Intensive chemotherapy in aggressive lymphomas: updated results of LNH- 80 protocol and prognostic factors affecting response and survival

One hundred patients with aggressive malignant lymphomas treated with the LNH-80 regimen were evaluated for long-term survival and pretreatment characteristics predictive of response and survival. LNH- 80 consists of three intensive courses of adriamycin cyclophosphamide vindesine bleomycin (ACVB) followed by sequential consolidation and final intensification. Eighty-four patients went into complete remission (CR), eight had a partial response (PR), three failed to respond, and five died during induction. Twenty-three patients (27%) relapsed, in two of whom a prolonged second remission was obtained. Sixty-three patients are currently alive, two of them with disease. Four patients died in CR. Median survival and median freedom from relapse survival were not reached with a median follow-up of 4 1/2 years. Characteristics negatively associated with response in multivariate analysis were: poor performance status, bone marrow involvement, and two or more extranodal sites of disease. Duration of CR was associated with splenic involvement. Three characteristics were negatively associated with survival in multivariate analysis: age, high grade subtypes, and bone marrow involvement.     

Efficacy and prognosis of chronic myeloid leukemia treated with imatinib mesylate in a Chinese population

There is limited data from developing countries on the current status of imatinib treatment for chronic myeloid leukemia (CML), thus we retrospectively analyzed 116 Chinese CML patients who received imatinib between 2003 and 2008. The response rates for 102 patients in chronic phase were: complete hematologic, 94.1%; complete cytogenetic, 69.6%; and complete molecular response, 54.9%. For 14 patients in the accelerated phase, the respective response rates were 85.7, 35.7 and 28.6%. The 3-year progression-free survival and 5-year overall survival were 73.3 and 74.8%. Although skin hypopigmentation occurs as the most common side effect (77.6%), imatinib is still well tolerated. In addition to the known pretreatment characteristics of spleen size, leukocyte and platelet counts, disease phase and Sokal scores, we found that delayed therapy, variant Philadelphia chromosome translocations and IM-related grade 3/4 leucopenia were associated with an inferior cytogenetic response. Four factors emerged as predictors of disease progression: molecular response, cytogenetic response, disease phase and disease duration prior to imatinib treatment, but only the latter three remained significant after multivariate analysis. The results indicate that the suboptimal outcome in Chinese patients is associated with delayed imatinib therapy, so the importance of the optimal treatment opportunity for CML should be emphasized.     

Prognostic factors in small cell carcinoma of the lung: a cancer and leukemia group B study

Prognostic factors were studied in 224 patients with small cell carcinoma of the lung entered in a Cancer and Leukemia Group B protocol. Extent of disease was the major predictor of complete remission (CR) frequency and survival greater than 2 years, with CR rates being 40% for patients with limited disease (LD) and 10% for those with extensive disease. Patients who were classified as having extensive disease on the basis of isotope scan evidence of a single bone metastasis had survival characteristics and response rates similar to those of patient with LD. A multivariate analysis of various factors, which may influence overall survival, reveals a good-risk population to be defined as having LD and an initial performance status less than or equal to 2, with or without a single metastatic focus on bone scan. Furthermore, this risk definition fairly successfully predicted which patients had the greatest chance of achieving a CR (45%). Age less than 70 years was shown to be a significantly adverse factor on survival in these multivariate analyses after adjusting for risk. When long-term survivors (less than 24 months) were investigated by multivariate analyses, the new risk system was found to be the only significant pretreatment factor. Interestingly, sex was the next marginally influential factor on long-term survival. Future stratification by these risk categories should lead to more homogeneous subgroups for comparison of different therapeutic approaches and should provide some indication as to how much better the newer treatment program is within each risk group.     

Prognostic value of serum M-protein doubling time at escape from plateau of multiple myeloma

Abstract: A long plateau phase is one of the strongest signs predicting long survival in multiple myeloma. The kinetics of escape from the plateau is, however, poorly known, and so is its influence on subsequent survival. During a 9-yr follow-up of 432 myeloma patients the serum M-protein doubling time at first relapse was measured from serial observations in 137 cases. Univariate and multivariate analyses of pretreatment characteristics and of characteristics associated with chemotherapy were used to identify the predictors influencing on M-protein doubling time. In 65 patients the M-protein doubling time was 6 months or less and in 72 longer, with median remaining survival times of 17 and 45 months, respectively; 50% of the former group had any response to salvage chemotherapy, compared to 75% of the latter group. In univariate analysis stage and Hb were significant predictors for the M-protein doubling time. An at least 75% response was associated with short doubling time. However, the multivariate analysis left only a long preceding plateau and use of several drug combinations during primary chemotherapy as significant predictors for a long M-protein doubling time. A M-protein doubling time of 6 months or less is associated with frequent resistance to salvage chemotherapy and short remaining survival. A short doubling of the M-protein is preceded by a short plateau. The use of several drug combinations during primary chemotherapy does not jeopardize the later course of the disease. A short M-protein doubling time seems not be a chemotherapy induced phenomenon.     

Factors associated with humoral response to ESAT-6, 38 kDa and 14 kDa in patients with a spectrum of tuberculosis.

SETTING: Tertiary care chest hospital in Montreal, Canada, where the average annual incidence of TB is 10/100,000 population. OBJECTIVES: To evaluate the clinical correlates of humoral response to three Mycobacterium tuberculosis antigens. METHODS: Humoral response to three M. tuberculosis antigens, 38 kDa, 14 kDa and ESAT-6, was measured with ELISA in patients with a spectrum of TB-related conditions. The association of positive tests for each antigen, defined with receiver operator characteristics (ROC) analysis, and patient characteristics was assessed in multivariate regression. RESULTS: A total of 383 patients underwent serologic testing. In multivariate analysis, humoral response to 38 kDa was associated with active disease, response to 14 kDa was associated with inactive TB and female sex, and response to ESAT-6 with inactive TB, female sex, prior contact with TB, and recent arrival in Canada from high prevalence countries. CONCLUSIONS: Response to the 38 kDa antigen was associated with current active disease, and was very different from response to the 14 kDa and ESAT-6 antigens. These latter two antigens were associated with risk factors for future active, but not current disease, suggesting that they might be useful to identify persons with higher risk of reactivation of latent TB.     

Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: comparison with bone marrow transplantation

The outcome of 155 adult aplastic anemia (AA) patients treated with antithymocyte globulin (ATG, Upjohn, Kalamazoo, MI) at University of California, Los Angeles from 1977 to 1988 was evaluated. The median survival of the 146 patients who did not undergo bone marrow transplantation was 5.6 years, with 49% +/- 4% surviving more than 6 years. The most important predictor of survival was positive response to ATG (P < 0.001), which was observed in 48% of patients. Among pretreatment variables, disease severity was the best predictor of survival. Patients with moderate AA (MAA) had significantly better survival than those with severe (SAA) or very severe (VSAA) disease (P = 0.04). The 6-year actuarial survival rates of the three groups were 71% +/- 9%, 48% +/- 7% and 38% +/- 7%, respectively. Cox regression analysis found disease severity to be the only pretreatment variable significantly associated with survival (P = .02). Patient age, sex, disease etiology, concurrent treatment with androgens, or duration of ATG therapy were not associated with differences in survival or response to ATG. Late clonal hematologic complications (ie, myelodysplasia, acute myelogenous leukemia) were observed in 5 of the 77 patients followed for more than 2 years after ATG treatment. In addition, one case of non-Hodgkin's lymphoma and three solid tumors occurred in the ATG-treated patients. The survival of 56 ATG-treated patients with SAA or VSAA between the ages of 16 and 43 did not differ significantly from that of 55 adult AA patients who underwent bone marrow transplant (BMT) during the same time period (P = 0.6). However, 6-year survival rates improved from 43% for patients transplanted before 1984, to 72% for those who underwent BMT between 1984 and 1989. In contrast, there was no difference in the survival rates of patients treated with ATG during these two time periods (46% v 45%, respectively). The results suggest a superior long-term outcome for adult patients with SAA treated with BMT rather than with ATG alone, using current protocols.     

Prognostic value of lung function and pulmonary haemodynamics in OSA patients treated with CPAP.

The aim of the present study was to determine survival rates of obstructive sleep apnoea patients treated with continuous positive airway pressure (CPAP) and to investigate the prognostic value of pretreatment lung function and pulmonary haemodynamics. Two hundred and ninety-six patients, exhibiting > or = 20 apnoeas plus hypopnoeas per hour of sleep, were included. Patients were treated with nasal CPAP and regularly followed up. The cumulative survival rates were 0.96 (95% confidence interval (CI): 0.94-0.99) at 3 yrs and 0.93 (95% CI: 0.91-0.97) at 5 yrs. Most patients died from cardiovascular disease. Apart from age, covariates associated with a lower survival were the presence of a heavy smoking history, a low vital capacity, a low forced expiratory volume in one second (FEV1) and a high mean pulmonary artery pressure. Only three covariates were included by forward stepwise selection in the multivariate analysis, smoking habit (>30 pack-yrs), age and FEV1. The observed survival rates of the group as a whole were similar to those of the general population matched in terms of age, sex and smoking habit, except for patients between 50 and 60 yrs old who had reduced survival. This difference disappeared when patients of the present study with an associated chronic obstructive pulmonary disease were excluded from the comparison. In conclusion, survival of obstructive sleep apnoea patients treated with nasal continuous positive airway pressure is near to that of the general population. The prognosis is worse in subgroups of patients with a history of heavy smoking and with an associated chronic obstructive pulmonary disease.     

Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia

Early results of the fludarabine, cyclophosphamide, and rituximab (FCR) regimen in 224 patients showed that it was highly active as initial therapy of chronic lymphocytic leukemia. In this report, we present the final results of all 300 study patients at a median follow up of 6 years. The overall response rate was 95%, with complete remission in 72%, nodular partial remission in 10%, partial remission due to cytopenia in 7%, and partial remission due to residual disease in 6%. Two patients (< 1%) died within 3 months of starting therapy. Six-year overall and failure-free survival were 77% and 51%, respectively. Median time to progression was 80 months. Pretreatment characteristics independently associated with inferior response were age 70 years or older, beta2-microglobulin twice the upper limit of normal (2N) or more, white cell count 150 x 10(9)/L or more, abnormal chromosome 17, and lactate dehydrogenase 2N or more. No pretreatment characteristic was independently associated with decreased complete remission duration. The risk of late infection was 10% and 4% for the first and second years of remission, respectively, and less than 1.5% per year for the third year onward. In a multivariate analysis of patients receiving fludarabine-based therapy at our center, FCR therapy emerged as the strongest independent determinant of survival.     

Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease

Several studies have focused on investigation of the optimal salvage regimen to induce maximum response before autologous stem cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin's disease (HD). However, in most of these studies, the follow-up is relatively short. In the present study, we report on long-term results of 55 consecutive patients with HD who received Mini-BEAM [BCNU (carmustine), etoposide, cytarabine, melphalan] as salvage therapy before ASCT. Eleven patients were refractory to front-line therapy, 17 were partial responders, and 27 patients had relapsed from HD. Twenty-eight patients achieved complete response, and 18 achieved partial response with a median of two cycles of Mini-BEAM, giving a total response rate of 84%. Significant factors predicting poor response (P < 0.05) were: initial treatment with MOPP (mechloroethamine, oncovin, procarbazine, prednisolone), > or = two previous chemotherapy regimens and three disease characteristics at Mini-BEAM treatment: presence of B symptoms, extranodal involvement or low serum albumin. However, only the last two factors retained independent influence on multivariate analysis. In total, 45/55 patients have been transplanted. Median follow-up after Mini-BEAM administration for living patients is 68 months. At the time of reporting, 31 out of 55 patients (56.4%) are still alive, 21 patients (38%) have relapsed, three (5.4%) have developed secondary neoplasias, and five have died of other complications not related to disease progression. The actuarial 7-year overall survival (OS) was 52%, the progression-free survival (PFS) 54% and the event-free survival (EFS) 36%. The response to Mini-BEAM was the most important prognostic factor for predicting the long-term probability of surviving the disease: none of the eight patients who did not respond to Mini-BEAM were alive at 3 years. On multivariate analysis, response to Mini-BEAM and extranodal involvement before Mini-BEAM had a significant influence on OS. Our results show the safety and efficacy of Mini-BEAM before ASCT for refractory or relapsed HD patients.     

Factors predicting survival in adults with stage I and II large-cell lymphoma treated with primary radiation therapy

The records of 148 consecutive patients with Ann Arbor stage I and II large-cell lymphoma treated with primary radiation therapy with or without adjuvant chemotherapy were analyzed retrospectively for pretreatment prognostic variables and results of treatment. For patients treated with radiation to fields on one side of the diaphragm, the 5 year freedom-from-relapse rate was 25% and the survival rate was 35%, but for those given additional transdiaphragmatic radiation or for those given radiation plus adjuvant chemotherapy, the rates were both approximately 67%. In a multivariate analysis, the only significant pretreatment prognostic variables were the number of sites of involvement and bulk of disease, with relapse as the endpoint. For patients treated with radiation to both sides of the diaphragm or with radiation plus adjuvant chemotherapy, the 5-year freedom-from-relapse rate was 82% for the group with a favorable prognosis (with less than three sites of involvement and a mass size of less than 10 cm) and 55% for those with an unfavorable prognosis.     

Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study.

The GIMEMA ALL 0288 trial was designed to evaluate the impact of a 7-day prednisone (PDN) pretreatment on complete remission (CR) achievement and length, the influence of the addition of cyclophosphamide (random I) to a conventional 4-drug induction on CR rate and duration, and whether an early post-CR intensification (random II) by an 8-drug consolidation could improve CR duration. Median follow-up of this study was 7.3 years. From January 1988 to April 1994, among 794 adult (> 12 but < 60 years) patients registered, 778 were eligible. Their median age was 27.5 years; 73% had B-lineage acute lymphoblastic leukemia (ALL) and 22% had T-lineage disease; 18% showed associated myeloid markers; 47 of 216 analyzed patients (22%) had Philadelphia chromosome-positive ALL. Response to PDN pretreatment was observed in 65% of cases. CR was achieved in 627 patients (82%). Resistant patients and induction death rates were 11% and 7%, respectively. Random II was applied to 388 patients with CR; 201 had maintenance alone and 187 had consolidation followed by maintenance. The relapse rate was 60%; isolated central nervous system relapses were 8% of all CRs and 13% of all relapses. Median survival (overall survival [OS]), continuous complete remission (CCR), and disease-free survival (DFS) were 2.2, 2.4, and 2 years, respectively. PDN pretreatment response resulted the main independent factor influencing CR achievement, OS, CCR, and DFS; the addition of cyclophosphamide in induction significantly influenced CR achievement in a multivariate analysis. Neither induction intensification nor early consolidation appeared to influence CCR and DFS duration. For the first time PDN pretreatment response proved to be a powerful factor predicting disease outcome in adult ALL patients.     

Prognostic significance of elevated serum beta 2-microglobulin levels in adult acute lymphocytic leukemia.

PURPOSE: Elevated serum beta-2 microglobulin (beta 2M) levels are associated with poor prognosis in several lymphoproliferative disorders including multiple myeloma and lymphoma. Their prognostic relevance in acute lymphocytic leukemia (ALL) is unknown. We analyzed the associations of serum beta 2M levels at diagnosis with pretreatment characteristics and with prognosis in adult ALL. PATIENTS AND METHODS: One hundred fifty-nine adults with newly diagnosed ALL were investigated. Serum beta 2M levels were determined at diagnosis, on fresh peripheral blood samples, using a radioimmunoassay, the Pharmacia beta 2 Micro RIA (Pharmacia Diagnostics, Uppsala, Sweden). Statistical correlations were assessed by standard methods, and further independent prognostic value of serum beta 2M was determined by multivariate analysis. RESULTS: Patients with beta 2M levels of 4.0 mg/L or above had a lower complete response rate (61% versus 80%; p = 0.02), a significantly worse survival (p < 0.01), and a significantly higher association with development of central nervous system (CNS) leukemia (p < 0.01). High beta 2M levels were more common among patients with older age, with elevated creatinine, bilirubin, and alkaline phosphatase levels, with low albumin levels, and with B-cell disease. Multivariate analysis for survival indicated the beta 2M level to be an independent prognostic variable (after adjusting for pretreatment creatinine level and age). The evaluation of beta 2M levels within low- and high-risk groups for CNS disease suggested an association of elevated beta 2M levels with a worse incidence of CNS disease in the high-risk patients. CONCLUSION: Monitoring serum beta 2M levels may provide significant prognostic information in adults with ALL and should be included in their pretreatment evaluation. Its importance in childhood ALL requires investigation.     

Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML

CD33 is expressed on the majority of acute myeloid leukemia (AML) leukemic blasts and is the target for gemtuzumab ozogamicin (GO), a toxin-conjugated anti-CD33 mAb. In the present study, we quantified the CD33 mean fluorescent intensity of leukemic blasts prospectively in 619 de novo pediatric AML patients enrolled in Children's Oncology Group GO-containing clinical trials and determined its correlation with disease characteristics and clinical outcome. CD33 expression varied more than 2-log fold; a median mean fluorescent intensity of 129 (range, 3-1550.07) was observed. Patients were divided into 4 quartiles, quartiles 1-4 (Q1-4) based on expression and disease characteristics and clinical response defined across quartiles. High CD33 expression was associated with high-risk FLT3/ITD mutations (P < .001) and was inversely associated with low-risk disease (P < .001). Complete remission (CR) rates were similar, but patients in Q4 had significantly lower overall survival (57% ± 16% vs 77% ± 7%, P = .002) and disease-free survival from CR (44% ± 16% vs 62% ± 8%, P = .022). In a multivariate model, high CD33 expression remained a significant predictor of overall survival (P = .011) and disease-free survival (P = .038) from CR. Our findings suggest that CD33 expression is heterogeneous within de novo pediatric AML. High expression is associated with adverse disease features and is an independent predictor of inferior outcome. The correlation between CD33 expression and GO response is under investigation. These studies are registered at www.clinicaltrials.gov as NCT00070174 and NCT00372593.     

Prognostic value of the soluble interleukin-2 receptor level after patients with follicular lymphoma achieve a response to R-CHOP

Objectives: Follicular lymphoma (FL) is a clinically and biologically heterogeneous disease. Therefore, it is important to identify factors that can predict its clinical outcome.

Methods: We retrospectively evaluated the usefulness of soluble interleukin-2 receptor (sIL-2R) levels after R-CHOP (posttreatment sIL-2R) in 72 patients with newly diagnosed FL who had either a complete response (CR) or partial response. With the use of a recursive partitioning analysis, we determined the cut-off values of post- and pretreatment sIL-2R levels that were associated with disease progression, which corresponded to 486.5 and 5405?U/mL, respectively.

Results: The high posttreatment sIL-2R group showed a significantly inferior progression-free survival (PFS) compared to the low posttreatment sIL-2R group in all patients (3-year PFS 52.6% vs. 77.4%, P?=?0.003), and in patients with CR (3-year PFS 57.1% vs. 82.1%, P?=?0.034). Although a multivariate analysis showed that pretreatment sIL-2R, but not posttreatment sIL-2R, was an independently significant predictive factor for disease progression, among patients with low pretreatment sIL-2R levels, those with high posttreatment sIL-2R levels tended to have inferior PFS. There was a significant trend in PFS among the high pretreatment sIL-2R group, the low pre- and high posttreatment sIL-2R group, and the low pre- and low posttreatment sIL-2R group (P?Conclusion: Among patients with a low pretreatment sIL-2R level who exhibited a positive response to R-CHOP, the posttreatment sIL-2R level may help to identify those with a poor prognosis.     

Calreticulin expression in the clonal plasma cells of patients with systemic light-chain (AL-) amyloidosis is associated with response to high-dose melphalan

In high doses with stem-cell transplantation, melphalan is an effective but toxic therapy for patients with systemic light-chain (AL-) amyloidosis, a protein deposition and monoclonal plasma cell disease. Melphalan can eliminate the indolent clonal plasma cells that cause the disease, an achievement called a complete response. Such a response is usually associated with extended survival, while no response (a less than 50% reduction) is not. Gene-expression studies and a stringently supervised analysis identified calreticulin as having significantly higher expression in the pretreatment plasma cells of patients with systemic AL-amyloidosis who then had a complete response to high-dose melphalan. Calreticulin is a pleiotropic calcium-binding protein found in the endoplasmic reticulum and the nucleus whose overexpression is associated with increased sensitivity to apoptotic stimuli. Real-time PCR and immunohistochemical staining also showed that expression of calreticulin was higher in the plasma cells of those with a complete response. Furthermore, wild-type murine embryonic fibroblasts were significantly more sensitive to melphalan than calreticulin knock-out murine embryonic fibroblasts. These data have important implications for understanding the activity of melphalan in plasma-cell diseases and support further investigation of calreticulin and its modulation in patients with systemic AL-amyloidosis receiving high-dose melphalan.     

Incidence of response and long-term follow-up in patients with hairy cell leukemia treated with recombinant interferon alfa-2a [see comments]

Thirty-five evaluable patients with hairy cell leukemia (HCL) were treated with recombinant interferon alfa-2a (rIFN-alpha 2a), given at a dose of 3 X 10(6) units (U) intramuscularly (IM) daily for 6 months followed by 3 X 10(6) U IM three times a week for an additional 18 months in a single institution study. All treatment was stopped after 24 months. Sixty-nine percent of patients achieved a partial response, 11% a minor response, and 3% (one patient) had stable disease. Six patients (17%) did not respond to rIFN-alpha 2a. Two patients (6%) achieved a response but later progressed on treatment. A total of 23 patients completed 2 years of treatment and are evaluable for long-term follow-up at a median of 20 months postcompletion of therapy (range 9 to 32 months). Eleven patients (48%) have had progression of their disease at a median of 10 months (range .5 to 25 months) after treatment was discontinued. Statistical analysis of pretreatment patient characteristics did not reveal any factor(s) associated with a high probability of responding to rIFN-alpha 2a; however, analysis of post-treatment variables measured after 2 years of treatment suggested that a low platelet count was associated with a high rate of disease progression. These findings are compared with other published trials using rIFN-alpha 2b, a similar but not identical rIFN preparation. We conclude that while rIFN-alpha 2a has a high overall response incidence, the rate of disease progression after therapy is discontinued approaches 50%, and that a subset of patients can be identified who are at high risk for recurrence after completing 2 years of treatment.     

Long-term results of autologous stem cell transplantation for Hodgkin’s disease (HD) and low-/intermediate-grade B non-Hodgkin’s lymphoma (NHL): a report from the Austrian Stem Cell Transplantation Registry (ASCTR)

Between 1990 and 2001, 68 patients with advanced Hodgkin's disease (HD) and 86 patients classified as low-/intermediate-grade B non-Hodgkin's lymphoma (NHL) were reported to the Austrian Stem Cell Transplantation Registry (ASCTR). Following autologous stem cell transplantation (SCT) for HD, overall survival was 56% [95% confidence interval (CI): 40-72%] with a disease-/progression-free survival of 49%, reaching a plateau at 5 years. Using multivariate Cox regression analysis BEAM conditioning (carmustine, cytarabine, etoposide and melphalan) was predictive for favourable outcome, better disease-/progression-free survival and a significantly lower risk for relapse. The cumulative incidence of relapse was 30%, even for patients in complete remission at time of SCT. The cumulative risk for developing a secondary malignancy increased continuously over time, achieving 20% at 7 years and 46% at 10 years with previous radiotherapy as the only risk factor in the multivariate analysis. Overall survival for NHL patients was 45% (95% CI: 26-64%) with a disease-/progression-free survival of 26% at 7 years. In the multivariate Cox regression analysis stage of disease at time of SCT was the most powerful parameter for overall survival, disease-/progression-free survival and relapse. Mantle cell lymphoma, greater than or equal to three lines of previous therapy, and a conditioning regimen other than BEAM were also predictive for death. The main reason for treatment failure was relapse (cumulative incidence 54-75%). Because of the high risk of relapse/progression in both disease categories and the additional high rate of second malignancies in HD patients, allogeneic stem cells should be considered a valuable alternative for selected patients. The efficacy of allotransplantation following reduced-intensity conditioning should be tested in randomised trials.     

Outcome of adult severe or very severe aplastic anemia treated with immunosuppressive therapy compared with bone marrow transplantation: multicenter trial

To compare survival rates and long-term complications after bone marrow transplantation (BMT) or treatment with immunosuppressive agents (ISA) in the management of adult aplastic anemia (AA) and to identify prognostic factors associated with improved survival, we evaluated 229 adult AA patients treated with ISA from 1990 to 2001 and compared the results with those for 64 BMT recipients. Of 156 patients with severe aplastic anemia (SAA) or very severe AA treated with ISA (antithymocyte globulin [ATG] or ATG plus cyclosporine), 46.8% showed complete or partial response and 7.1% had relapses. After long-term follow-up, 1 case each of acute leukemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria developed. The 6-year survival rate was 69%. Response to ISA, disease severity, and low absolute neutrophil count (ANC) (< or = 200/mm3) were associated with poor survival. Patient age, sex, initial platelet count, etiology, or treatment regimen did not significantly affect survival. Cox regression analysis showed low ANC to be the only pretreatment variable significantly associated with poor survival (P = .000). Of 64 BMT recipients, 82.8% had sustained engraftment, and 12.5% experienced graft failure. Twenty (31.3%) of the patients developed grade II to IV acute graft-versus-host disease (GVHD), and 12 (18.8%) of the patients developed chronic GVHD. The 6-year survival rate was 79%. Patient age and sex, disease severity, etiology, ANC, initial platelet count, and treatment regimen did not affect survival. Survival of 83 AA patients, aged 14 to 40 years, treated with ISA was not statistically significant from that of 61 adult AA patients who underwent BMT (6-year survival rate, 65% and 79%, respectively). However, BMT in adult AA achieved long-term engraftment and a lower relapse rate than ISA. These results suggest that ISA can achieve a high response rate and long-term survival among patients with adult AA, regardless of disease severity. Further studies with larger numbers of patients and long-term follow-up are needed.     

High-dose therapy with autologous or allogeneic transplantation as salvage therapy for small cleaved cell lymphoma of follicular center cell origin

Between 1985 and 1996, 51 patients with relapsed or refractory small cleaved cell lymphoma (SCCL) received high-dose chemotherapy +/- TBI in conjunction with autologous (ABMT) (36 patients) or allogeneic transplantation (15 patients). Patients were eligible for ABMT if the bone marrow biopsy done prior to the planned transplant did not reveal microscopic involvement with SCCL. Patients receiving ABMT had a median age of 48 years, had received a median of 2.5 chemotherapy regimens prior to transplantation, and were transplanted a median of 35.5 months from diagnosis. Among patients receiving ABMT, 5 year actuarial survival was 56+/-11%. Median survival was 126+ months, and median survival from diagnosis was 191 months. Univariate and multivariate analysis identified sensitive disease as the best predictor of a favorable response. Five-year actuarial survival was 66+/-12% for patients with sensitive disease at the time of transplant as compared to 29+/-17% for patients with resistant disease, P = 0.015. Median survival in patients with sensitive disease at the time of ABMT was 126+ months. By univariate analysis, survival was significantly better for patients receiving ABMT as compared to patients receiving allogeneic transplants. Median survival following allogeneic transplantation was 5 months; 5 year actuarial survival was 15+/-13%. In a multivariate analysis, which considered autologous vs allogeneic transplantation, sensitive vs resistant disease, <3 vs > or = 3 prior treatments, and prior bone marrow involvement, allogeneic transplantation was significantly associated with poor survival. Treatment-related mortality occurred in eight of 15 patients receiving allogeneic transplantation and limited the effectiveness of this therapy. High-dose therapy in conjunction with ABMT is effective therapy for patients with SCCL whose disease is sensitive to chemotherapy and whose marrows are microscopically free of disease. Because of possible selection bias, it has not been proven that this approach increases survival in these patients. Treatment-related mortality limits the effectiveness of allogeneic transplantation in SCCL.     

Association of specific metastatic organs with the prognosis and chemotherapeutic response in patients with advanced lung cancer

BackgroundThis study was performed to investigate the influence of specific metastatic organs on the prognosis and therapeutic effect in patients with advanced lung cancer.MethodsWe retrospectively analyzed 400 patients with pathologically diagnosed advanced lung cancer to determine the association of the patients’ metastatic status with their prognoses and responses to first-line therapy. Metastases within the chest cavity (pulmonary metastasis, pleural effusion, and pericardial effusion) were counted as one organ.ResultsThe numbers of metastatic organs in the patients were as follows: one (n=199 patients), two (n=99), three (n=61), and four or more (n=41). A multivariate analysis showed that liver and muscle metastases were independently associated with shorter overall survival (median of 207 and 120 days, respectively) and shorter progression-free survival (median of 125 and 53 days, respectively). Chest cavity, bone, brain, and lymph node metastases were not associated with survival. The presence of either muscle or skin metastasis was associated with a lower response rate to first-line therapy than was the absence of each metastasis (14.3% vs. 49.4% and 11.1% vs. 48.9% in patients with vs. without muscle or skin metastasis, respectively).ConclusionsMuscle and liver metastases were associated with poor outcomes. Muscle and skin metastases were associated with a lower response rate to treatment. For patients with advanced lung cancer, oncologists should select treatment strategies considering the patients’ metastatic statuses as well as other clinical characteristics.