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PubMed1991

Improved treatment results in boys with overt testicular relapse during or shortly after initial therapy for acute lymphoblastic leukemia. A Pediatric Oncology group study.

Boys with acute lymphoblastic leukemia (ALL) who have overt testicular relapse (OTR) during initial continuation chemotherapy or within 6 months thereafter have poor outcomes, with long-term survival similar to patients with marrow relapse during treatment. In April 1983, the Pediatric Oncology Group (POG) adopted for these patients an intensive treatment protocol (POG 8303) consisting of a four-drug systemic reinduction (prednisone, vincristine, daunorubicin, and asparaginase), a brief intensive consolidation phase with teniposide and cytarabine, and a 2-year program of continuation chemotherapy with weekly rotating drug pairs (vincristine/cyclophosphamide and teniposide/cytarabine) with or without (by randomization) four-drug reinforcement pulses every 16 weeks. Bilateral testicular radiation (2600 cGy) was administered during reinduction, and intrathecal chemoprophylaxis was given every 4 to 6 weeks. Among 38 eligible study patients with OTR, 5 had prior or concominant extramedullary relapse in other sites. The median duration of complete remission before OTR was 27 months (range, 10 to 42 months). All 38 patients achieved clinical remission after reinduction. Three patients withdrew while in remission, 22 had another relapse (12 marrow, 5 central nervous system (CNS), 2 testicular, 1 retroperitoneal, 1 prostate, and 1 eye), and 13 (34%) remain in complete remission from 32+ to 74+ months after OTR (median, 53+ months). Eighteen patients had their therapy electively discontinued, and five relapses occurred thereafter. These results are superior to those observed in patients with first marrow relapse treated with the same protocol. Approximately one third of patients with OTR treated with POG protocol 8303 exhibit prolonged second remissions with the potential for cure.

Adolescent↗

PubMed1993

Time dependency of the influence of prognostic factors on relapse in breast cancer.

BACKGROUND: A number of factors concerning the prognosis of cancer patients have been reported, but the evaluation of individual factors is not always consistent. The author considered that the discrepancies may lie in part in that factors may have a changing influence on relapse with time. The present study was intended to reveal the phenomenon and its clinical significance in patients with breast cancer. METHODS: Eleven pathological prognostic factors in 462 patients with primary breast cancer were analysed with special reference to the influence on relapse and its changes with time. The Cox regression analysis was performed for whole and three stratified non-overlapping observation period (within 2, 2-5 and 5 years more), using factors including extent of nodal involvement (N), nuclear grade (NG), tumor infiltrating lymphocytes (TIL), tumor size, fat infiltration (F) and others. RESULTS: Cox regression analysis for whole observation period showed N followed by NG, TIL, F and others as the most important factors on relapse. But the analysis performed for 3 stratified intervals revealed that the influence on relapse decreased with time for N and NG, but tended to increase with time for F. The suppressive effect of TIL on relapse was not evident up to 2 years but was significantly emphasized after 2 years postoperatively. CONCLUSIONS: In conclusion, a distinct time-dependency with varied patterns was found in the influence of some prognostic factors on relapse, which implies the assessment of prognostic factors may vary according to the length of the observation period.

Adipose Tissue↗

PubMed2002

Interferon for interferon nonresponding and relapsing patients with chronic hepatitis C.

BACKGROUND: Interferon monotherapy leads to sustained virologic clearance in a minority of patients with chronic hepatitis C. Studies have yielded conflicting results regarding retreatment with interferon in nonresponders and relapsers. OBJECTIVES: To assess the beneficial and harmful effects of retreatment with interferon in chronic hepatitis C nonresponders and relapsers to previous interferon treatment. SEARCH STRATEGY: Trials were identified through electronic databases, manual searches, authors, and pharmaceutical companies (August 2001). SELECTION CRITERIA: Randomised trials comparing interferon versus control or different interferon regimens in chronic hepatitis C patients being nonresponders and relapsers to previous interferon were included. DATA COLLECTION AND ANALYSIS: The primary outcome was failure to achieve a sustained virologic response defined as positive serum hepatitis C virus RNA at least six months following treatment. Secondary outcomes included liver-related morbidity, mortality, biochemical responses, adverse events, and histology. MAIN RESULTS: Ten randomised trials involving 686 nonresponders and eight trials involving 484 relapsers were included; their methodological quality was poor. In nonresponders, interferon reduced the risk of not achieving an end of treatment biochemical response compared with no treatment (relative risk [RR] 0.77, 95% confidence interval [CI] 0.66 to 0.91); however, virologic responses were not reported. In a post hoc subgroup analysis, doses greater than 3 million units (MU) three times weekly offered no advantage compared with 3 MU three times weekly for biochemical sustained response. Failure to obtain a virologic sustained response was less likely with 48 than 24 weeks of therapy (RR 0.87, 95% CI 0.79 to 0.96). Adverse events did not differ significantly regardless of treatment dose or duration. In relapsers, none of the trials compared interferon with no treatment. In a post hoc analysis, doses greater than 3 MU three times weekly were no more effective in achieving a virologic sustained response than 3 MU three times weekly. Compared with 24 weeks, treatment durations of 48 weeks were less likely to fail to achieve a virologic sustained response (RR 0.69, 95% CI Random 0.51 to 0.95), but associated with more frequent dosage reduction (RR 9.07, 95% CI 1.20 to 68.63). No data regarding clinical outcomes or histology was available in either patient group. REVIEWER'S CONCLUSIONS: Retreatment with interferon leads to sustained virologic clearance in a minority of chronic hepatitis C patients with nonresponse or relapse following interferon monotherapy. Treatment durations of 48 weeks are superior to 24 weeks, but doses greater than 3 MU three times weekly are no more effective. No data exists regarding the effect on clinical outcomes.

Antiviral Agents↗

PubMed2000

Prediction of relapses in Wegener's granulomatosis by measurement of antineutrophil cytoplasmic antibody levels: a prospective study.

OBJECTIVE: Prediction of relapses in Wegener's granulomatosis (WG) by measuring levels of antineutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) or myeloperoxidase (MPO) remains a controversial issue. To assess the value of serial quantification of ANCA by indirect immunofluorescence (IIF) and antigen-specific enzyme-linked immunosorbent assay (ELISA) for monitoring disease activity in patients with WG, a prospective observational study was conducted in patients with WG attending an outpatient clinic in the Netherlands. METHODS: One hundred patients with WG (85 with PR3-ANCA, 15 with MPO-ANCA) were studied prospectively from 1996 to 1998. Serum samples were obtained and analyzed every 2 months for ANCA levels. Disease activity was prospectively assessed without knowledge of the ANCA levels. RESULTS: Relapses occurred in 37 of 100 patients (37%). Thirty-four (92%) of the 37 patients showed a rise in the level of ANCA preceding their relapse, as detected by ELISA or IIF. The predictive value of an increase in ANCA titers for relapse was 57% (17 of 30) for cytoplasmic/classic ANCA (cANCA; by IIF), 71% (27 of 38) for PR3-ANCA (by ELISA), and 100% (3 of 3) for MPO-ANCA (by ELISA). The predictive value of a rise in ANCA as measured by ELISA or IIF did not substantially improve following concomitant measurement of the IgG3 subclass of PR3-ANCA. Forty-three percent of patients who showed a rise in cANCA (by IIF) and 29% with a rise in PR3-ANCA (by ELISA) did not subsequently experience a relapse. CONCLUSION: Serial measurement of ANCA levels is valuable for the early prediction of relapses in patients with WG.

Adult↗

PubMed2002

Detection of relapse in non-Hodgkin's lymphoma: role of routine follow-up studies.

Complete remission can be achieved in 60-80% of adults with diffuse aggressive non-Hodgkin's lymphoma. However, 20-40% of them will subsequently relapse. Nevertheless, formal follow-up guidelines for recurrence detection have never been advocated. We analyzed the pattern of relapse in 30 patients with intermediate- and high-grade non-Hodgkin's lymphoma and the value of intensive protocol for relapse detection. This protocol includes frequent follow-up visits, complete blood count, and serum LDH tests along with annual chest, abdominal, and pelvic CT scans. The median duration of complete remission was 12 months. Twenty-five relapses (83%) were suspected after an interim history and/or physical examination, whereas only 5 relapses (17%) were detected by routine radiographic or laboratory follow-up studies. The majority of relapses (19/30) were detected in sites that included the sites of prior disease. For the first 12 months of complete remission, the estimated cumulative save in charge for a follow-up strategy, based on regular visits in the hematology clinic and performing laboratory and radiologic studies as clinically indicated, is 44% of the cost of a routine intensive evaluation. A reliable and cost-effective follow-up method for non-Hodgkin's lymphoma patients in complete remission should include frequent history and physical examination. Complementary studies should be performed according to clinical indications.

Aged↗

PubMed1981

Late relapses in Hodgkin disease.

Among a cohort of 142 patients with Hodgkin disease (HD), pathologic stages (PS) IA through IVB, 84 remained in complete remission (CR) at least 3 years after the completion of initial protocol therapy. Eight of these patients subsequently developed a recurrence of HD and were defined as having a late relapse. The disease-free interval ranged from 37 to 76 months (median 53 months). Six of the relapse patterns were those of dissemination. All patients were salvaged and are in CR from 14 to 50 months after relapse. The actuarial survival, measured from the time of relapse, of the eight late-relapsing patients was superior to the actuarial survival of 38 patients with early relapse (disease-free interval less than 36 months), but as yet this difference is not statistically significant (P = 0.07, Gehan).

Adult↗

PubMed1985

Adoptive transfer of murine relapsing experimental allergic encephalomyelitis.

Relapsing experimental allergic encephalomyelitis (EAE), an autoimmune disorder resembling multiple sclerosis, has been produced by inoculating SJL/J mice with spinal cord or myelin basic protein in appropriate adjuvants. To determine whether initially sensitized lymphocytes or the persistence of antigen depots in the animal were responsible for the relapsing episodes of inflammatory demyelination, adoptive transfer studies were undertaken utilizing lymphocytes from relapsing EAE-immunized donors transferred directly or after in vitro culture. In direct-transfer studies donor lymphocytes produced clinical and pathological signs of relapsing EAE in 3 of 7 recipients of lymph node lymphocytes and 1 of 5 recipients of splenic lymphocytes. In vitro culture of lymphocytes in myelin basic protein or T cell growth factor prior to transfer increased both the incidence of disease and the number of animals having relapses, and allowed transfer with fewer lymphocytes. Because all animals had delayed onset of disease, this study demonstrates that the ability to develop relapsing inflammatory demyelination is transferable with lymphocytes and does not require the presence of antigen.

Animals↗

PubMed2004

Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: who benefits?

BACKGROUND: This study was performed to address patient selection criteria and the role of secondary cytoreductive surgery (SCR) in patients with epithelial ovarian carcinoma (EOC) who had relapsed tumors after a progression-free interval > or = 3 months. METHODS: One hundred seventeen patients with relapsed EOC after a clinical complete remission duration > or = 3 months who underwent SCR were entered on this prospective trial. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using log-rank tests, logistic stepwise regression analyses, and a Cox stepwise regression model. RESULTS: The median patient age at the time of relapse was 53 years (range, 20-78 years). The median survival was 22 months and the estimated 5-year survival rate for the entire cohort was 17.2%. Tumor was confined to a solitary site in 33 patients and to > or = 2 sites in 84 patients. After they underwent SCR, 11 patients were rendered macroscopically disease free, 61 patients had residual disease that measured < or = 1 cm in greatest dimension, and 45 patients had bulky intraabdominal residual disease. Survival was influenced by the extent of relapse disease (solitary site vs. multiple sites; P < 0.0001), the size of residual disease after SCR (0 cm vs. < or = 1 cm [P = 0.1211], < or = 1 cm vs. > 1 cm [P = 0.0002], and 0 cm vs. > 1 cm [P = 0.0011]), Eastern Cooperative Oncology Group performance status (0 vs. 1 [P = 0.134], 1 vs. 2 [P = 0.007], and 0 vs. 2 [P = 0.0012]), and the number of cycles of salvage chemotherapy (1-2 cycles vs. 3-5 cycles [P = 0.0144]; 1-2 cycles vs. > or = 6 cycles [P < 0.0001]; and 3-5 cycles vs. > or = 6 cycles [P = 0.0009]). The outcome of SCR was influenced by the extent of relapse disease (multiple sites [51.2%] vs. solitary sites [87.9%]; relative risk [RR] = 9.1237; P = 0.0002) and by the use of bowel resection (yes [60.9%] vs. no [37.5%]; RR = 0.3828; P = 0.0106). CONCLUSIONS: SCR was found to be safe for patients with relapsed EOC who achieved a clinical complete remission that lasted > or = 3 months, with resectability similar to that of primary debulking surgery. Optimal surgical outcomes were achieved easily in patients who apparently had solitary tumor sites, with bowel resection making it possible to remove bulky tumors that involved the intestine. A survival benefit was provided by optimal SCR, particularly when surgery was supported by multiple courses of salvage chemotherapy.

Adult↗

PubMed2005

Comparison of diagnostic and relapse flow cytometry phenotypes in childhood acute lymphoblastic leukemia: implications for residual disease detection: a report from the children's oncology group.

BACKGROUND: Flow cytometric analysis of minimal residual disease (MRD) depends on detecting phenotypically abnormal populations. However, little is known about how phenotypic shifts between diagnosis and relapse affect MRD detection in childhood acute lymphoid leukemia (ALL). METHODS: We compared diagnostic and relapse bone marrow specimens in 42 children with precursor B-ALL studied with the two-tube panel CD19-APC/CD45-PerCP/CD10-PE/CD20-FITC and CD19-APC/CD45-PerCP/CD9-PE/CD34-FITC. RESULTS: At least 29 cases had phenotypic shifts of intensity or coefficient of variation of distribution of one or more markers. Shifts were complex and could not be explained by change in maturation stage. In the majority of cases MRD populations more closely resembled the diagnostic than the relapse specimen. In 6 of 7 MRD negative cases we did not identify an abnormal population that resembled diagnosis or relapse. In the remaining case, in which CD34 and CD10 were lost between diagnosis and relapse, it is possible that we could have missed an MRD population resembling relapse. CONCLUSIONS: Phenotypic shifts are common, but do not affect MRD recognition. At most 1 of 42 cases might have harbored an abnormal population undetected because of shift. However, MRD analysis with rigid gating (looking strictly for abnormal phenotypes at diagnosis) might have missed many positive cases, 8 of 22 (36%) in this series.

Child↗

PubMed1997

Relapsing and remitting experimental allergic encephalomyelitis: a focused response to the encephalitogenic peptide rather than epitope spread.

The progression of experimental allergic encephalomyelitis (EAE) in certain mouse strains has been reported to involve a broadening of the response to myelin antigens, apparently resulting from priming to endogenous determinants of the myelin sheath. The phenomenon has been termed determinant spread. Interest in this effect has centered on the mechanism it offers to explain the progressive, relapsing and remitting course of EAE and indeed of multiple sclerosis. We have conducted a systematic, longitudinal study in SJL mice to look for determinant spread during relapsing and remitting EAE, correlating epitope recognition and cytokine production with disease severity. Disease was induced using three of the four encephalitogenic proteolipid protein or myelin basic protein epitopes, and responses to each of four epitopes recognized by SJL T cells were tracked through acute disease, remission and relapse. The responses of lymph node cells, splenocytes and central nervous system (CNS)-infiltrating T cells were analyzed. While marginal, transient responses to secondary epitopes were detectable in splenocytes, CNS-infiltrating cells showed a dominant response to the original disease-inducing epitope without evidence of a shift to other determinants during relapse. Disease relapse was correlated with an increase in CNS-infiltrating cells and a high proliferative and interferon (IFN)-gamma response to the disease-inducing peptide. During remission, there was a decrease in numbers of cells infiltrating the CNS. These cells were down-regulated, showing low if any response to the myelin peptides tested as measured by proliferation, production of IFN-gamma or production of IL-4. Our findings argue strongly against a causal role for determinant spread in disease relapse as observed in these models of EAE.

Amino Acid Sequence↗

PubMed2005

ETV6/RUNX1 fusion at diagnosis and relapse: some prognostic indications.

This study was undertaken in order to compare the interphase and metaphase cytogenetics of 28 patients with ETV6/RUNX1 positive acute lymphoblastic leukemia, at diagnosis and relapse. The median time to relapse was 26 months. The significant fusion positive population heterogeneity revealed at interphase by a commercial probe for ETV6/RUNX1 fusion has not been described before. Six diagnostic samples had a single abnormal population; others had up to five each, which differed in the numbers of RUNX1 signals, and in the retention or loss of the second ETV6 signal. In contrast, the number of fusion signals was more constant. At relapse, there were fewer populations; the largest or unique clone was sometimes a re-emergence of a minor, diagnostic one, with a retained copy of ETV6 and the most RUNX1 signals. Abnormal, fusion negative clones were identified in bone marrow samples at extra-medullary relapse. Variant three or four-way translocations, which involved chromosomes 12 and 21, were prominent among the complex rearrangements revealed by metaphase FISH. The frequency of their occurrence at diagnosis and reappearance at relapse, sometimes accompanied by minor clonal evolution, was another new observation. Other recurrent cytogenetic features included a second copy of the fusion signal in six cases, partial duplication of the long arm of the X chromosome in two cases, and trisomy 10 in three cases. In comparing our data with previously reported cases, a picture is beginning to emerge of certain diagnostic features, which may provide circumstantial evidence of an increased risk of relapse.

Adolescent↗

PubMed1994

Phagocytic activity of macrophages and microglial cells during the course of acute and chronic relapsing experimental autoimmune encephalomyelitis.

The ED1 monoclonal antibody recognizes an antigen in lysosomal membranes of phagocytes. The expression of this antigen in cells increases during phagocytic activity. Here we describe the expression of ED1-immunoreactivity during the various stages of both acute (monophasic) and chronic relapsing experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. During the first attack of acute and chronic relapsing EAE, ED1-immunoreactivity was present in macrophages and in cells which displayed morphologic features of activated microglial cells (i.e., cells with thick short processes). At the ultrastructural level these cells were seen to contain phagocytosed myelin structures in lysosomes. ED1-immunoreactivity in these cells was present in the cytoplasm near lysosomes. During the remission phase of acute EAE and the relapse phase of chronic relapsing EAE, ED1-positive cells with dendritic morphology not only were present in or nearby lesions, but were also found at sites distant from lesions throughout large parts of the brain. These cells had a morphology comparable to microglial cells in normal brain. A major difference between animals which were in remission and animals which on day 25 were suffering from a relapse, was that the latter showed the presence of lesions with darkly stained round ED1-positive macrophages and activated microglial cells. These results indicate that during a relapse, newly recruited blood-borne macrophages infiltrate the brain and, together with activated lymphocytes and microglial cells, recommence a new demyelination process.

Acute Disease↗

PubMed1979

Relapse rates following cessation of chemotherapy during complete remission of acute lymphocytic leukemia.

The therapeutic benefit of maintenance chemotherapy beyond three years for children with acute lymphocytic leukemia (ALL) in continuous complete remission was evaluated by the investigators of Childrens Cancer Study Group (CCSG). Two hundred and twenty leukemic children in first remission for three years or longer and who had received at least three years of continuous chemotherapy were eligible. One hundred and one patients were randomized to either continue chemotherapy for an additional three years or to discontinue therapy, and 119 patients nonrandomly continued or discontinued therapy. The patients had received a variety of chemotherapy regimens. The study period extended from April 1970 until December 1977, with a median follow-up time of 25 months. Relapses occurred in 15 randomized patients (15%). Randomized patients remaining on chemotherapy experienced a statistically significant lower relapse rate than patients randomized to discontinue therapy. Also among randomized patients, bone marrow relapse was significantly more frequent in males than in females. Considering the total patient group, age and white blood count at diagnosis had no significance in predicting relapse. Of relapse events in males, 21% were isolated testicular relapses, identifying the testicles as a major risk site in males completing three years of continuous complete remission. This study demonstrates that continuing chemotherapy beyond three years results in a significant prolongation of remission in males, although the eventual survival outcome for later discontinuance of therapy will require longer follow-up.

Bone Neoplasms↗

PubMed1985

Marrow transplant experience in children with acute lymphoblastic leukemia: an analysis of factors associated with survival, relapse, and graft-versus-host disease.

One hundred fourteen children with acute lymphoblastic leukemia were treated with allogeneic marrow transplantation from HLA-identical siblings after conditioning with cyclophosphamide and total body irradiation. Methotrexate was given posttransplantation for prophylaxis of graft-versus-host disease. The minimum follow-up after transplantation was 2 years. Sixteen of 51 patients transplanted in marrow remission survive from 2.1 to 8.9 years (median 2.7), 13 in continuous remission, one in remission following testicular relapse, and two after marrow relapse. Sixty-three were transplanted in relapse and eight survived 3-10 years (median 5.7), five in continuous remission, and three in remission following testicular relapse. In a multivariate analysis, factors significantly related to increased survival were marrow remission at transplant (p less than 0.007) and chronic graft-versus-host disease (p less than 0.005). Factors associated with increased relapse were marrow relapse at transplant (p less than 0.002) and absence of significant graft-versus-host disease (p less than 0.004). The development of acute graft-versus-host disease was associated with high marrow cell doses (p less than 0.04). These data suggest that some children with acute lymphoblastic leukemia and a poor prognosis with conventional chemotherapy may be cured with marrow transplantation.

Adolescent↗

PubMed1993

Superior prognosis in combined compared to isolated bone marrow relapses in salvage therapy of childhood acute lymphoblastic leukemia.

Three hundred twenty-six children with bone marrow (BM) relapse of non-B acute lymphoblastic leukemia (ALL) were stratified according to the time of relapse in three consecutive multicenter trials--ALL-REZ BFM 83, 85, and 87. Employing an intensive polychemotherapy regimen, extramedullary involvement appeared to be predictive of superior outcome in both strata as well as in the whole group (probability of 7-year event-free survival (EFS) 42% in combined vs. 15% in isolated BM relapse, P = 0.015). Children with combined BM relapse occurring later than 6 months after completion of front-line therapy reached EFS estimates of 60%. We conclude that results of conventional polychemotherapy with BFM relapse protocols are equivalent to those achieved by bone marrow transplantation in children with late combined BM relapse.

Adolescent↗

PubMed2005

Outcome of children with primary resistant or relapsed non-Hodgkin lymphoma and mature B-cell leukemia after intensive first-line treatment: a population-based analysis of the Austrian Cooperative Study Group.

BACKGROUND: Children and adolescents with Non-Hodgkin lymphoma (NHL) and mature B-cell leukemia (B-ALL) have an excellent prognosis with contemporary chemotherapy stratified according to the histologic subtype and clinical stage of disease. However, a small subset of patients does not respond to front-line therapy or suffers from an early relapse. PROCEDURE: A retrospective analysis was performed to assess the incidence, treatment, and outcome of all children with relapsed or progressed NHL and B-ALL diagnosed in Austria between 1986 and 2003 (n = 22/234). RESULTS: Nine of 140 (6.5%) patients with B-cell NHL/B-ALL (relapse, n = 6; progress, n = 3) failed initial treatment. Four of them underwent a hematopoietic stem cell transplantation (HSCT) as second-line therapy, two patients received intensive chemotherapy alone and in three patients treatment was palliative. Eight of the nine patients died of their disease. Four of 65 (6%) patients with lymphoblastic lymphoma (LBL) (relapse, n = 2; progress, n = 2) had a treatment failure. High-dose chemotherapy followed by HSCT was performed in two of the four patients; another two patients received chemotherapy alone. Three of the four patients died of resistant disease. Nine of 29 (31%) patients with anaplastic large cell lymphoma (ALCL) (relapse, n = 7; progress, n = 2) failed first-line therapy. Six underwent a HSCT (autologous, n = 3; allogeneic, n = 3) and are currently in second complete remission. Treatment of the other three patients consisted of chemotherapy alone-they all died of tumor progression. CONCLUSIONS: Conclusively, patients with early relapsed and progressive B-cell neoplasia or LBL have a very poor prognosis with current treatment approaches, while those with ALCL have a respectable chance to achieve a sustained complete second remission with high-dose chemotherapy and HSCT.

Adolescent↗

PubMed2006

Survival after relapse in children with solid tumors: a follow-up study from the Italian off-therapy registry.

BACKGROUND: Despite the increased survival of children with solid tumors, a significant proportion of cases still relapse following treatment discontinuation, and knowledge about the long-term outcome of this selected group of patients remains incomplete. OBJECTIVE: To describe the long-term outcome of children treated for a solid tumor who relapsed after the elective end of therapy, and to explore factors associated with survival. METHODS: All patients with the selected diagnoses-Hodgkin disease (HD), neuroblastoma (NB), tumor of the central nervous system (CNS), Wilms tumor (WT), or soft tissue sarcoma (STS)-enrolled in the Italian Pediatric Off-Therapy Registry in the period 1980-1998 were evaluated. Out of 3,927 patients, 694 had relapsed after treatment suspension; 639 were available for analysis. Survival and event-free survival were estimated by the Kaplan-Meier method. The log-rank test was used to assess differences in survival among the various types of cancer considered. Multivariate Cox proportional hazards analysis was adopted to explore possible prognostic factors. RESULTS: There were 335 deaths: most of them (93%) were related to the primary cancer. The overall survival rate after relapse was 38% (95% CI 33-42) at 5 years, and 32% (95% CI 27-36%) at 15 years, while event free survival was 31% (95% CI 26-35) and 26% (95% CI 22-30%), respectively. There were significant differences according to the original diagnosis, with patients with HD doing better, and those with NB, CNS, and STS worse. No improvement of prognosis was evident over time. Post-relapse stem cell transplantation was associated with decreased risk of death only in the first year, not thereafter. CONCLUSIONS: Overall, patients with solid tumors who relapse after treatment discontinuation have a poor outcome, but significant differences exist according to the tumor types.

Adolescent↗

PubMed2007

Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma.

OBJECTIVE: To assess the outcome and determine risk factors for extraocular relapse in patients with retinoblastoma who had been enucleated after failure of chemoreduction. METHODS: Retrospective study (1995-2002) at three institutions. Pathological risk factors (PRF) were defined as invasion of the anterior segment, choroid, post-laminar optic nerve, subarachnoid space, or sclera according to the local pathology report. Extraocular relapse was defined as an event. RESULTS: One hundred twenty-two patients were included (17 had bilateral enucleation). Chemoreduction included vincristine, carboplatin, and etoposide (n=80, 65.6%), vincristine, and carboplatin (n=17, 13.9%), or carboplatin (n=25, 20.5%). Thirty-five also received external beam radiotherapy (28.7%). PRF included: 39 with choroidal involvement, 9 with anterior segment, 9 with scleral, and 2 with post-laminar optic nerve with subarachnoid invasion. Adjuvant chemotherapy was given to eight patients (6.5%) because of scleral invasion. Four patients had an extraocular relapse after enucleation, two of whom survive after intensive treatment including stem cell rescue. Five-year probability of event-free survival is 0.96. Only scleral invasion and bilateral enucleation were significantly associated with extraocular relapse. CONCLUSIONS: The risk of extraocular relapse is low after enucleation following failure of chemoreduction. Patients who underwent bilateral enucleation and those with scleral invasion are at higher risk of extraocular relapse.

Antineoplastic Agents↗