and five of nine patients who were allografted (in first or second CR), autografted and received consolidation CT, respectively, achieved negative two-round PCR in the bone marrow (BM): three died in CR, three remained in CR with negative two-step PCR in the BM and three relapsed after 22 to 28 months. In all cases, relapse was preceded by switch to PCR positivity in the BM by 4 to 6 months. The remaining nine patients remained PCR-positive in the BM and relapsed after 2 to 16 months. In the four autografted cases, PCR was positive at the time of bone marrow harvest. The two patients who received a purged transplant achieved negative PCR and prolonged CR, whereas the two patients who received an unpurged transplant remained PCR positive and relapsed. In 34% of the samples where analysis was concomitant, sensitivity of PCR proved lower in the blood than in the BM. These findings show that RT-PCR is a useful tool in the monitoring of MRD in Ph1 positive ALL.

Adult↗

PubMed1999

Clonal stability in children with acute lymphoblastic leukemia (ALL) who relapsed five or more years after diagnosis.

Although most relapses of childhood acute lymphoblastic leukemia (ALL) occur 24-36 months after first CR has been achieved, few patients relapse 5 or more years after CR achievement. The assessment of clonality has proved to be useful in determining whether even those very late events represent the reoccurrence of the original clone or alternatively a secondary leukemia. To gain further information on clonal stability in such late relapse, we performed detailed comparative Southern blotting and PCR analyses of TcRdelta and TcRgamma gene rearrangements in five ALL at presentation and subsequent relapse which occurred more than 5 years after diagnosis. At least one stable rearranged allele of the TcRdelta and TcRgamma loci was traced in all cases at presentation and clinical relapse despite a wide heterogeneity of the pattern of rearrangements. Our study extends to a larger series of patients previous findings which have sought to analyze the phenomenon of clonal evolution in children relapsed after more than 5 years of CCR. With respect to the potential pitfalls in monitoring minimal residual disease in childhood ALL for the presence of clonal evolution, our results highlight the combination of two target genes (such as TcRgamma and TcRdelta) as a tool to reduce false negative MRD results.

Blotting, Southern↗

PubMed2001

Quantification of minimal residual disease in children with oligoclonal B-precursor acute lymphoblastic leukemia indicates that the clones that grow out during relapse already have the slowest rate of reduction during induction therapy.

Antigen receptor gene rearrangements are applied for the PCR-based minimal residual disease (MRD) detection in acute lymphoblastic leukemia (ALL). It is known that ongoing rearrangements result in subclone formation, and that the relapsing subclone(s) can contain antigen receptor rearrangement(s) that differ from the rearrangements found in the major clone(s) at diagnosis. However, the mechanism leading to this so-called clonal evolution is not known, particularly at which time point in the disease the relapsing subclone obtains its (relative) therapy resistance. To obtain insight in clonal evolution, we followed the kinetics of several subclones in three oligoclonal ALL patients during induction therapy. Clone-specific nested PCR for immunoglobulin heavy chain or T cell receptor delta gene rearrangements were performed in limiting dilution assays on bone marrow samples taken at diagnosis, at the end of induction therapy and at possible relapse in three children with oligoclonal B-precursor ALL. We demonstrated that in all three patients the subclones were behaving differently in response to therapy. Moreover, in the two patients who relapsed, the clones that grew out during relapse showed the slowest regression or even evoluated during induction therapy and the clones that were not present at relapse showed good response to induction therapy. These results support the hypothesis that at least in some patients already at diagnosis or in the very first weeks, subclones have important differences in respect to resistance. Hence, these data give experimental evidence for the need to develop, during the first months after diagnosis, quantitative PCR assays for at least two different Ig/TCR gene rearrangement targets for every ALL patient.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation.

We have determined the predictive value of [18F]2-fluoro-2-deoxy-glucose (FDG-PET) in patients with Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) scheduled for high-dose therapy with stem cell transplantation (HDT/SCT). Inclusion criteria were the presence of an FDG-PET scan after chemotherapy (ChT) within 8 weeks prior to HDT/SCT and available follow-up data. Sixteen patients (10 NHL and six HD) were observed during a follow-up period of 4 to 28 months (median 13 months). Before SCT, five patients had a negative PET, three were weakly positive, two moderately positive, and six strongly positive. None of the five patients with a negative PET before HDT/SCT relapsed and two of three patients with a weakly positive scan are still in remission after HDT/SCT. Of eight patients with a moderate or high positive PET before HDT/SCT, seven relapsed and one died of early HDT/SCT related complications (P< 0.01). Three of eight relapsing patients died of lymphoma 5 to 10 months after SCT and in one additional patient not responding to HDT/SCT, the main cause of death was chronic toxicity 4 months after transplantation. After 12 months, in PET-negative patients the overall and relapse-free survival was 100%, in PET-positive patients 55% and 18%, respectively. In NHL, two patients with negative PET, but with an age-adjusted international prognostic index (AaIPI) of 2 and one with AaIPI = 1 are still in remission. In the seven PET-positive subjects, one patient with AaIPI = 0, three with AaIPI = 1, and two with AaIPI = 2 relapsed. We conclude that FDG-PET is accurate in the prediction of relapse prior to HDT/SCT in patients with lymphoma. It provides additional information when compared with the AaIPI.

Adult↗

PubMed2003

Clonality profile in relapsed precursor-B-ALL children by GeneScan and sequencing analyses. Consequences on minimal residual disease monitoring.

Detection of minimal residual disease (MRD), using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements as clone-specific targets, represents the most recent development in diagnosis and treatment of acute lymphoblastic leukaemia (ALL). Nevertheless, risk of false-negative results, due to secondary or ongoing rearrangements of Ig/TCR genes during the disease course, might hamper MRD detection. Therefore, to gain extensive information on clonal stability, we performed PCR-GeneScan analysis of Ig/TCR gene rearrangements at diagnosis and subsequent relapse in bone marrow samples from 53 childhood precursor-B-ALL patients. In addition, sequencing analysis of junctional regions at diagnosis and relapse provided a detailed insight in the stability and changes of Ig/TCR gene rearrangements during the disease course. At least one stable clonal Ig/TCR target was found in 94% of patients. In three patients complete differences in Ig/TCR rearrangements between diagnosis and relapse were observed, suggesting relapse with a new clone. At relapse, 71% of diagnostic clonal PCR targets was conserved. Since the comparison of Ig/TCR gene rearrangements at diagnosis and relapse in our precursor-B-ALL patients did not show significant difference in the stability of different clonal PCR targets (IGH, 70%; IGK, 71%; TCRD, 67%; TCRG, 75%), we conclude that there is no 'preferential' clone-specific target for MRD monitoring.

Adolescent↗

PubMed2003

Comparative analysis of T-cell receptor gene rearrangements at diagnosis and relapse of T-cell acute lymphoblastic leukemia (T-ALL) shows high stability of clonal markers for monitoring of minimal residual disease and reveals the occurrence of second T-ALL.

A total of 28 children and nine adults with relapsed T-ALL were analyzed for the configuration of their T-cell receptor (TCR) and TAL1 genes at diagnosis and relapse to evaluate their stability throughout the disease course. A total of 150 clonal TCR and TAL1 gene rearrangements were identified in the 37 patients at diagnosis. In 65% of cases all rearrangements and in 27% of cases most rearrangements found at diagnosis were preserved at relapse. Two children with unusually late T-ALL recurrences displayed completely different TCR gene rearrangement sequences between diagnosis and relapse. This indicates that a proportion of very late T-ALL recurrences might represent second T-ALL. Specifically, 88% of clonal rearrangements identified at diagnosis in truly relapsed T-ALL were preserved at relapse. This is significantly higher as compared to previously studied precursor-B-ALL ( approximately 70%). Thus, from biological point of view, immunogenotype of T-ALL is more stable as compared with precursor-B-ALL. The overall stability of TCR gene rearrangements was higher in adult T-ALL (97%) than in childhood T-ALL (86%). Based on the stability of TCR gene rearrangements, we propose a strategy for PCR target selection (TCRD+TAL1 --> TCRB --> TCRG), which probably allows reliable minimal residual disease detection in all T-ALL patients.

Adult↗

PubMed2004

Low-dose oral etoposide-based induction regimen for children with acute lymphoblastic leukemia in first bone marrow relapse.

We evaluated the clinical response to low-dose etoposide in relapsed acute lymphoblastic leukemia (ALL). Of the 45 patients with ALL in first bone marrow relapse enrolled on the ALL R15 protocol, 44 had received epipodophyllotoxins during frontline therapy. In the first week of remission induction therapy, patients received etoposide (50 mg/m(2) per day) administered orally as a single agent once or twice daily. On Day 8, patients started to receive dexamethasone, vincristine, and L-asparaginase. Etoposide was administered until Day 22. Two courses of consolidation therapy were followed by continuation therapy or hematopoietic stem cell transplantation. After 7 days of single-agent etoposide treatment, peripheral blast cell counts (P=0.013) and percentages of bone marrow blasts (P=0.016) were significantly reduced. In all, 38 (84.4%) attained second remission. Only time to relapse was significantly associated with outcome (P=0.025): the 5-year event-free survival estimates (+/-se) were 52.0+/-9.6% for those with late relapse and 20.0+/-8.0% for those with early relapse. We conclude that low-dose etoposide administered orally has a cytoreductive effect in relapsed ALL.

Administration, Oral↗

PubMed2006

Relapse of acute promyelocytic leukemia with PML-RARalpha mutant subclones independent of proximate all-trans retinoic acid selection pressure.

Relapse of acute promyelocytic leukemia (APL) following all-trans retinoic acid (ATRA) therapy has been associated with the acquisition of mutations in the high-affinity ATRA binding site in PML-RARalpha, but little information is available about the selection dynamics of the mutation-harboring subclones. In this study, 6/18 patients treated with sequential ATRA and chemotherapy on protocol INT0129 relapsed with complete replacement of the nonmutant pretreatment APL cell population by a PML-RARalpha mutant subclone. Two patients relapsed in proximity of ATRA treatment; however, in four patients there was a 6-48 month hiatus between the last ATRA treatment and relapse. The mutant subclones were not detectable in samples tested > or = 3 months before relapse at > or = 1 in 10(2) (10(-2)) sensitivity. In one patient, a functionally weak mutation was detected at 10(-4) sensitivity before therapy but only limited pre-relapse enrichment of the mutant subclone was observed on subsequent ATRA therapy. These results indicate that proximate ATRA selection pressure is frequently not the main determinant for the emergence of strongly dominant PML-RARalpha mutant subclones and suggest that APL subclones harboring PML-RARalpha mutations are predisposed to the acquisition of secondary genetic/epigenetic alterations that result in a growth/survival advantage.

Adult↗

PubMed1996

Symptomatic and endoscopic duodenal ulcer relapse rates 12 months following Helicobacter pylori eradication treatment with omeprazole and amoxycillin with or without metronidazole.

AIM: To determine the effect of Helicobacter pylori eradication with omeprazole and amoxycillin, with or without metronidazole, on the 12-month course of duodenal ulcer disease. METHODS: In a randomized; double-blind study, conducted in 19 hospitals, 105 H. pylori positive duodenal ulcer patients were healed and symptom-free following either omeprazole dual therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s., OA, eradication rate 46%, n = 52) or omeprazole triple therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s.+metronidazole 400 mg t.d.s., OAM, eradication rate 92%, n = 53) for 2 weeks, followed by 2 weeks of omeprazole 20 mg o.m. and a 12-month untreated follow-up period, after which time all patients were endoscoped. Endoscopic and symptomatic relapse rates, and effect on H. pylori status measured using 13C-urea breath test, were determined. RESULTS: During the 12-month untreated follow-up period, the life-table endoscopic relapse rates were 12% (95% CI: 2-22%) and 2% (95% CI: 0-6%) for OA and OAM patients, respectively. By 12 months, life-table symptomatic relapse rates were 22% (95% CI: 13-37%) and 19% (95% CI: 8-30%) for OA and OAM, respectively. In the 12 months untreated follow-up period, 2/69 (3%, 95% CI: 0-7%) patients rendered H. pylori negative had an endoscopic relapse at the end of the 12-month follow-up period, compared with 5/31 (16%, 95% CI: 3-29%) patients remaining H. pylori positive (P = 0.03 between H. pylori positive and negative groups). Twelve of 69 (17%, 95% CI: 8-26%) patients rendered H. pylori negative relapsed symptomatically, compared with 9/31 (29%, 95% CI: 13-45%) patients remaining H. pylori positive (P = N.S. between groups). There was a significant improvement in epigastric pain (P = 0.0001), nausea and vomiting (P < 0.05) between entry to the study and 1, 6 and 12 months post-treatment for both treatment groups. CONCLUSIONS: OAM eradicates H. pylori in significantly more patients than OA, but successful H. pylori eradication with either OAM or OA predisposes to low endoscopic and symptomatic relapse rates for duodenal ulcer patients when followed up for 12 months.

Adult↗

PubMed1999

Maintenance therapy with pantoprazole 20 mg prevents relapse of reflux oesophagitis.

BACKGROUND: Proton pump inhibitors can be effective as maintenance therapy in reducing the relapse rate of reflux oesophagitis at a dose lower than that used for acute healing. PATIENTS AND METHODS: Patients (n=396, 18-88 years old) with healed reflux oesophagitis (grade II or III before healing) were included in this multinational, prospective, parallel-group, randomized double-blind study. They took oral pantoprazole 20 mg (n=203) or 40 mg (n=193), once daily for up to 12 months. Scheduled endoscopies were performed at entry, after 6 and 12 months, or when symptoms of at least moderate intensity were perceived on 3 consecutive days; symptoms were assessed every 3 months. The primary efficacy parameter was the time until endoscopically proven relapse of reflux oesophagitis occurred; the secondary parameters included tolerability, safety and time until symptomatic relapse occurred. RESULTS: Analysis was performed using the 'all-patients-treated' approach. Endoscopic relapse rates in the 20 mg group after 6 and 12 months were 16 and 29%, respectively; in the 40 mg group, they were 7 and 19%, respectively. Symptomatic relapse rates after 6 and 12 months were 14 and 21% in the 20 mg group and 10 and 17% in the 40 mg group, respectively. Pantoprazole 20 mg and 40 mg were well tolerated throughout the study; the type and frequency of adverse events reported were similar for both treatment groups. CONCLUSION: The 20 mg dose was proven to be 'at least equivalent' to the 40 mg dose with respect to endoscopic and symptomatic relapse. The 20 mg once daily dose represents an effective and safe maintenance regimen for the majority of patients with healed reflux oesophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

Unrelated donor bone marrow transplantation for children with relapsed acute lymphoblastic leukaemia in second complete remission.

Allogeneic sibling bone marrow transplantation (BMT) is the recommended treatment for relapsed childhood acute lymphoblastic leukaemia (ALL), but appropriate donors are only available in 30% of cases. Unfortunately, BMT from unrelated donors (UD) has been associated with high rates of severe graft-versus-host disease (GvHD) and transplant-related mortality (TRM). In an attempt to improve outcome in UD-BMT we have assessed the impact of T-cell depletion using CAMPATH-1 (anti-CD52) monoclonal antibodies in 50 consecutively referred patients with relapsed ALL in second remission. All were previously treated according to MRC protocols UKALL X and XI, and then given chemotherapy on MRC R1 from relapse until UD-BMT, 19 patients had relapsed on and 31 off therapy. Patients and donors were fully matched at HLA-A, -B, -DR and -DQ loci in 29 cases and mismatched in 21 (four mismatched for more than one antigen). Pre-transplant conditioning comprised CAMPATH-1G, cyclophosphamide and total body irradiation. Bone marrow was T-cell depleted in vitro using CAMPATH-1 antibodies. Additional GvHD prophylaxis consisted of cyclosporin A (42 cases), cyclosporin plus methotrexate (four) or none (four). 47 patients engrafted. The incidence of acute GvHD was very low: two patients with grade II disease in the matched group, four with grade II-IV in the mismatched group. Only four patients have chronic GvHD. The actuarial event-free survival (EFS) at 2 years is 53%, with no significant difference between the matched and mismatched group. Further leukaemic relapse was the most important cause of failure. These results are similar to the most favourable published reports for HLA-matched sibling BMT in relapsed ALL.

Acute Disease↗

PubMed2000

Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Société Française de Greffe de moelle (SFGM).

Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T-cell-depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment occurred in 93% of cases, 32% of patients developed acute graft-vs.-host disease (GVHD) >/= grade II and 38% chronic GVHD. The 5-year overall and disease-free survival were 32 +/- 8% and 30 +/- 8%, respectively, with a risk of relapse of 44 +/- 12% and a transplant-related mortality of 45 +/- 9%. In a multivariate analysis, five factors were associated with a better outcome after 2nd SCT: age < 16 years at second transplant; relapse occurring more than 12 months after the first transplant; transplantation from a female donor; absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia in remission before transplant, in whom the HLA-identical donor was female and who relapsed more than 1 year after the first transplant.

Acute Disease↗

PubMed2000

Relapse of hirsutism following long-term successful treatment with oestrogen-progestogen combination.

OBJECTIVE: While several forms of treatment have been reported to be successful in relieving hirsutism over periods of 6-12 months, there is little if any information on the long-term outcome of hirsutism following the withdrawal of successful treatment. The combination of ethinyl oestradiol, 35 micrograms, and cyproterone acetate, 2 mg (EE-CA) for 21 days followed by 7 days without treatment is widely used in a cyclical manner in the treatment of hirsutism. The present study was undertaken to evaluate the outcome of withdrawal of long-term successful treatment of hirsutism with EE-CA. DESIGN, PATIENTS AND MEASUREMENT: In this retrospective study the clinical records of 57 patients with idiopathic hirsutism or polycystic ovary syndrome who had been treated with EE-CA were reviewed. The degree of hirsutism had been assessed by the Ferriman and Gallwey scoring system (FG). The testosterone/sex hormone binding globulin ratio (T/SHBG), was derived prior to and following the introduction of treatment with EE-CA. RESULTS: Fifty-two of the 57 patients achieved a satisfactory clinical response. In the group of patients who were satisfied with the outcome of treatment, FG decreased from 12.9 +/- 3.6 to 5.5 +/- 2.5 and T/SHBG ratio decreased from 11.3 +/- 9.5 to 1 +/- 0.8 (reference range: 1-5.2). The duration of treatment prior to its withdrawal in this group was 28.2 +/- 13.7 months. The five patients who were not satisfied with the response abandoned treatment after 16 +/- 2.8 months; the pretreatment FG was 16.2 +/- 8.3, while the T/SHBG decreased from 6.1 +/- 3.1 to 1.1 +/- 0.6 in these patients. Subsequent follow-up data, after withdrawal of treatment, were available on 34 of these 52 patients. Twenty-eight of the 34 patients exhibited relapse of hirsutism after 6.15 +/- 2.8 months. Six patients did not relapse during a follow-up period of 18.8 +/- 7. 8 months. The six patients who did not relapse were treated for a significantly longer period than the group who relapsed, 40 +/- 6.9 and 26.1 +/- 8.3 months, respectively, P < 0.01. However, the groups did not differ significantly when examined for pretreatment FG, 11.5 +/- 3.8 and 13.2 +/- 3.6 and pretreatment T/SHBG 8.9 +/- 5 and 13.4 +/- 11.9. CONCLUSION: These data indicate that ethinyl oestradiol and cyproterone acetate achieved a satisfactory clinical outcome in the treatment of hirsutism in 90% of patients. However, on withdrawal of treatment after a mean duration of over 2 years, relapse occurred in 80% of these patients after a mean of 6 months. If it is assumed that the successfully treated patients lost to follow-up all maintained long-term remission, the relapse rate is still an unsatisfactory 65% at 6 months. These are disappointing results which indicate for the first time that successful outcome requires that treatment be maintained for several years. Patients embarking upon treatment for hirsutism should be advised that maintenance of reduced hair growth requires long-term treatment, probably for at least 3-4 years.

Adult↗

PubMed2003

Prediction of relapse after interferon therapy in hepatitis C virus-infected patients by the use of triple assay.

BACKGROUND AND METHODS: In recent years, several tests have been used as predictive factors for relapse after the end of interferon therapy of chronic hepatitis C carriers. Serum hepatitis C virus (HCV)-RNA has proved insensitive for predicting relapse because more than 50% of patients with undetectable reverse transcription-polymerase chain reaction (RT-PCR) levels of HCV at the end of therapy become positive for viral RNA after interferon withdrawal. The detection of a minus RNA strand of HCV in liver also failed to efficiently predict relapses in chronic hepatitis patients. Furthermore, the use of a whole blood assay of HCV-RNA has been controversial. We used a triple assay comprised of RT-PCR tests for the detection of HCV-RNA plus strand in serum and peripheral blood mononuclear cells (PBMC), together with testing for the minus strand in PBMC for prediction of relapse after interferon + ribavirin combination therapy in 45 patients with chronic hepatitis C. RESULTS: The only four patients with a negative triple assay had no relapse 1 year after the end of therapy. In contrast, two-thirds of the 12 patients who tested negative for viral RNA in serum at the end of therapy relapsed 1 year later. CONCLUSION: We concluded that the absence of both minus and plus strands in patients who tested negative for serum PCR may indicate the total eradication of HCV.

Antiviral Agents↗

PubMed2000

Abdominal relapse in stage 1 nonseminomatous germ cell tumours of the testis managed by surveillance or with adjuvant chemotherapy.

OBJECTIVE: To assess the impact on patterns of recurrence of adjuvant chemotherapy in patients with stage 1 nonseminomatous germ cell tumours (NSGCT) of the testis, who have a high likelihood of relapse on surveillance if certain risk factors are identified in the orchidectomy specimen, and thus the theoretical need for retroperitoneal lymph node dissection (RPLND). PATIENTS AND METHODS: The incidence of abdominal relapse was recorded in 417 men presenting with stage 1 NSGCT over the past 18 years. Up to 1986, 161 men were managed by surveillance alone, and abdominal relapse occurred in 26. From 1986 onwards, men with positive risk factors in the orchidectomy specimen were offered two courses of chemotherapy; 60 accepted and one relapsed in the abdomen, and 196 underwent surveillance and 19 relapsed in the abdomen. RESULTS: Abdominal relapse was significantly reduced from 16% before 1986 to 8% afterward (P = 0.014). Mortality from testicular tumour or treatment toxicity remained low, at 0.6% before 1986 and 2.0% since then. CONCLUSION: The need for RPLND in stage 1 NSGCT remains highly doubtful.

Abdominal Neoplasms↗

PubMed1997

Serum CA125 assay at the time of relapse has no prognostic relevance in patients undergoing chemotherapy for recurrent ovarian cancer: a multicenter Italian study.

The present retrospective study assessed the prognostic value of serum CA125 assay at relapse in 73 patients with recurrent epithelial ovarian cancer. At the time of relapse, serum CA125 levels ranged from 7 to 7000 U ml-1. The 25%, 50% and 75% quantiles of CA125 levels were 76, 178 and 339 U ml-1, respectively. Antigen values were >35 U ml-1 in 67 (91.8%) of the 73 patients. Median time to recurrence was 16 months (range, 4-62 months). Serum CA125 levels at relapse were not related to site of recurrence, time to recurrence, FIGO stage, histologic type, tumor grade and residual disease after initial surgery. Sixty patients received salvage chemotherapy at relapse. In these patients survival after recurrence was significantly related to time to recurrence (< or = 6 months vs < 6 months, P = 0.0371; < or =12 months vs >12 months, P = 0.0014; < or =16 months vs >16 months, P = 0.0001), but not to CA125 level at relapse (at any cut-off value for the antigen: 35, 76, 178 and 339 U ml-1), site of recurrence, FIGO stage, histologic type, tumor grade and residual disease after initial surgery. In conclusion, time to recurrence was the only variable predictive of further survival in patients undergoing salvage chemotherapy for recurrent ovarian cancer, whereas serum CA125 level at relapse had no prognostic relevance.

Journal Article↗

PubMed2001

The role of disease stage in the response to donor lymphocyte infusions as treatment for leukemic relapse.

Between 1991 and 1999, 44 leukemic patients received donor lymphocyte infusions (DLIs) at our center (22 patients with chronic myelogenous leukemia [CML]; 10 with acute myelogenous leukemia; 11 with acute lymphatic leukemia; and 1 with myelodysplastic syndrome). Seventeen patients received graft-versus-host disease (GVHD) prophylaxis with methotrexate (MTX) at the time of DLI. In CML patients, 15 of 22 (68%) re-entered complete remission after DLI. At 3 years post-DLI, patients with cytogenetic (n = 10) or molecular (n = 3) relapse had a current leukemia-free survival (cLFS) rate of 85% compared with 0% for patients with hematologic relapse (P < .001). Among 15 CML patients who initially responded to DLI, 4 patients relapsed within the first 2 years. Four of 16 patients (25%) with acute leukemia had an initial response with complete remission after DLI. Two of them subsequently relapsed within 1 year. Patients with acute leukemia who relapsed within 1 year of hematopoietic stem cell transplantation (n = 9) had 0% cLFS at 18 months; patients with later relapse had 29% cLFS (P = .015). The overall probability of cLFS at 3 years for CML patients was 46%. For other diseases, cLFS was 13% at 18 months after DLI. Patients who developed chronic GVHD secondary to DLI showed a 3-year cLFS of 51% compared with 18% for patients without chronic GVHD (P = .022). This study emphasizes the importance of early disease stage and presence of chronic GVHD for effective DLI.

Adolescent↗