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PubMedDate not supplied

Improvement of prognosis in refractory and relapsed acute promyelocytic leukemia over recent years: the role of all-trans retinoic acid therapy.

With the aim of determining the ability of all-trans retinoic acid (ATRA) to improve prognosis in refractory and relapsed acute promyelocytic leukemia (APL), the data of 45 patients resistant to previous conventional chemotherapy or in first relapse were retrospectively reviewed. Thirty-seven patients presented with typical M3, five with variant form (M3v), and three with intermediate form. Seven patients died before any chemotherapy could be given. Thirty-five patients received one course of chemotherapy combining anthracyclines and cytarabine without (n = 22) or with ATRA (n = 13), according to different protocols. One elderly patient received only ATRA, and two patients received only low-dose cytarabine. Nine patients died within 4 weeks of relapse. A complete remission (CR) was achieved in 29 of the 38 patients retreated after first relapse or primary failure (76.3%, 95% CI: 60-89%). Among relapsed patients, four of five patients who had initially received ATRA therapy achieved a second CR when retreated by ATRA. The median second disease-free survival (DFS) was 23.3 months. Overall median survival was 7.8 months, with a 5-year survival rate of 29% (95% CI: 14-44%). Parameters found to be associated with decreased second CR rate were presence of hemorrhages and hemostatic disorder, and high levels of GGT at the time of relapse. Factors associated with short survival were WHO performance status > 1, high serum LDH levels, and coagulopathy at time of relapse. Use of ATRA at time of relapse (n = 14) was significantly associated with higher CR rates (p = 0.008), longer DFS (median not reached versus 7.9 months; p = 0.05), and longer survival after first relapse (median 32.3 months versus 4.4 months; p = 0.003). In the multivariate analysis, the only factor predictive of poor prognosis for overall survival was the absence of ATRA therapy at relapse. We conclude that ATRA is effective in the treatment of relapsed or refractory APL and appears superior to chemotherapy alone.

Adult↗

PubMed2000

Increased response rate to interferon therapy after a second course in hepatitis C patients who show relapse after the initial course.

Some patients with chronic hepatitis C become HCV-RNA seronegative during interferon (IFN) therapy. However, about one-half of these patients show a relapse, evident by high serum alanine aminotransferase (ALT) level. In some patients with biochemical relapse, the serum HCV-RNA level becomes low immediately after the ALT relapse. Here, we assessed the changes in serum HCV-RNA level in patients with ALT relapse after IFN therapy, and evaluated the efficacy of a second course of IFN, started at the recovery stage after ALT relapse. Two hundred and seventy-seven patients who showed HCV-RNA seronegativity by reverse transcription nested-polymerase chain reaction (RT nested-PCR) and normalization of ALT during the initial IFN therapy, and had positive HCV-RNA with ALT relapse (> 100 IU/l) within 3 months after completion of the initial IFN course were enrolled in this retrospective study. Two hundred and sixty patients were followed-up without further IFN retreatment after the ALT relapse (group 1), and 17 patients received another 6-month course of IFN after the ALT relapse (group 2). The median level of serum HCV-RNA, determined with a branched DNA probe assay (version 1; Chiron-Dai-ichi Kagaku Tokyo, Japan), in group 1 was 3.1 Meq/ml before IFN therapy, 1.3 Meq/ml at the time point of the ALT peak after the completion of IFN therapy, and 0.7 and 2.6 Meq/ml at 2-4 and 6-8 weeks after the ALT peak, respectively. The serum HCV-RNA level at 2-4 weeks after the ALT peak was lower than that before IFN therapy. The eradication rate of HCV-RNA (complete response; CR) in group 2 (47.1%; 8/17) was significantly higher than that in group 1 (1.5%; 4/260; P < 0.001). In conclusion, our data suggested that: (1) patients who showed biochemical relapse after initial IFN therapy had a significantly lower serum HCV-RNA level at recovery after ALT relapse compared with that before initial IFN therapy. (2) A high response rate was noted after a second course of IFN administered at the recovery stage of the ALT relapse, compared with patients without IFN retreatment.

Adult↗

PubMedDate not supplied

Relapse precipitants and behavioral marital therapy.

The major purpose of this study was to provide descriptive data on the first relapse episodes and reasons for terminating relapses of subjects who completed a course of behavioral marital therapy (BMT) for alcoholism. Another aim of the study was to compare the relapse episodes and relapse terminations of subjects who received BMT with or without additional relapse prevention (RP) treatment for one year. The subjects were selected from a sample of 74 men who began an outpatient Department of Veterans Affairs BMT program. These men were evaluated pre- and post-BMT, and at 3, 6, 9, and 12 months after completing BMT. A total of 31 subjects relapsed at least once after they began BMT. The data showed that these men tended to report more than one situational or personal precipitant of their first relapses. Similarly, they tended to report more than one reason for ending their relapse episodes. Comparison of the subjects assigned to the two RP conditions revealed an equal number (12) of relapse episodes, but RP subjects' relapses tended to last fewer days than did no-RP subjects'. The consistency of these findings with previous research on cognitive-behavioral models of relapse and the implications of these findings for the concept of high-risk situation, are discussed.

Adult↗

PubMed1995

Survival outcome following isolated central nervous system relapse treated with additional chemotherapy and craniospinal irradiation in childhood acute lymphoblastic leukemia.

PURPOSE: An analysis of survival outcome following isolated central nervous system (CNS) relapse treated with craniospinal irradiation (CSI) and additional chemotherapy in children with acute lymphoblastic leukemia (ALL) was conducted. METHODS AND MATERIALS: Eighteen of 344 pediatric patients with ALL who attained initial complete remission on the St. Jude Children's Research Hospital "Study XI" prospective protocol (1984-1988) developed a CNS relapse as first adverse event. Median interval to isolated CNS relapse was 7.5 months (range = 2-40 months) after achieving initial complete remission. At diagnosis, 14 of the 18 children were categorized as "high risk" for subsequent leukemic relapse. Preventive cranial irradiation [PCI (18 Gy)] was delivered as planned to one of the 14 "high-risk" children. The other 13 "high-risk" patients experienced a CNS relapse during the first year of continuation therapy prior to week 52 of planned PCI. All four "low-risk" patients experienced a CNS relapse beyond the first year of continuation therapy; none were scheduled to receive PCI. Following isolated CNS relapse, all 18 patients were treated on a prospective contingency of "Study XI" trial consisting of intensified reinduction chemotherapy, weekly intrathecal methotrexate/hydrocortisone/Ara-C x 4-6 injections, craniospinal irradiation (cranium to 24.0 Gy and spine to 15.0 Gy at 1.5 Gy/fraction) and maintenance systemic therapy for a minimum of 1 year. RESULTS: Ten of 18 patients remain in continuous complete secondary remission at 17 to 50 months post-CNS relapse. Second sites of relapse in the remaining eight children were as follows: CNS in four, bone marrow in three, and bilateral testicular in one patient. Each of these eight patients died of progressive leukemia. At a median followup of 40 months post-initial CNS relapse, the 3-year secondary Kaplan-Meier survival and event-free survival are 72% and 56%, respectively. Minimal long-term neurotoxicity was associated with the treatment regimen. The most important prognostic factors predicting continuous secondary remission included white blood cell count at diagnosis (p = 0.05), and duration of initial remission (p = 0.04). CONCLUSION: This trial demonstrates that more than one-half of patients may be successfully salvaged with intensified chemotherapy and craniospinal irradiation without significant morbidity following an isolated CNS relapse, despite previous multiagent chemotherapy though virtually no prior PCI in childhood ALL.

Adolescent↗

PubMed1995

Radiation therapy for chordomas of the base of skull and cervical spine: patterns of failure and outcome after relapse.

PURPOSE: To determine the patterns of failure and outcome following relapse of chordomas of the base of skull and cervical spine. METHODS AND MATERIALS: Between November 1975 and October 1993, 204 patients were treated for chordoma of the base of skull or cervical spine, of which 63 have developed relapse. These 63 patients constitute the main focus of this study. Forty-five patients presented with base of skull and 18 with cervical spine tumors. All patients received combined proton and photon beam radiation. The median prescribed dose was 70.1 cobalt-Gray equivalent (CGE) (range 66.6-77.4). There were 25 males and 38 females, with a median age of 41 years (range 7-66). Median follow-up was 54 months (range 8-158). RESULTS: Sixty-three of the 204 patients treated (31%) had treatment failure. Among the 63 patients who relapsed, 60 (95%) experienced local recurrence, and in 49 patients (78%), this was the only site of failure. Two of 63 patients (3%) developed regional lymph node relapse and 3 of 63 (5%) developed surgical pathway recurrence (1 left neck, 1 palate and 1 nasal cavity). Thirteen of 204 patients relapsed in distant sites, accounting for 20% (13 of 63) of all patients with recurrence in this series. The most common metastatic sites were lungs and bones presenting in 7 of 13 and 6 of 13 patients, respectively. Only 2 of 13 patients failed with isolated distant metastasis. The actuarial 3- and 5-year survival rates after local relapse (60 patients) were 44 and 5%, respectively. Following distant failure (13 patients), the 3- and 5-year survival rates were 25 and 12%, respectively. After any relapse (63 patients) the corresponding survival rates were 43 and 7%. Following local relapse, 49 of 60 patients underwent salvage therapy consisting of subtotal resection in most patients (46 of 49). The remaining 11 of 60 patients received supportive care only. Salvage therapy resulted in stable or improved status without subsequent disease progression in 26 of 49 (53%), and progressive disease in 16 of 49 patients (33%). The actuarial 2- and 5-year overall survival rates following relapse for the 49 patients who underwent salvage treatment were 63 and 6%, which favorably compared to the 2-year survival rate of 21% for those who received supportive care only (p = 0.001). CONCLUSION: Local relapse is the predominant type of treatment failure for chordomas of the base of skull and cervical spine. Salvage treatment may relieve symptoms; however, most patients will ultimately succumb to their disease. Poor long-term survival rates following relapse emphasize the importance of a combined treatment approach with experienced surgeons and radiation oncologists at the time of primary treatment. For most patients, only permanent local tumor control will offer a chance of cure.

Adolescent↗

PubMed2006

Management of depression relapse: re-initiation of duloxetine treatment or dose increase.

Continuation of antidepressant therapy after patients have responded to medication has been shown to greatly reduce but not eliminate relapse. We evaluated response to reinstating or increasing drug doses in patients who relapsed during a long-term, randomized, double-blind, continuation phase study of duloxetine treatment for major depressive disorder (MDD). Patients with HAMD17 scores of >18 and CGI-Severity scores of >4 received duloxetine 60 mg QD for 12 weeks, responders then received 26 weeks of duloxetine 60 mg QD or placebo. The relapsing patients who started 12 weeks of rescue treatment received duloxetine 60 mg QD (if relapsing on placebo) or duloxetine 60 mg BID (if relapsing on duloxetine). In the continuation phase, 87 patients received duloxetine 60 mg QD (n=58) or 60 mg BID (n=29) as treatment for relapse. The percentage of patients who responded to treatment after relapse was 62% of those whose dose was increased from 60 mg QD to 60 mg BID, and 74% for those who switched from placebo to duloxetine 60 mg daily. By the end of the study, 32 patients taking duloxetine 60 mg QD were in remission (57%), compared with 11 patients taking duloxetine 60 mg BID (38%). There was significant improvement in HAMD17 and CGI-Severity scores for both groups at endpoint vs. start of treatment for relapse. Significant improvements were seen for all visual analog scale parameters in the 60 mg QD group, but only Interference with Daily Activities and Back Pain parameters showed significant improvement for patients receiving 60 mg BID. Significant within-group improvement from baseline was seen for both groups in Symptom Questionnaire-Somatic Subscale total and pain subscales. Treatment-emergent adverse events were mild/moderate in severity; no clinically significant changes were noted in laboratory results or vital signs. Reinstatement of duloxetine 60 mg QD was effective for patients who relapsed after discontinuing drug. Patients relapsing on duloxetine 60 mg QD benefited from an increase to 60 mg BID. These duloxetine doses were well tolerated and effective, and appear appropriate for MDD patients requiring treatment of relapse.

Adult↗

PubMed1999

The course of depressive symptoms in predicting relapse in schizophrenia: a double-blind, randomized comparison of olanzapine and risperidone.

BACKGROUND: Depressive symptoms are common during the course of schizophrenia and may carry prognostic relevance. METHODS: From a 28-week prospective, double-blind, randomized study of olanzapine and risperidone, a post hoc evaluation of changes on the Positive and Negative Syndrome Scale (PANSS) depression cluster (PDC) and the subsequent risk of relapse were analyzed by logistic regression. RESULTS: Olanzapine was associated with a significantly higher categorical rate of improvement on the PANSS depression cluster (> or = 7 points) (p < .05). Although the baseline severity of depressive symptoms was not a significant predictor of relapse, the degree of acute (8-week) mood improvement on the PANSS depression cluster (but neither negative or positive symptom changes) was related to the probability of a subsequent psychotic relapse. Acute mood improvement with olanzapine was inversely related to a nonsignificantly lower risk of relapse. However, an opposite and significant relationship was observed among risperidone-treated subjects. Risperidone-treated subjects with a greater degree of acute mood change were both 3.58 times more likely to relapse than their risperidone counterparts who had experienced less mood improvement (p = .008) and 8.55 times more likely than olanzapine-treated subjects who had had similar mood improvements (p = .001). CONCLUSIONS: These data suggest the underlying pharmacologic differences between the two drugs may bestow different rates of longer-term mood stabilization and relapse prevention. In a second series of analyses, worsening on the PANSS depression cluster in the 4 weeks or less preceding a clinical relapse was a significant prodromal predictor of relapse among all subjects. As a whole, subjects with a worsening on the PDC demonstrated a 1.77 times higher risk of a relapse during the subsequent 4 weeks (p = .001). Among this mood-worsening stratum, risperidone-treated patients were 3.51 times more likely to relapse in those next 4 weeks (p = .005) than their olanzapine counterparts. Future comparative drug studies in this area will further contribute to our understanding of the pathophysiology of mood change and its relationship to psychosis, including clinical relapse and how newer agents may differ in their respective delivery of long-term treatment outcomes.

Adult↗

PubMed2003

Survival after relapse in patients with endometrial cancer: results from a randomized trial.

OBJECTIVE: The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial. METHODS: The PORTEC trial included 715 patients with stage 1 endometrial cancer, either grade 1 or 2 with deep (>50%) myometrial invasion or grade 2 or 3 with <50% invasion. In all cases an abdominal hysterectomy was performed, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy) or no further treatment. RESULTS: The analysis was done by intention-to-treat. A total of 714 patients were evaluated. At a median follow-up of 73 months, 8-year actuarial locoregional recurrence rates were 4% in the RT group and 15% in the control group (P < 0.0001). The 8-year actuarial overall survival rates were 71 (RT group) and 77% (control group, P = 0.18). Eight-year rates of distant metastases were 10 and 6% (P = 0.20). The majority of the locoregional relapses were located in the vagina, mainly in the vaginal vault. Of the 39 patients with isolated vaginal relapse, 35 (87%) were treated with curative intent, usually with external RT and brachytherapy, and surgery in some. A complete remission (CR) was obtained in 31 of the 35 patients (89%), and 24 patients (77%) were still in CR after further follow-up. Five patients subsequently developed distant metastases, and 2 had a second vaginal recurrence. The 3-year survival after first relapse was 51% for patients in the control group and 19% in the RT group (P = 0.004). The 3-year survival after vaginal relapse was 73%, in contrast to 8 and 14% after pelvic and distant relapse (P < 0.001). At 5 years, the survival after vaginal relapse was 65% in the control group compared to 43% in the RT group. CONCLUSION: Survival after relapse was significantly better in the patient group without previous RT. Treatment for vaginal relapse was effective, with 89% CR and 65% 5-year survival in the control group, while there was no difference in survival between patients with pelvic relapse and those with distant metastases. As pelvic RT was shown to improve locoregional control significantly, but without a survival benefit, its use should be limited to those patients at sufficiently high risk (15% or over) for recurrence in order to maximize local control and relapse-free survival.

Aged↗

PubMed1998

Smoking relapse prevention during pregnancy. A trial of coordinated advice from physicians and individual counseling.

INTRODUCTION: Our objective was to examine the efficacy of physicians' advice and referral to individual counseling in preventing relapse to smoking among women who were smokers early in pregnancy, but quit prior to their first prenatal visit. DESIGN: A randomized controlled trial of prompted physician's advice and individual relapse prevention counseling during pregnancy compared to usual physician advice. Smoking status was assessed by self-report, exhaled carbon monoxide, and urinary cotinine during pregnancy and by self-report 1 year postpartum. RESULTS: There were no significant differences in relapse rates between the intervention and usual-care groups during pregnancy, nor at 1 year postpartum. Relapse rates were 23% in both groups at the 36-week visit, and 32% and 22%, respectively, 1 year postpartum. Younger age, higher motivation to resume smoking, and higher levels of exhaled carbon monoxide at the first prenatal visit were predictive of relapse to smoking during pregnancy. With the conservative assumption that all those lost to follow-up relapsed, the combined 1-year postpartum relapse rate, 51%, was 17 percentage points lower than we observed in an earlier relapse prevention trial, and 15 percentage points lower than that observed nationally a decade earlier. CONCLUSION: Prompting physicians to provide supportive advice combined with referral to individual relapse prevention counseling did not reduce smoking relapse rates during pregnancy, or postpartum. However, the level of attention paid to smoking by physicians in both intervention and usual-care groups during pregnancy may have contributed to the relatively low relapse rates seen 1-year postpartum.

Adult↗

PubMed2003

The effect of retention on orthodontic relapse after the use of small continuous or discontinuous forces. An experimental study in beagle dogs.

Relapse is a major concern in orthodontics for which avoidance retention is the general procedure. However, the effect of retention on relapse after active tooth movement with different force regimes has never been studied in a standardized experimental setting. Mandibular third premolars were extracted in 19 young adult beagle dogs. Three months later, the second premolars were bodily moved distally with forces of 10 cN or 25 cN. The forces were applied for 24 h d-1 or for 16 h d-1. After 4 months, relapse was allowed in half of the animals, while in the others relapse was preceded by retention for 90 d. Statistical analyses were performed on the relation between force regime, active tooth movement, retention, and relapse. Force magnitude had no effect on relapse, while continuous forces resulted in a longer-lasting and more pronounced relapse than did discontinuous forces. A significant positive correlation was found between the amount of active tooth movement and both the rate and the total amount of relapse, but not between the amount of active tooth movement and the duration of the relapse. Retention had no effect on the duration of the relapse, but it strongly decreased its total amount. Finally, the effect of retention on the amount of relapse was strongly correlated with the amount of active tooth movement.

Animals↗

PubMed1997

Risk of extramedullary relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia with leukemia cutis.

Leukemia cutis (LC) is a rare feature of acute myeloblastic leukemia (AML). Little information is available regarding its prognostic influence on post-transplant outcome. In our institution, 202 patients with AML received an allogeneic HLA-identical marrow transplant from related donors between March 1982 and January 1994. Thirteen patients had prior leukemic involvement of the skin (leukemia cutis or LC group) while 189 patients did not (non-LC group). There was a higher incidence of patients with the M4-M5 FAB subtypes in the LC group (83%) as compared to the non-LC group (33%). In addition, the percentage of patients transplanted in relapse was also higher in the LC group (69 vs 15%). While there were no differences observed in the rates of relapse post-transplant in the LC and non-LC groups when matched for stage of disease at transplant, the sites of relapse differed markedly. Five of six relapses in the LC group involved extramedullary sites as compared to only six of 38 relapses in the non-LC group (P = 0.002), with a 6-year probability of extramedullary relapse of 38.5% in the LC group as compared to 3.9% in the non-LC group. This increased probability of extramedullary relapse was independent of the FAB morphology (50 vs 2% for patients with the M4-M5 subtypes in the LC and the non-LC group respectively) and of disease status at the time of transplant. Moreover, only three relapses post-transplant involved the skin, all of which were in the LC group, with a probability of skin relapse of 23.1% in this group. Patients with AML and leukemia cutis have a remarkable propensity to relapse in extramedullary sites following marrow transplantation. These relapses occur in the skin as well as other organs. Further investigations are needed to understand the biological basis of this clinical feature.

Adult↗

PubMed2001

Autotransplants for Hodgkin's disease in first relapse or second remission: a report from the autologous blood and marrow transplant registry (ABMTR).

Although patients with relapsed Hodgkin's disease have a poor prognosis with conventional therapies, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (autotransplantation) may provide long-term progression-free survival. We reviewed data from the Autologous Blood and Marrow Transplant Registry (ABMTR) to determine relapse, disease-free survival, overall survival, and prognostic factors in this group of patients. Detailed records from the ABMTR on 414 patients with Hodgkin's disease in first relapse (n = 295) or second complete remission (CR) (n = 119) receiving an autotransplant from 1989 to 1995 were reviewed. Median age was 29 (range, 7-64) years. Median time from diagnosis to relapse was 18 (range, 6-219) months; median time from relapse to transplant was 5 (range, <1-215) months. Most patients received high-dose chemotherapy without total body irradiation for conditioning (n = 370). The most frequently used high-dose regimen was cyclophosphamide, BCNU, VP-16 (CBV) (n = 240). The graft consisted of bone marrow (n = 246), blood stem cells (n = 112), or both (n = 56). Median follow-up was 46 (range, 5-96) months. One hundred-day mortality (95% confidence interval) was 7 (5-9)%. One hundred and sixty-five of 295 patients (56%) transplanted in relapse achieved CR after autotransplantation. Of these, 61 (37%) recurred. Twenty-four of 119 patients (20%) transplanted in CR recurred. The probability of disease-free survival at 3 years was 46 (40-52)% for transplants in first relapse and 64 (53-72)% for those in second remission (P < 0.001). Overall survival at 3 years was 58 (52-64)% after transplantation in first relapse and 75 (66-83)% after transplantation in second CR (P < 0.001). In multivariate analysis, Karnofsky performance score <90% at transplant, abnormal serum LDH at transplant, and chemotherapy resistance were adverse prognostic factors for outcome. Progression of Hodgkin's disease accounted for 69% of all deaths. Autotransplantation should be considered for patients with Hodgkin's disease in first relapse or second remission. Future investigations should focus on strategies designed to decrease relapse after autotransplantation, particularly in patients at high risk for relapse.

Adolescent↗

PubMed2004

Extramedullary vs medullary relapse after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in multiple myeloma (MM) and its correlation to clinical outcome.

Risk-adapted treatment of multiple myeloma (MM) includes autologous (auto-) and allogeneic (allo-) hematopoietic stem cell transplantation (HSCT). Case reports on extramedullary (EM) compared to bone marrow (BM) relapse after HSCT suggest a dismal prognosis. We compared the outcome of 78 MM patients relapsing after auto- (group A: n = 53) or allo- (group B: n = 25) HSCT, stratified into BM (64 patients) vs EM (14 patients) relapse. The relapse-specific groups were also compared with respect to risk factors, including age, beta2-microglobulin, pretreatment, cytogenetics and stage. EM relapse sites were lungs (5), soft tissue (4), pericardium (2), bone (1), skin (1) and CNS (1). As of May 2004, the overall (OS) and progression-free (PFS) survival after HSCT in patients relapsing from EM sites was not significantly different from BM relapse patients, both after auto- and allo-HSCT. Although MM patients relapsing from EM sites after allo-HSCT used to be regarded as having few therapeutic options, we observed encouraging responses to donor lymphocyte infusions (DLI). Treatment responses to DLIs were observed in 5/9 (56%) BM relapse patients, and in 3/4 (75%) EM relapse patients. These observations suggest that EM relapse after HSCT is common and needs an individualized diagnostic and therapeutic approach in MM during clinical follow-up after HSCT.

Adult↗

PubMed2002

Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy.

The instability of the karyotype may play a role in the development of refractoriness of acute myeloid leukemia (AML) to anti-leukemic therapy. Therefore, in the current study cytogenetic analyses were performed in 117 patients with AML both at diagnosis and at relapse. Changes in karyotype were observed in 38% (36% of initially normal karyotypes, 39% of initially aberrant karyotypes). An evolution of karyotype, ie the acquisition of further aberrations in addition to those present at diagnosis, occurred more frequently in patients with unfavorable karyotypes at diagnosis as compared to all others (60% vs 32%, P = 0.0095). The duration from initial diagnosis to relapse was significantly shorter in cases with an evolution of the aberrant karyotype as compared to cases with no changes in the aberrant karyotype between diagnosis and relapse or with solely regression of aberrations at relapse (9.2 +/- 4.4 vs14.0 +/- 8.5 months, P = 0.0081). In an additional analysis, another cohort of 120 patients with refractory and relapsed AML who were treated uniformly within the respective trial of the German AML Cooperative Group was analyzed cytogenetically at diagnosis and at relapse to further prove the prognostic impact of karyotype aberrations at relapse. Karyotypes were prognostically favorable, intermediate, unfavorable and not available in 8%, 50%, 17% and 25% at diagnosis and in 8%, 49%, 21% and 22% at relapse, respectively. Karyotype aberrations at diagnosis had no impact on response to therapy (P = 0.32) but influenced survival and event-free survival significantly (P = 0.03 and P = 0.02). In contrast, karyotype aberrations at relapse strongly influenced response to therapy (P = 0.05), survival (P = 0.01), and event-free survival (P = 0.002). These data suggest that the instability of the karyotype between diagnosis and relapse and thus karyotype aberrations at relapse in particular contribute to the refractoriness of AML to anti-leukemic therapy.

Acute Disease↗

PubMed2006

Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy.

We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/ 806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26950/mm3 (7700-162000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age <45 years (P=0.05), bcr3 PML-RARalpha isoform (P= 0.0003) and high WBC counts (> or = 10,000/ mm3) (P<0.0001) as risk factors for EM relapse. In multivariate analysis, only high WBC count remained significant (P= 0.001). Patients with EM relapse had a poorer outcome since median survival from EM relapse was 6.7 months as compared to 26.3 months for isolated BM relapse (P=0.04). In conclusion, EM relapse in APL occurs more frequently in patients with increased WBC counts (> or = 10,000/mm3) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC > or = 10,000/mm3 at diagnosis remains to be established.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Have we lost our way? The need for dynamic formulations of smoking relapse proneness.

Current smoking cessation treatments seem to differ from one another in the proportion of ex-smokers who survive the first few days of the quit attempt. After this initial effect, parallel relapse processes appear to unfold in all treatment groups; no available treatments seem to alter the nature of this late relapse process. True relapse prevention will require that we obtain a better understanding of the forces contributing to relapse across the span of the cessation attempt. A working model of dynamic relapse processes may be necessary before treatments can be improved. In this paper, we suggest that the conceptual model of relapse proneness (RP) described originally by the National Working Conference on Smoking Relapse can serve as an ecumenical organizational framework that may be used to integrate and conceptualize relapse data in ways that could generate new strategies for relapse research and inform treatment design. As an illustration, we sketch a preliminary model of RP which postulates that physical withdrawal, stressors/temptations, and cessation fatigue each make independent, time-shifted contributions to relapse risk. A new round of descriptive research focused on relapse proneness processes may be a prerequisite for improving existing smoking cessation interventions.

Administration, Cutaneous↗

PubMed1999

Molecular evolution of acute myeloid leukaemia in relapse: unstable N-ras and FLT3 genes compared with p53 gene.

Relapse is a major cause of treatment failure in acute myeloid leukaemia (AML), and is usually accompanied by resistance to chemotherapy. To study whether relapse is accompanied by genetic alterations, we compared N-ras, p53 and FLT3 gene mutations in paired samples obtained at initial diagnosis and first relapse. 28 patients with relapsed AML were studied, and their duration of complete remission ranged from 133 to 989 d (mean 318 d). Karyotype changes were observed at relapse in 11 patients. Point mutations of the N-ras gene were positive at both stages (+/+) in three patients, positive at initial diagnosis and negative at relapse (+/-) in three patients, and negative at initial diagnosis and positive at relapse (-/+) in two patients. Internal tandem duplications of the FLT3 gene (FLT3/ITD) were +/+ in five patients, +/- in one patient, and -/+ in six patients. The p53 gene mutations were +/+ in two patients, +/- in one patient, and -/- in 25 patients. FLT3/ITD and mutant p53 at relapse were associated with short survival after relapse. These results indicate that relapse is frequently accompanied by molecular alterations that include the loss and/or acquisition of mutations. Thus relapse can be understood as clonal shift or collateral succession rather than clonal progression.

Acute Disease↗

PubMed1999

Evidence to support a change in follow-up policy for patients with breast cancer: time to first relapse and hazard rate analysis.

The ideal follow-up for patients with cancer should be sensitive to the likelihood of relapse, for prompt investigation and treatment if indicated, together with the support of patient confidence. The current British Association of Surgical Oncologists guidelines for patients with breast cancer suggest intensive follow-up, including 3-monthly clinic visits during the first 2 years. These recommendations place increasing demands on clinical resources. The combined outcome of screening, early detection, dedicated clinical services that emphasize rapid diagnosis and concomitant improved survival, have resulted in increasing absolute numbers of diagnosed breast cancer patients in follow-up clinics. This article examines the follow-up of breast cancer patients to determine if the convention should be adjusted to obtain more from current resources while maintaining equivalent patient care. The data on all patients with breast cancer attending one general oncology clinic were examined in order to determine the pattern of relapse. Analyses identified: (1) the time to relapse at any site and at specific sites; and (2) the prognostic significance of three factors for subsequent relapse, namely nodal status, menopausal status and T stage at diagnosis. In 416 consecutive patients, the annual rate of relapse of breast cancer was found to increase progressively over the first 4 years. Nodal disease was the most important single variable as a predictor of relapse. The annual hazard rate for relapse for node positive patients in the first year was 5%; this increased to 10% and 14% in years three and four respectively. In contrast, in those patients who were node negative at diagnosis (302/416; 73%), the hazard rate for relapse was 1% in year one, increasing to 5% in years three and four. Intensive early follow-up of breast cancer patients provides no clear clinical gain for the great majority of patients, since early relapse is rare in the first year. The use of clinical funds and staff resources might be optimized to focus clinical follow-up on those patients at risk of recurrence. We suggest that all patients should continue to be monitored and receive psychological care through access to their general practitioner, skilled breast care nurses and specialized counsellors. Any patient at risk, or developing symptoms of relapse, would have immediate clinical access to the oncologist for diagnostic investigations. This strategy would optimize psychological patient care and use the full backup of clinical resources during the prolonged period over which relapse becomes more probable.

Adult↗