Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a population-based study. Nordic Myeloma Study Group

High-dose therapy has become a common treatment for myeloma. The objectives of this study were to estimate in a prospective, population-based setting the impact on survival of high-dose therapy in newly diagnosed, symptomatic patients less than 60 years old and to compare the results with those of conventionally treated historic controls. The prospective population comprised 348 patients. Of these, 274 were treated according to a specified intensive-therapy protocol (Nordic Myeloma Study Group [NMSG] #5/94) and constituted the intensive-therapy group. The historic population consisted of 313 patients identified from 5 previous population-based Nordic studies. Of these, 274 fulfilled the eligibility criteria for high-dose therapy stated in NMSG #5/94 and constituted the control group. The expected numbers of patients in the prospective population and the historic population were 450 and 410, respectively, estimated from previously established data on the incidence in this population and the population base for each study. Survival was prolonged in the intensive-therapy group compared with the control group (risk ratio for the control group 1.62; 95% confidence interval 1.22-2.15; P =.001). These groups represented more than 60% of the expected number of patients. When survival for all the registered patients in the 2 populations was compared, representing more than 75% of the expected number of patients, the advantage for the prospective population persisted (risk ratio for the historic population 1.46; 95% confidence interval 1.14-1.86; P =. 002). These results indicate that the introduction of high-dose therapy for newly diagnosed myeloma has resulted in prolonged survival for the total patient population aged less than 60 years. (Blood. 2000; 95:7-11)     

Intensification thérapeutique et autogreffe de cellules souches hématopoïétiques (CSH) dans le traitement des cancers du sein métastatiques : résultats du programme national Pegase 04

We report hereby the results of the french multicentric randomized PEGASE 04 protocol established to evaluate the impact on survival of high-dose chemotherapy over conventional chemotherapy for MBC patients.Patients and methods:Inclusion criteria were : age < 60 year, PS < 2, adenocarcinoma initially metastatic or in first relapse, chemosensitive disease. Randomization was done after 4-6 courses of conventionnal chemotherapy between high-dose (Mitoxantrone, 45 mg/m², Cyclophosphamide 120 mg/kg, Melphalan 140 mg/m²), and the pursuit of the same conventionnal chemotherapy. Between 09/92 and 12/96, 61 chemosensitive patients were enrolled 29 were referred to standard chemotherapy, 32 to intensive therapy. At randomization, 13 pts (21.3%) were in complete response and 48 in partial response.ResultsThe median progression-free survivals were 20 and 35.3 months in the standard and intensive groups (p=0.06). The relapse rates were respectively 79.3% vs 50.8% at 3 years and 90.8% vs 90.7% at 5 years. The median overall survivals were 20 and 43.4 months, with an overall survival rate of 18.5% vs 29.8% at 5 years (p=0.12).Conclusion The CMA regimen could prolong the progression-free survival of MBC patients, however without any significant impact on overall survival.Remerciements: Ligue Nationale Contre le Cancer, les laboratoires Amgen, Pharmacia-Upjohn et Lederle     

The impact of age, Charlson comorbidity index, and performance status on treatment of elderly patients with diffuse large B cell lymphoma

Treatment intensity will affect outcome in elderly patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 333 DLBCL patients aged over 60 years who were diagnosed between January 2003 and December 2010 to evaluate the difference between different treatment regimens. The median age was 73 years; 56.8 % of patients received treatment with rituximab-containing regimens. In univariate analysis, patients with younger age, better performance status, early Ann Arbor stage, lower International Prognostic Index (IPI), normal serum lactate dehydrogenase, normal serum albumin, or normal serum beta-2 microglobulin received more intensive treatment regimens. In multivariate analysis, patients with younger age (p < 0.001) or better performance status (p = 0.027) received treatment of more intensive regimens. The treatment regimens were not different between patients with lower and higher Charlson comorbidity index (CCI). Female gender, normal serum beta-2 microglobulin, lower CCI, lower IPI, and treatment with more intensive regimens predicted better progression-free survival and overall survival in multivariate analysis. Patients treated with rituximab-containing regimens had better progression-free survival (median 22.2 vs. 9.9 months, p = 0.005) and better overall survival (median 34.9 vs. 21.8 months, p = 0.042) as compared to those treated without rituximab. In conclusion, our results showed that patients with younger age or better performance status received more intensive treatment. The treatment regimen was not different between patients with lower and higher CCI. Rituximab-containing regimens improved the outcome of elderly patients with DLBCL.     

Heart failure in beta thalassemia: a 5-year follow-up study

PURPOSE: To evaluate the survival of patients with beta thalassemia and heart failure who were treated with iron chelation therapy. SUBJECTS AND METHODS: Fifty-two consecutive patients with beta thalassemia and heart failure were followed in a prospective 5-year study. All patients underwent a full clinical examination with chest radiograph, electrocardiogram, and echocardiographic investigation performed at 6-month intervals or when a new symptom developed. RESULTS: Of the 52 patients (mean [+/- SD] age, 24 +/- 5 years), 25 (48%) survived 5 years after the onset of heart failure. Forty-three patients had left-sided heart failure, and 9 had right-sided heart failure. Those with left-sided heart failure were younger at presentation with heart failure (22 +/- 4 years vs. 31 +/- 6 years; P <0.001), had lower ejection fractions (36% +/- 9% vs. 64% +/- 10%; P <0.001), and had a lower mean serum ferritin level (3355 +/- 1241 ng/mL vs. 6,397 +/- 1,613 ng/mL; P <0.001). CONCLUSION: The 5-year survival rate in patients with beta thalassemia with heart failure was greater than previously reported. There are clinical characteristics that may make patients more likely to develop left- or right-sided heart failure.     

Clinical Characteristics and Outcomes in Patients with Advanced Rectal Cancer: A National Prospective Cohort Study

Purpose At the time of diagnosis, approximately one third of patients with rectal cancer present with advanced disease. In this study we focus on a group of patients with primary advanced rectal cancer considered as not operable. We address various clinical aspects relevant for decision-making in a group of patients in need of palliative care. Methods Between January 1997 and December 2001, 4831 consecutive patients with rectal cancer were prospectively registered in the Norwegian Rectal Cancer Registry. In this national population-based cohort, 386 patients (8 percent) without surgical interventions were identified. These patients comprise the study population. Clinical characteristics and survivals were addressed. Results Patients not surgically treated were significantly older compared with other treatment groups (median age, 80 years; interquartile range, 72–86 vs. median age, 71 years; interquartile range, 62–79 years) (P<0.001). Median survival time was 4.5 (range, 3.5–5.4) months, regardless of age, gender, or hospital category. Patients who received radiotherapy had a significantly increased survival (P<0.001) compared with patients not treated with radiation, with a median survival time of 10.2 (range, 7.3–12.1) months vs. 2.8 (range, 2.1–3.6) months, respectively. Use of chemotherapy was not associated with improved survival. In multivariate analysis, only stage of disease and radiotherapy were independent predictors of better survival. Conclusion Higher age and comorbidity seem to influence choice of treatment in this subgroup of patients with advanced rectal cancer disease. In nonsurgically treated patients, radiotherapy was associated with an improved survival. Our prospective, population-based cohort study emphasizes the dismal prognosis of these patients, which also should challenge our efforts and clinical approaches in palliative care. Dr. H. K. Sigurdsson, M.D., is a Reseach Fellow sponsored by the Western Norwegian Regional Health Authorities (Project No. 911158). Reprints are not available.     

Acute nonlymphocytic leukemia in the elderly: results of a retrospective study

Seventy-four patients over 60 years of age with new cases of ANLL diagnosed between January, 1980 and December, 1986 were retrospectively evaluated. Twenty-nine (median age 63, range 60-70) received aggressive induction polychemotherapy: 15 achieved CR (52%), 10 were resistant (34.5%) and 4 died during induction (13.5%). Overall median survival was 6 1/2 months, median CR duration and median survival of responders were 9 and 13 months, respectively. Eight patients (median age 70.4, range 64-74) received low doses of Ara-C: 2 achieved CR, 5 were resistant and 1 died during induction, with an overall median survival of 6 1/2 months; 37 patients (median age 72, range 60-86) received only supportive care and cytostatic therapy for disease control with Hydroxyurea and 6-Mercaptopurine if WBC greater than 20 x 10(9)/l: overall median survival was 6 months and 2 patients are still alive after 18 and 26 months. Aggressive chemotherapy seems to be the treatment of choice in patients less than or equal to 70 years, while for those over 70 current supportive care may offer good survival and a good quality of life.     

Age does not impair the efficacy of immunochemotherapy in patients with metastatic renal carcinoma

PURPOSE: Based on the increasing proportion of elderly cancer patients, we compared the efficacy of subcutaneous cytokine based home therapy in older (age > or = 60 years) and younger (age < 60 years) patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: As a rule, patients at an age of 60 years or older received a 20% dose reduction of s.c. IL-2. Treatment consisted of (A) s.c. interferon-alpha2a (s.c. INF-alpha2a), s.c. interleukin-2 (s.c. IL-2), (B) s.c. IFN-alpha2a, s.c. IL-2 and i.v. 5-fluorouracil (5-FU) or (C) s.c. IFN-alpha2a, s.c. IL-2 and i.v. 5-FU combined with p.o. 13-cis-retinoic acid (p.o. 13cRA). RESULTS: Patient age groups > or = 60 years (n=174) and < 60 years (n=251) showed no significant difference in objective response (27% versus 31%), in median overall survival (22 months versus 19 months), and in progression-free survival (6 months versus 5 months). Within the elderly patients group, median overall survival was 20 months (pts. 60-64 years) versus 23 months (pts. > or = 65 years) and median progression-free survival was 4 months (pts. 60-64 years) versus 8 months (pts. > or = 65 years). CONCLUSION: Our results demonstrated that patient age and related IL-2 dose reduction do not impair the efficacy of s.c.-IL-2 plus s.c.-INF-2a based outpatient immunochemotherapy in metastatic renal carcinoma.     

Lack of influence of human immunodeficiency virus infection status in the response to therapy and survival of adult patients with mature B-cell lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study

BACKGROUND AND OBJECTIVES: Short, intensive multiagent chemotherapy has resulted in significant progress in Burkitt's lymphoma and leukemia. A protocol was designed to treat all adult patients with mature B-cell lymphoma or leukemia with the aims of comparing the response to therapy and survival with regards to their HIV infection status. DESIGN AND METHODS: Fifty-three adult patients with advanced stage Burkitt's lymphoma or Burkitt's leukemia were treated. Response to therapy, survival and toxicity were evaluated according to their HIV infection status. RESULTS. The median age of the patients was 53 years (range 15-74). There were no differences in CR rates between HIV-negative (77%) and HIV-positive patients (71%). Only age > 60 years was associated with a lower CR rate (OR 0.18, 95%CI 0.04-0.81, p=0.026). The 2-year overall survival (OS) probability was 51% (95%CI, 38%-64%) for the 53 patients. The OS of HIV-negative and HIV-positive patients did not significantly differ. Only age > 60 years was associated with a shorter OS (OR 5.1, 95%CI 2.0-12.7, p=0.001). The 2-year disease free survival (DFS) for the 40 patients achieving CR was 60% (95%CI, 45%-75%). Age > 60 years was the only identified factor associated with a shorter DFS (OR 5.2, 95%CI 1.4-20, p=0.015). INTERPRETATION AND CONCLUSIONS: This study confirms the effectiveness of intensive strategies in adult patients with advanced stage Burkitt's lymphoma or leukemia. It also shows the feasibility of these strategies in individuals with HIV infection with comparable results. Advanced age proved to be the main adverse prognostic factor for response to therapy and survival.     

Lung cancer in patients < 50 years of age: the experience of an academic multidisciplinary program.

OBJECTIVE: To determine if the clinicopathologic features and survival of lung cancer patients < 50 years of age differ from those of older patients. DESIGN: Retrospective review of patients with primary bronchogenic carcinoma diagnosed at a single, multidisciplinary cancer center. SETTING: A National Cancer Institute-designated comprehensive cancer center in urban Detroit, MI. PATIENTS: All patients with primary bronchogenic carcinoma evaluated in the Multidisciplinary Lung Cancer Clinic at the Barbara Ann Karmanos Cancer Institute between 1990 and 1993. RESULTS: Of 1,012 patients with lung cancer, 126 (12.5%) were < 50 years old at diagnosis, with a median age of 44 years. The median age of the 886 patients > or = 50 years of age was 65 years. The gender (p = 0.08) and racial (p = 0.12) characteristics of the younger and older patient groups were not significantly different. More than 90% of patients in both groups were smokers. The incidence of adenocarcinoma was significantly higher in younger patients (48.4% vs 36.0%, p < 0.001), and early-stage disease was less frequently diagnosed in younger patients (4.8% vs 19.7%, p < 0.001). Younger patients were more likely than older patients to undergo treatment, including surgery and combined-modality therapy (p < 0.001). Median survival was 13 months in younger and 9 months in older patients, while overall survival was similar in younger and older patients (p = 0.13). CONCLUSIONS: Although younger patients with lung cancer present with more advanced-stage disease, their overall survival is similar to that of older patients, suggesting that lung cancer is not an inherently more aggressive disease in patients < 50 years of age.     

Peripheral T-cell non-Hodgkin's lymphomas of low malignancy: prospective study of 25 patients with pleomorphic small cell lymphoma,lymphoepitheloid cell (Lennert's) lymphoma and T-zone lymphoma

Peripheral T-cell lymphomas comprise a heterogenous group of low- and high-grade malignancies differing in their histopathological appearance and also in clinical and prognostic aspects. We prospectively studied 25 patients with low-grade peripheral T-cell lymphomas: pleomorphic, small cell lymphoma (PSC) (n = 9), lymphoepitheloid (Lennert's) lymphoma (LEL) (n= 12) and T-zone lymphoma (TZL) (n= 4). The median patient age was 55 years (range 19-75 years); the male to female ratio was 1.5. 13 patients (52%) had limited stages (I + II), 12 patients (48%) had advanced disease (stage III + IV). 21 patients received the COPBLAM/IMVP-16 regimen. Two patients received more intensive treatments; two received less intensive therapy. Complete remissions were achieved in 16/25 patients (64%). The median observation time of surviving patients was 30 months (range 5-72 months). The actuarial overall survival and event-free survival at 2 years of 21 patients receiving COPBLAM/IMVP-16 were 69% and 35%, respectively. Intensive chemotherapy led to complete remissions in about 60% of the patients and to long-term disease-free survival for one-third. The observed clinical courses illustrate the aggressive nature of PSC, LEL and TZL.     

Survival in conventionally treated younger (<60 years) multiple myeloma patients: no improvement during two decades. Nordic Myeloma Study Group (NMSG)

The patient registers of five prospective population based Nordic studies were reviewed for patients <60 yr. A total of 313 patients with symptomatic multiple myeloma were identified. Thirty-nine of them were judged retrospectively to have been ineligible for intensive chemotherapy regimens. The remaining 274 patients were considered appropriate as a historical control group for comparison with patients treated with high-dose chemotherapy and autologous stem cell support. Of these, 32 had been diagnosed during the period 1970-83, 101 during the period 1984-89 and 141 during the period 1990-92. The median age was 54 yr. Six percent were Durie/Salmon stage I, 38% stage II and 56% stage III. Melphalan-prednisone was used for initial therapy in 87%. Median survival for all patients with symptomatic myeloma was found to be 41 months, and for those selected for the control group 44 months, with no noted differences between the aforementioned diagnostic periods. We conclude that the expected median survival is 44 months for myeloma patients <60 yr who may be considered for high-dose therapy protocols. New developments in chemotherapy and supportive therapy, achieved during the two decades which preceded the use of high-dose chemotherapy with stem cell rescue, have not changed the overall prognosis in multiple myeloma.     

Outcome of older critically ill patients: a matched cohort study

BACKGROUND: Admission of older patients to intensive care units is a controversial issue. OBJECTIVE: To estimate age-associated mortality of critically ill patients. METHODS: A prospective matched cohort study in the Medical-Surgical Intensive Care Unit of a tertiary hospital was conducted. We included 100 consecutive patients older than 70 years admitted to the intensive care unit (cases) and 100 patients younger than 70 years (controls). The matching criterion was the severity of illness at admission to the intensive care unit as estimated by the simplified acute physiological score (SAPS II) without including age in its calculation. RESULTS: Mortality in the intensive care unit was higher, but not statistically significant, in the older group: 26% vs. 19% (p = 0.23). Patients older than 70 years had a longer duration of mechanical ventilation (median 7 vs. 3 days) and longer stay in the intensive care unit (median 8 vs. 5 days). There were no differences in organ dysfunctions, except for a higher incidence of respiratory failure in the older group (p < 0.001). The use of invasive procedures was similar in both groups. There were more orders for the withholding/withdrawal of treatment in patients older than 70 years (9 vs. 3%, p = 0.07). CONCLUSION: In our study, age was not related with a significant higher mortality. In the older patients included in our study the survival was greater than 70% with a similar resource utilization except for a longer stay in the intensive care unit.     

Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.-Canadian multicenter study

BACKGROUND/AIMS: HIV-infected patients now live longer and often have complications of liver disease, especially with hepatitis B or C virus coinfection. Limited data are available on those with hepatocellular carcinoma (HCC). METHODS: A retrospective analysis from 1992 to 2005 in 6 centers identified 63 HIV-infected HCC patients. Controls were 226 consecutive HIV-negative HCC patients from four sites. RESULTS: HIV-positive patients were younger than controls (52 vs. 64 years, p<0.001), more commonly had chronic hepatitis B or C (97% vs. 73%, p<0.001), were more frequently symptomatic (51% vs. 38%, p=0.048), had a higher median alfa-fetoprotein level (227 vs. 51 ng/ml, p=0.005), but a similar mean Child-Turcotte-Pugh score (7.0 vs. 7.5, p=0.05) and HCC staging score (Barcelona-Clínic-Liver-Cancer stages C+D in 50% vs. 58%, p=0.24). HCC developed faster in HIV/HCV-coinfected than in HCV-monoinfected patients (mean, 26 vs. 34 years after HCV infection, p=0.002). HIV-positive patients received proven therapy more often (48% vs. 31%, p=0.017), but median survival was similar (6.9 vs. 7.5 months, p=0.44). Independent factors predicting survival were symptomatic presentation (hazard ratio [HR], 0.437; p<0.001), any proven therapy (HR, 2.19; p<0.001), diagnosis after 01-Jan-2002 (HR, 1.52; p=0.010), Barcelona-Clínic-Liver-Cancer stages C+D (HR, 0.491; p<0.001), AST/ALT >or= 2.00 (HR, 0.597; p=0.001), AFP >or= 400 ng/mL (HR, 0.55, p=0.003), and platelets >or= 100,000/mm3 (HR, 0.651; p=0.012), but not HIV-serostatus (p=0.19). In HIV-infected patients without HCC therapy (n=33), median survival was longer with undetectable HIV RNA (<400 copies/mL) than with HIV viremia (6.5 vs. 2.6 months, p=0.013). CONCLUSIONS: HIV-positive HCC patients are younger and more frequently symptomatic and infected with HCV or HBV than HIV-negative patients. Tumor staging and survival are similar. In untreated patients, undetectable HIV RNA independently predicts better survival.     

Efficacy of early reperfusion therapy at the acute stage of myocardial infarction in elderly patients: the USIK database

The role of early reperfusion therapy at the acute stage of myocardial infarctus in elderly patients is debated. The aim of this study was to analyze the prognostic role of reperfusion with i.v. thrombolysis or primary PTCA in the nationwide USIK database, which prospectively included all pts admitted to a CCU for an AMI < 48 hours in France in November 1998. For the purpose of the present study, only patients admitted within 24 hours of AMI and with one-year follow-up available were included. Of the 1838 patients included, 785 were > 70 years-old, of whom 225 (29%) had early reperfusion therapy with thrombolysis (N = 173) or primary PTCA (N = 52). Patients treated with early reperfusion had a baseline profile that differed substantially from that of patients treated conventionally: women (31% vs 50%, p < 0.001), admission within six hours of symptom onset (84% vs 55%, p < 0.001), history of systemic hypertension (48% vs 60%, p < 0.002), stroke (5% vs 11%, p < 0.01), peripheral arterial disease (8% vs 18%, p < 0.001); congestive heart failure (5% vs 20%, p < 0.001) or previous MI (12% vs 25%, p < 0.001), more anterior location of current MI (40% vs 28%, p < 0.002). Overall one-year Kaplan-Meier survival was 78% for patients with versus 64% for those without reperfusion therapy (p < 0.01). In patients with Q wave myocardial infarction, Cox multivariate analysis showed that reperfusion therapy was an independent predictor of survival (RR 0.66; 95% Confidence Interval: 0.45-0.96), along with age, anterior location and history of congestive heart failure. Therefore, data from this large "real life" registry indicate that reperfusion therapy with either thrombolysis or primary PTCA is associated with improved one-year survival in patients over 70 years of age.     

Prognosis of older patients with acute myeloid leukemia receiving either induction or noncurative treatment: a single-center retrospective study

Since few studies focus on prognostic factors in unselected elderly acute myeloid leukemia (AML) patients, a retrospective analysis of 138 consecutive patients aged >55 years (median age: 67, range: 56-89) with AML diagnosed at a single center over an 8-year period was performed: 69% had de novo AML and 31% secondary (s) AML; 67% of the patients were karyotyped. Of the patients, 73 (53%) were treated with standard induction therapy protocols and 65 (47%) received palliative treatment only. Univariate and multivariate analyses of the effects of the following factors on overall survival (OS) were performed: sex, age > or = vs <65 years, de novo vs sAML, serum (s) lactate dehydrogenase (LDH) > or = vs <400 U/l, leukocytes > or = vs <50,000/ microl, induction therapy, and karyotype. Additionally, in patients receiving induction therapy, complete remission (CR) rates and survival from CR were analyzed. CR rate was 47% [95% confidence interval (35%, 59%)], 53% (39%, 66%) in de novo AML, and 21% (5%, 51%) in sAML. After a median follow-up of 4 years, 130 deaths were observed (94%). In a univariate analysis, significant factors for longer OS were induction therapy, age <65 years, sLDH <400 U/l, and de novo AML. In a multivariate analysis, significant factors for longer OS were sLDH <400 U/l and induction therapy. However, the difference between treatment outcome may also be due to selection criteria not captured, such as performance status, comorbid conditions, wish of the patient, etc. The effects of intensive and nonintensive treatment in this patient group need to be investigated in prospective, randomized trials in which these clinical parameters of high relevance for treatment decisions in older patients are also considered.     

Does systematic 2‐field lymphadenectomy for esophageal malignancy offer a survival advantage? Results from 178 consecutive patients

SUMMARY. More extensive resection for esophageal cancer has been reported to improve survival in several series. We compared results from an unselected consecutive cohort of patients undergoing radical esophagectomy, including removal of all periesophageal tissue with a 2‐field abdominal and mediastinal lymphadenectomy for esophageal and gastroesophageal malignancy. A prospective electronic database was reviewed for patients with esophageal malignancy undergoing an open esophagectomy between 1991 and 2004. Data were analyzed on an SPSS file (version 12.0, Chicago, IL, USA) using χ² or Fisher's exact test; odds ratio and 95% confidence interval; and the Kaplan–Meier method, log–rank test and Cox's proportional hazards regression for survival analysis. There were 178 patients with a median age of 65 years and a 70/30 male to female ratio. Median follow‐up was 20.4 months. Pathology comprised adenocarcinoma in 64% of patients, squamous cell carcinoma 30%, and other malignancies 6%. Seventeen patients had neoadjuvant therapy. Hospital mortality was 3.3%. Complete resection was achieved in 87%. Local recurrence occurred at a median of 13 months in 6.7% of patients. Overall 5‐year survival was 42%. For patients with invasive squamous cell carcinoma and adenocarcinoma the 5‐year survival was 47% and 40.3%, respectively, and for patients without nodal involvement it was 71.5%, with one to four nodes involved, 23.5% and with >4 nodes, 5% (P < 0.001). Survival decreased with increasing direct tumor spread (P < 0.001) and pathological stage (P < 0.001). Esophageal resection with systematic 2‐field lymphadenectomy can be performed with acceptable operative mortality and favorable survival.     

Results of therapy in adult acute nonlymphoblastic leukemia: experience in Jerusalem, Israel, during 1975-1982

78 previously untreated patients (aged 16-82 years) with acute nonlymphoblastic leukemia received intensive chemotherapy for induction of remission. In 64 patients, the combination used consisted of daunomycin and cytosine arabinoside with or without 6-thioguanine. The overall remission rate was 59 and 87% for those who received what was considered as adequate therapy. Patients who achieved remission received maintenance and, in part, late intensification. The median duration of remission was 9 months. The median survival of the patients who attained remission was 24 months, compared to 15 months for the entire patient group and 3 months for patients who failed to achieve remission. Age had no effect on the rate and duration of the remission obtained but the median survival was significantly longer in patients below the age of 50 years.     

The role of intensive remission induction and consolidation therapy in patients with acute myeloid leukaemia

Sixty-one patients with AML, 59 adults and two children, were treated with intensive remission induction and consolidation therapy. The median age was 36 years. Forty-four (72%) patients entered complete remission (CR); 11 patients received a bone marrow transplantation. The median survival of complete remitters was 26.5 months; the probability of remaining in CR at respectively 1 and 2 years was 75% and 62%. The only factor significantly correlated with the outcome of remission induction, survival and duration of CR was age. Patients less than 30 years fared significantly better than those 30 years or older; no difference in outcome was observed between patients aged 30-50 and those over 50 years. In patients less than 30 years the CR rate was 95%; 75% of them were still alive at 2 years and only one (5%) has relapsed. In contrast, in patients 30 years or older the CR rate was 60% and the median survival only 11.5 months, 50% of the complete remitters in this age group have relapsed. Morbidity from intensive consolidation therapy was considerable; more than 50% of consolidation courses were complicated by high fever, needing urgent admission; only four (3%) courses had a fatal event. It is concluded that intensive consolidation therapy may be considered as a major advance in the treatment of younger patients with AML, while its role in older individuals remains questionable. A possible explanation for the completely different outcome in younger and older patients with AML is discussed.     

Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients

The clinical significance of complex chromosome aberrations for adults with acute myeloid leukaemia (AML) was assessed in 920 patients with de novo AML who were karyotyped and treated within the German AML Cooperative Group (AMLCG) trials. Complex chromosome aberrations were defined as three or more numerical and/or structural chromosome aberrations excluding translocations t(8;21)(q22;q22), t(15;17)(q22;q11-q12) and inv(16)(p13q22). Complex chromosome anomalies were detected in 10% of all cases with a significantly higher incidence in patients > or = 60 years of age (17.8% vs. 7.8%, P < 0.0001). Clinical follow-up data were available for 90 patients. Forty-five patients were < 60 years of age and were randomly assigned to double induction therapy with either TAD-TAD [thioguanine, daunorubicin, cytosine arabinoside (AraC)] or TAD-HAM (high-dose AraC, mitoxantrone). Twenty-one patients achieved complete remission (CR) (47%), 20 patients (44%) were non-responders and 9% of patients died during aplasia (early death). The median overall survival (OS) was 7 months and the OS rate at 3 years was 12%. Patients receiving TAD-HAM showed a significantly higher CR rate than patients receiving TAD-TAD (56% vs. 23%, P = 0.04). Median event-free survival was less than 1 month in the TAD-TAD group and 2 months in the TAD-HAM group, respectively (P = 0.04), with a median OS of 4.5 months vs. 7.6 months (P = 0.13) and an OS after 3 years of 7.6% vs. 19.6%. Forty-five patients were > or = 60 years of age: 28 of these patient were treated for induction using one or two TAD courses and 17 cases received TAD-HAM with an age-adjusted reduction of the AraC dose. The CR rate was 44%, 38% were non-responders and 18% experienced early death. The median OS was 8 months and the OS rate at 3 years was 6%. In conclusion, complex chromosome aberrations in de novo AML predicted a dismal outcome, even when patients were treated with intensive chemotherapy. Patients under the age of 60 years with complex aberrant karyotypes may benefit from HAM treatment during induction. However, long-term survival rates are low and alternative treatment strategies for remission induction and consolidation are urgently needed.     

Receipt of maintenance therapy is most predictive of survival in older acute lymphoblastic leukemia patients treated with intensive induction chemotherapy regimens

While the prognosis for older adults diagnosed with acute lymphoblastic leukemia (ALL) is frequently poor, long‐term survival can be achieved in patients treated with curative intent. We reviewed the outcomes of 37 patients age ≥60 treated at our institution with either DVP‐ or hyperCVAD‐based chemotherapy regimens from 2003–2011. In this patient population, a complete response rate of 92%, relapse rate of 56% and median overall survival of 18.1 months was experienced. Univariate analysis revealed that receipt of maintenance therapy vs. no maintenance therapy was associated with a statistically‐significant impact on overall survival (p = 0.001, HR 0.15 for death), while disease‐related characteristics including high‐risk white blood cell count at diagnosis and Philadelphia chromosome status as well as treatment‐related factors including chemotherapy regimen or completion of intensive therapy were not. Many patients were unable to initiate or remain on maintenance therapy due to toxicities including infections and cytopenias. Our analysis reveals the benefit of prolonged therapy in the treatment of older adults with ALL as well as the high incidence of treatment‐related toxicity experienced by these patients. Am. J. Hematol. 88:657–660, 2013. © 2013 Wiley Periodicals, Inc.