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Relapse factors during maintenance therapy of acute lymphoblastic leukemia in children.

A statistical analysis of possible risk factors for relapse during maintenance therapy (MT) for acute lymphoblastic leukemia (ALL) has been performed. The patient material consists of 64 patients. Twenty-six patients were classified as standard risk (SR), 21 as intermediate risk (IR), and 17 as high-risk (HR) patients. Seventeen patients relapsed and 50 patients (78%) are alive at a median observation period of 86 months (range 39-146 months). Mean white blood cell count (mean WBC) based on weekly determinations, duration of treatment interruption, and the number of infectious episodes were calculated in each patient during the first 6 months of MT. In analyses starting at 6 months after the beginning of MT, these factors were related to relapse risk, time to relapse, and time to infection. Using the median WBC value (3.9 x 10(9)/L) of all patients during the first 6 months as a cutoff point, 14 patients with levels higher, and 3 patients with levels lower relapsed (p = .0004). Adjustment of mean WBC for leukemia risk groups had no influence on the analysis. Time to relapse was related to duration of interruption of MT (p less than .01). Time to relapse was not related to leukemia risk groups. Infection frequency was higher in HR patients compared to SR and IR risk patients (p = .04). As WBC level had a prognostic value and was previously shown to be related to 6-mercaptopurine (6-MP) peak plasma concentration, monitoring 6-MP plasma levels during MT could be helpful for optimizing treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Liver transplantation in patients with hepatocellular carcinoma: factors implicated in tumor relapse.

INTRODUCTION: Liver segmental resection and liver transplantation are both treatments intended for healing liver cancer. An adequate selection of patients eligible for transplantation is crucial, since organs available for transplants are usually scarce. For this reason, awareness of the prognostic factors of relapse is of great importance. We present a comprehensive review of our series in order to better understand these prognostic factors. MATERIAL AND METHODS: We revised the cases of patients with hepatocellular carcinoma who underwent liver transplantation during the period 1994-2000, and present a detailed analysis of a series of variables which may be probably implicated in the appearance of relapse and which have an effect on survival. RESULTS: After a mean follow-up of 33 months, the mortality rate was 27.5% and relapse occurred in 18.75% of cases. No history of alcohol abuse, the number and size of the nodules, the presence of macro and microscopic vascular invasion, and pTNM stage T4 were all factors associated with a significantly increased risk of relapse (p<0.05). These factors and positive HCV were associated to decreased survival. After a multivariate analysis, the size of the nodules and the presence of macroscopic vascular invasion were considered the only independent risk factors for tumor relapse and post-transplantation relapse and mortality, respectively. CONCLUSIONS: Macroscopic vascular invasion and tumor nodules larger than 5 cm are both independent risk factors of tumor relapse after transplantation. Nevertheless, only macroscopic vascular invasion seems to have a significant effect on survival.

Carcinoma, Hepatocellular↗

Risk of relapse among non-lepromatous patients released from treatment after dapsone monotherapy.

Information on 14,625 non-lepromatous patients released from treatment after dapsone monotherapy and followed up to a maximum of 15 years at the ILEP project. Dharmapuri, India, was analysed to study the pattern of relapses. The overall relapse rate was 5/1000 person years. Males had a higher relapse rate than females. The risk of relapse increased with age, number of lesions and duration of treatment. The risk for relapse remained constant over several years after release from treatment. Even though the absolute risk for relapse after MDT may be different, the pattern of relapses and the factors affecting it may be similar to what has been shown in this study.

Adolescent↗

Follow-up of multibacillary leprosy patients using a phenolic glycolipid-I-based ELISA. Do increasing ELISA-values after discontinuation of treatment indicate relapse?

With the introduction of reproducible serological tests it was hoped that relapses in leprosy patients, after discontinuing treatment, could be detected before damaging reactions occurred and before the patients became infectious. The possible value of an ELISA using a semisynthetic analogue of phenolic glycolipid-I to detect antibodies to this antigen in order to predict a relapse in multibacillary patients was investigated. In contrast to that reported for paucibacillary patients, this test was useful to detect early relapses in multibacillary patients. In 3 out of 4 multibacillary patients who relapsed, the ELISA-values were increased. The decreased ELISA-values in the one relapsed patient could be attributed to the corticosteroid therapy. In the multibacillary patients who did not relapse after RFT, the ELISA-values were consistently low or decreased. In only one patient did the ELISA-values increase following his release from treatment and this patient was clinically suspected of developing a relapse.

Adult↗

Erythrocyte sedimentation rate predicts early relapse and survival in early-stage Hodgkin disease. The EORTC Lymphoma Cooperative Group.

OBJECTIVE: To assess the value of an elevated (greater than 30 mm/h) Westergren erythrocyte sedimentation rate (ESR) for predicting early relapse and survival after therapy in patients with clinical stage I or II Hodgkin disease. INTERVENTIONS: We studied 772 patients with early-stage Hodgkin disease who had participated in two separate multicenter clinical trials. Both trials used modern field radiotherapy and, in some patients, multi-agent chemotherapy. MAIN RESULTS: The ESR patterns were based on pretherapy and post-therapy assessments: pattern 1, always normal (n = 261); pattern 2, elevated before therapy but normal immediately after therapy (n = 121); pattern 3, elevated before therapy but normal within 3 months after therapy (n = 89); pattern 4, always elevated (n = 48); pattern 5, normal before therapy but oscillating between normal and elevated after therapy (n = 150); pattern 6, elevated before therapy but oscillating between normal and elevated after therapy (n = 130). By multivariate analysis, independent of whether or not patients received chemotherapy in the initial therapy protocol, ESR patterns 4, 5, and 6 were shown to be the best predictors for early relapse and survival when patients were stratified according to the type of chemotherapy received and the number of involved nodal areas. Patients with ESR pattern 4 had a relative risk for death seven times that of patients with patterns 1, 2, or 3. Early relapse was the second most important factor predicting death, irrespective of ESR; patients with early relapse and ESR patterns 1, 2, or 3 had a relative risk for death of 4.5, and those with early relapse and ESR patterns 4, 5, or 6 had a relative risk for death of 15. Whether or not chemotherapy was given initially did not change the relative risk, which shows that ESR, not initial therapy, was the predictor for early relapse and death due to Hodgkin disease. CONCLUSION: An unexplained elevated ESR after therapy, especially after modern radiotherapy, independent of other factors, strongly suggest the presence of aggressive and resistant Hodgkin disease. An elevated ESR is predictive of early relapse and poor prognosis; its presence justifies early aggressive therapy.

Adult↗

Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis.

OBJECTIVE: To examine possible risk factors for relapse, including chronic nasal carriage of Staphylococcus aureus and serial antineutrophil cytoplasmic antibody (ANCA) determinations in patients with Wegener granulomatosis. DESIGN: Observational cohort study. SETTING: Outpatient clinic at a university-affiliated hospital. PATIENTS: Consecutive patients (n = 71) with biopsy-proven Wegener granulomatosis who were seen during follow-up at the outpatient clinic from January 1988 to July 1991. Fourteen patients were ineligible or dropped out; 57 patients were analyzed. MEASUREMENTS: Serial ANCA determinations and swab cultures of both anterior nares for S. aureus taken at each visit every 4 to 6 weeks. Occurrence of infections and relapses of Wegener granulomatosis were identified according to strict, predefined criteria. RESULTS: Thirty-six of the 57 patients (63%; 95% CI, 49% to 76%) were found to be chronic nasal carriers of S. aureus (> or = 75% of nasal cultures positive for S. aureus). Proportional-hazards regression analysis identified chronic nasal carriage of S. aureus (adjusted relative risk, 7.16; CI, 1.63 to 31.50), creatinine clearance above 60 mL.min-1 (adjusted relative risk, 2.94; CI, 1.27 to 6.67), and a history of previous relapses of Wegener granulomatosis (adjusted relative risk, 1.33; CI, 0.98 to 1.78) as independent risk factors for relapse. Twenty-two of 33 patients persistently or intermittently positive for ANCA had a relapse as opposed to only 1 of 21 persistently negative patients. Relapses of Wegener granulomatosis were not related to diagnosed infections. CONCLUSION: Chronic nasal carriage of S. aureus identifies a subgroup of patients with Wegener granulomatosis who are more prone to relapses of the disease, suggesting a role for S. aureus in its pathophysiology and a possible clue for treatment.

Adult↗

Preoperative p53, bcl-2, CD44 and E-cadherin immunohistochemistry as predictors of biochemical relapse after radical prostatectomy.

PURPOSE: Since radical prostatectomy is performed to cure prostate cancer, identification of markers enabling preoperative prediction of relapse after radical prostatectomy is essential to counsel and select patients for adjuvant therapy. Aberrant p53, bcl-2, CD44 and E-cadherin immunohistochemistry has been associated with aggressiveness in prostate cancer. We assessed these biomarkers in biopsy and radical prostatectomy specimens as predictors of biochemical relapse. MATERIALS AND METHODS: A total of 76 patients with untreated clinically localized prostatic adenocarcinoma underwent radical prostatectomy. Preoperative (prostate specific antigen, biopsy Gleason score) and postoperative (pathological stage and margin status) variables, biopsy and radical prostatectomy biomarker immunohistochemistry were correlated with relapse. Univariate and multivariate statistical analyses identified significant predictors. RESULTS: Of the 76 patients 23 (30%) had relapse (mean followup 38 months). Aberrant p53, bcl-2, CD44 and E-cadherin expression was observed in 64, 12, 85 and 12% of biopsies and 57, 20, 64 and 49% of radical prostatectomy specimens, respectively. Biopsy Gleason 7 to 10 and biopsy p53, respectively, gave the highest positive and negative predictive values for relapse. Relapse occurred in 13% of patients with normal biopsy p53 and in half with aberrant p53. Multivariate analysis revealed Gleason score and p53 to be independent preoperative predictors (p = 0.01 and 0.02, respectively). Estimated risk of relapse was 3.5 times higher in patients with Gleason scores 7 to 10 and 24% higher in those with aberrant p53. Significant postoperative predictors were bcl-2, p53, Gleason score and margin status (p = 0.01, 0.01, 0.04 and 0.01, respectively). CONCLUSIONS: Aberrant biopsy p53 is associated with a significantly worse outcome after radical prostatectomy than normal p53, highlighting a potential clinical role for p53. Postoperative p53 and bcl-2 were significant predictors of outcome after radical prostatectomy.

Aged↗

Acquisition of p16(INK4A) and p15(INK4B) gene abnormalities between initial diagnosis and relapse in children with acute lymphoblastic leukemia.

Although numerous somatic mutations that contribute to the pathogenesis of childhood acute lymphoblastic leukemia (ALL) have been identified, no specific cytogenetic or molecular abnormalities are known to be consistently associated with relapse. The p16(INK4A) (p16), which encodes for both p16(INK4A) and p19(ARF) proteins, and p15(INK4B) (p15) genes are inactivated by homozygous deletion and/or p15 promoter hypermethylation in a significant proportion of cases of childhood ALL at the time of initial diagnosis. To determine whether alterations in these genes play a role in disease progression, we analyzed a panel of 18 matched specimen pairs collected from children with ALL at the time of initial diagnosis and first bone marrow relapse for homozygous p16 and/or p15 deletions or p15 promoter hypermethylation. Four sample pairs contained homozygous p16 and p15 deletions at both diagnosis and relapse. Among the 14 pairs that were p16/p15 germline at diagnosis, three ALLs developed homozygous deletions of both p16 and p15, and two developed homozygous p16 deletions and retained p15 germline status at relapse. In two patients, p15 promoter hypermethylation developed in the interval between initial diagnosis and relapse. In total, homozygous p16 deletions were present in nine of 18 cases, homozygous p15 deletions in seven of 18 cases, and p15 promoter hypermethylation in two of eight cases at relapse. These findings indicate that loss of function of proteins encoded by p16 and/or p15 plays an important role in the biology of relapsed childhood ALL, and is associated with disease progression in a subset of cases.

Carrier Proteins↗

Role of endogenous interleukin-12 (IL-12) in induced and spontaneous relapses of experimental autoimmune encephalomyelitis in mice.

Actively induced, chronic relapsing experimental autoimmune encephalomyelitis (CREAE) was studied in SJL/J and in Biozzi ABH mice. In Biozzi ABH mice, relapses occurred spontaneously with high frequency. In SJL/J mice, spontaneous relapses occurred infrequently; however they could be induced reproducibly by reimmunization. In both models, moderately increased levels of serum IL-12(p40) were consistently found shortly before primary attacks, but irregularly at later times. Injections of anti-IL-12 antibody inhibited disease development in both SJL/J and in Biozzi ABH mice. The time window during which treatment needed to be initiated in order to be effective, ranged from before induction until shortly before the symptoms of primary attacks emerged. Such treatment inhibited not only the first attack but also the spontaneous or induced relapses. Most significantly, anti-IL-12 antibody given during remission of primary disease inhibited actively re-induced relapses in SJL/J, but not spontaneous relapses in Biozzi ABH mice. These results indicate that endogenous IL-12 favours EAE development by crucially affecting the active induction process, but that a second burst of IL-12 production may not be necessary for triggering spontaneous relapses.

Animals↗

Minimal residual disease in patients with hairy cell leukemia in complete remission treated with 2-chlorodeoxyadenosine or 2-deoxycoformycin and prediction of early relapse.

The purine nucleoside analogues 2-chlorodeoxyadenosine (2-CdA) and 2'-deoxycoformycin (2'-DCF) induce complete remission (CR) in the majority of patients with hairy cell leukemia. However, minimal residual disease (MRD) has been detected in bone marrow core biopsies using immunohistochemical techniques in patients achieving CR by conventional criteria. This study was designed to compare the prevalence of MRD with each agent in patients in CR by using conventional criteria and the relapse-free survival for patients with and without MRD. Bone marrow biopsies from 39 patients treated with a single cycle of 2-CdA and 27 patients treated with multiple cycles of 2'-DCF were studied. The monoclonal antibodies anti-CD20, DBA.44, and anti-CD45RO were used to evaluate the paraffin-embedded bone marrow core biopsies for MRD. Five of 39 patients (13%) treated with 2-CdA had MRD, as compared to 7 of 27 patients (26%) treated with 2'-DCF (two-tailed P = 0.21). Relapse has occurred in two of the five patients with MRD after 2-CdA treatment and in four of the seven patients with MRD after 2'-DCF treatment. In total, 6 of the 12 patients (50%) with MRD have relapsed, whereas 3 of 54 patients (6%) without MRD have relapsed, and 2 patients have died without evidence of relapse. The estimated 4-year relapse-free survival among patients with MRD is 55% (+/- 15%, SE), compared to 88% (+/- 5%, SE) among patients without MRD (two-tailed P = 0.0023). The prevalence of MRD detected in a subset of patients in CR after either 2-CdA or 2'-DCF treatment did not differ significantly. However, the presence of MRD is associated with an increased risk of relapse.

Adult↗

Polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study.

Glutathione S-transferases (GSTs) have been associated with outcome in human cancers treated with cytotoxic chemotherapy. In a case-control study, we investigated the association between polymorphisms within the GSTM1, GSTT1, and GSTP1 genes and risk of relapse in childhood acute lymphoblastic leukemia (ALL). Cases were relapsed patients. Controls were successfully treated patients with a minimum follow-up of 5 years. The null genotype (absence of both alleles) for GSTM1 or GSTT1 conferred a 2-fold (OR = 0.5, 95% CI = 0. 23-1.07, P =.078) and 2.8-fold (OR = 0.36, 95% CI = 0.13-0.99, P =. 048) reduction in risk of relapse, respectively, relative to the presence of the GSTM1 or GSTT1 gene. The GSTP1 Val(105)/Val(105) genotype showed a 3-fold decrease in risk of relapse (OR = 0.33, 95% CI = 0.09-1.23, P =.099) in comparison to the combined category of Ile(105)/Val(105) and Ile(105)/Ile(105 )genotypes. No particular associations with relapse were observed for the GSTP1 polymorphism at codon 114. The risk of relapse when having 1 of the low-risk genotypes (GSTM1 null, GSTT1 null, GSTP1 Val(105)/Val(105)) decreased 1.9-fold (OR = 0.53, 95% CI = 0.24-1.19, P =.123), and the risk when having 2 or 3 low-risk genotypes 3.5-fold (OR = 0.29, 95% CI = 0.06-1.37, P =.118), compared with individuals having no low-risk genotype (P for trend =.005). Our results suggest that polymorphisms within genes of the GST superfamily may be associated with risk of relapse in childhood ALL. (Blood. 2000;95:1222-1228)

Adolescent↗

Elevations in serum soluble interleukin-2 receptor levels predict relapse in patients with hairy cell leukemia.

PURPOSE: Interferon-alfa, 2'-deoxycoformycin, and 2-chlorodeoxy-adenosine (2-CdA) are effective in the management of patients with hairy cell leukemia. These agents produce remissions in most patients, but relapses occur with all three drugs. The optimal means to follow patients for relapse after treatment has not been determined. METHODS: We retrospectively examined serial serum soluble interleukin-2 receptor levels (sIL-2R) and absolute granulocyte counts in eight patients with relapsed hairy cell leukemia. All were treated with 2-CdA at the time of relapse. Serum samples were available at 3- to 6-month intervals from 5 to 9 years before relapse and 2-CdA treatment RESULTS: sIL-2R levels increase only in patients who go on to relapse. sIL-2R levels doubled a mean of 17.1 months (range, 4-36 months) before absolute granulocyte count decreased by 50%. DISCUSSION: Demonstration of a rising serum sIL-2R level in patients with hairy cell leukemia identified those with an increased risk of relapse who need more frequent observation than patients who maintain a stable sIL-2R level. Early intervention may ameliorate the toxicity of salvage therapy because disease-related neutropenia may be anticipated.

Antineoplastic Agents↗

The effect of cystectomy, and perioperative methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy on the risk and pattern of relapse in patients with muscle invasive bladder cancer.

PURPOSE: Trials have demonstrated decreased relapse with perioperative methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy in patients with muscle invasive bladder cancer. We evaluated whether the benefit of chemotherapy correlates with its effects on distant or pelvic relapse. MATERIALS AND METHODS: We retrospectively evaluated the records of all 107 patients who underwent cystectomy for muscle invasive bladder cancer at our institution between 1988 and 1994. Factors predicting relapse were identified and used to group patients at high or low risk. The outcome in each group with and without M-VAC chemotherapy was then analyzed in terms of overall, metastatic and pelvic relapse. Univariate analysis was performed using the Kaplan-Meier method and log rank statistic, and multivariate analysis was done using the Cox proportional hazards model. Median survival was 29 months for patients free of disease. RESULTS: Pathological stage T3 or greater according to the American Joint Committee on Cancer, tumor greater than 3 cm. and creatinine greater than 1.5-fold normal were independent poor prognostic factors in patients treated with cystectomy only. Patients with any of these factors or metastatic involvement of the pelvic lymph nodes were considered at high risk. All 35 low risk patients were treated with cystectomy only and had an excellent outcome with a 3-year relapse-free survival plus or minus standard error of 93% +/- 5%. The 3-year rates in 52 and 20 high risk patients treated without and with chemotherapy, respectively, were 42% +/- 8% versus 57% +/- 13% for relapse-free survival (p = 0.17), 38% +/- 9% versus 8% +/- 8% for pelvic failure (p = 0.02) and 39% +/- 9% versus 38% +/- 13% for distant metastases (not significant). Multivariate analysis of patients who underwent pelvic lymphadenectomy revealed that perioperative chemotherapy improved relapse-free survival and pelvic control but not metastatic control (p = 0.03, 0.02 and 0.31, respectively). CONCLUSIONS: Low risk patients have excellent disease control when treated with cystectomy only. Those with high risk features are at substantial risk for pelvic failure (38% at 3 years) after cystectomy only. Perioperative M-VAC chemotherapy has a profound impact on pelvic but not on metastatic failure.

Aged↗

Risk assessment in patients with Ph+ chronic myelogenous leukemia at first relapse after allogeneic stem cell transplant: an EBMT retrospective analysis. The Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Patients with Ph+ chronic myelogenous leukemia who relapse after a first allogeneic stem cell transplant still have a possibility of long-term survival. To assess the value of the individual therapeutic options, the factors predicting outcome should be identified. We investigated data from 500 patients who relapsed before July 1996; follow-up was updated during 1998. The actuarial survival from relapse was 34.2% (95% confidence interval [CI]: 29. 9%-38.5%) at 5 years and 23.4% (95% CI: 18.9%-27.9%) at 10 years. Survival after relapse was significantly related to 5 factors: time from diagnosis to transplant (< 2 years vs >/= 2 years), disease phase at transplant (first chronic phase vs other), disease stage at relapse (cytogenetic or chronic phase vs advanced phase), time from transplant to relapse (< 1 year vs >/= 1 year), and donor type (HLA-identical sibling vs volunteer unrelated donor). The effects of individual adverse risk factors were cumulative: The probability of survival at 10 years decreased stepwise from 42% (0 factors), 32% (1 factor), 14% (2 factors), 3% (3 factors), to 0% (4 or 5 factors). Novel strategies for high-risk patients are warranted. We conclude that these 5 factors should be taken into account when comparing results of salvage therapies in patients with Ph+ chronic myeloid leukemia relapsing after allogeneic stem cell transplant.

Actuarial Analysis↗

Nephrotic syndrome in children: a randomized trial comparing two prednisone regimens in steroid-responsive patients who relapse early. Report of the international study of kidney disease in children.

Fifty-four children with steroid-responsive nephrotic syndrome relapsing within 6 months of their initial response were randomly allocated to receive two different regimens of prednisone therapy. The test regimen differed from the standard prednisone relapse regimen used by the International Study of Kidney Disease in Children in that the total dosage was about double, and the duration of daily therapy (8 weeks vs. a mean of 12 days) as well as the total duration of treatment (8 weeks vs. a mean of approximately 6 weeks) was longer. The proportion of patients relapsing during treatment was significantly smaller (8% vs. 40%) and the length of remission following treatment was significantly longer (3.27 vs. 1.48 months) in the test group. All patients in both groups relapsed by 8 months. During a period of approximately 6 months after this relapse, neither the frequency of relapses nor the mean number of days of proteinuria differed significantly. Opinions of participants in this multicenter trial varied concerning whether these statistically significant differences clinically justified exposing patients to the more intensive treatment regimen. However, all agreed that neither form of treatment was satisfactory in terms of preventing subsequent relapses.

Adolescent↗

American cutaneous leishmaniasis: use of a skin test as a predictor of relapse after treatment.

While relapses following clinical cure of American cutaneous leishmaniasis are frequent, no test has been described until now to predict such relapses. A cohort of 318 American cutaneous leishmaniasis patients was followed up for two years after treatment with meglumine antimoniate, during which time 32 relapses occurred, 30 in the first year and two in the second (accumulated risk: 10.5%). No association was found between these relapses and the parasite-specific antibody response before and after treatment, or between the relapses and stratification by sociodemographic and clinical characteristics. However when Leishmania was used as antigen, patients with a negative skin test at the time of diagnosis presented a 3.4-fold higher risk (hazard risk = 3.4; 95% confidence interval, 1.7-7.0) of American cutaneous leishmaniasis relapse, compared with patients with a positive response. This result shows that the skin test can be a predictor of American cutaneous leishmaniasis relapse after treatment.

Adolescent↗

[High-dose chemotherapy and autologous stem cell transplantation for refractory and relapsing Hodgkin's disease as first-line therapy-- studies at Sheba Medical Center--Tel Hashomer].

High dose chemotherapy and autologous stem cell transplantation are widely used in relapsed and primary refractory Hodgkin's disease. We transplanted 42 patients with Hodgkin's disease between 1990-1998. Median follow-up was 31 months (range 1-102). 29 (69%) were transplanted after relapse and 13 (31%) were refractory to first line therapy. Median age at transplantation was 29 years (range 19-58) and 23 (55%) were males. All were treated with the BEAM protocol (carmustine, etoposide, cytarabine and melphelan). 18 who were in remission received radiotherapy following transplantation. The source of the stem cells was bone marrow in 17% and peripheral blood in 83%. At initial diagnosis: 57% had stage III-IV disease and B symptoms were present in 52%. 75% were treated with MOPP, ABVD or with related versions. Radiotherapy followed in 52%. Prior to transplantation, 45% of the relapsed group were in the advanced stage. 33% and 12% of all patients had lung and bone involvement, respectively. The complete remission rate was 86% for the 2 groups. 2 (5%) died from transplant-related complications and MDS/AML developed in 2 (5%) after transplantation. The 3-year overall survival (OS) and disease-free survival (DFS) were 68% and 60%, respectively. The 3-year OS for the relapsed group was 64% compared with 76% for the refractory group, and the 3-year DFS for the relapsed group was 60% vs. 42% for the refractory group (neither difference significant). Radiotherapy following transplantation did not have a beneficial effect on DFS. No prognostic factors for outcome of transplantation were found, most probably due to the limited number of patients and the high variability of disease characteristics. We conclude that high dose chemotherapy and autologous stem cell transplantation are effective and relatively safe for relapsed or primary refractory Hodgkin's disease. The DFS at 3 years was longer for those transplanted after relapse than those with primary refractory disease, but not significantly. Patients with primary refractory disease can be salvaged with high dose chemotherapy.

Adult↗

Aggressive salvage treatment is not appropriate for the majority of elderly patients with acute myeloid leukemia relapsed from first complete remission.

BACKGROUND AND OBJECTIVES: The prognosis of acute myeloid leukemia (AML) in the elderly is still poor because of different reasons, including a high incidence of relapse. The aim of this study was to investigate whether aggressive salvage chemotherapy (CHT) results in an actual survival advantage in elderly patients with relapsed AML, as well as to compare hospitalization and load of supportive treatment between patients receiving aggressive management or only palliation. DESIGN AND METHODS: One hundred and fifty consecutive patients with relapsed AML (median age 66 years) were analyzed. At relapse, 99 (66%) were treated with CHT, and 51 had palliative management. RESULTS: Second complete remission (CR2) was achieved in 36/99 patients (36%) receiving CHT, while no CR was observed in the other group (p<0.001). Induction death rate was 22%, while 41% were resistant to CHT. The median survival from relapse was 4 months for the whole patient population; according to management, it was 5 months and 3 months for CHT and palliation, respectively (p=0.01). As to patients given CHT, a CR1 duration of more than 12 months was the only parameter significantly related to a better clinical outcome (survival from relapse: 8 vs. 4 months, p=0.002; CR2 duration: 11 vs. 5 months, p=0.001, respectively). Finally, patients managed with palliation required less hospitalization and less supportive therapy as compared to the CHT group. INTERPRETATION AND CONCLUSIONS: Aggressive chemotherapy results in an actual survival advantage only for a minority of elderly patients with relapsed AML, i.e. those with CR1 lasting for more than 12 months.

Acute Disease↗