Survival Of Nonresponders Research Articles

Clinical Course of Nonresponders With Recurrent Focal Segmental Glomerulosclerosis After Pediatric Kidney Transplantation: A Retrospective Multicenter Study.

Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. Patients who do not achieve remission (nonresponders) have an especially poor graft survival. However, the characteristics that may affect graft survival in nonresponders are unknown. This study aimed to determine the clinical characteristics associated with graft survival in nonresponders. We retrospectively collected the clinical records of patients with FSGS and an age at onset <16 years who experienced posttransplant recurrence of FSGS at six hospitals in Japan from 1993 to 2018. Eight nonresponders with recurrent FSGS were enrolled in this study. The median time to recurrence after kidney transplantation was 1 day (interquartile range, 1-2 days). All patients received therapeutic plasma exchange and methylprednisolone pulse therapy. Rituximab was used as an add-on therapy in three patients. Five patients lost their graft within 2 years after kidney transplantation (rapid group). In contrast, three patients had much longer graft survival (nonrapid group). We compared the clinical characteristics of the rapid and nonrapid groups. Proteinuria tended to be lower in the nonrapid group at the third and subsequent months of therapy. The rapid group had persistent nephrotic syndrome. The rate of reduction in proteinuria was lower in the rapid group than in the nonrapid group. Our study suggests that persistent nephrotic syndrome and a low rate of reduction in proteinuria may predict rapid progression to graft failure in nonresponders.

ASO Visual Abstract: Three-Course Neoadjuvant Chemotherapy Associated with Unfavorable Survival in Non-responders to the First Two Courses for Locally Advanced Esophageal Cancer.

ASO Visual Abstract: Three-Course Neoadjuvant Chemotherapy Associated with Unfavorable Survival in Non-responders to the First Two Courses for Locally Advanced Esophageal Cancer.

The prognostic role of whole-body volumetric 68 GA-DOTATATE PET/computed tomography parameters in patients with gastroenteropancreatic neuroendocrine tumor treated with 177 LU-DOTATATE.

The aim of this study is to evaluate the prognostic role of Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and quantitative 68 Ga-DOTATATE PET/computed tomography parameters such as maximum standardized uptake value (SUVmax), mean SUV (SUVmean), DOTATATE tumor volume (DTV), total lesion DOTATATE (TLD) in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with 177 Lu-DOTATATE. Our retrospective study included 21 patients with GEP-NETs treated with 177 Lu-DOTATATE between January 2017 and January 2022. SUVmax, SUVmean, SUVmax/spleenSUVmax (SUVmax/Sx), DTV, TLD, SUVmean/spleenSUVmean (SUVmean/Sm), TLD/Sm values were calculated and recorded for all patients before and after 177 Lu-DOTATATE treatment. A total of 319 metastases were detected in the patients included in the study, and a total of 68 target lesions were selected. In univariant Cox regression analysis, TLD/Sm percent change (∆TLD/Sm) was found to be statistically significant on overall survival (OS) ( P = 0.044). The 3-year survival in nonresponders was 50% ( P = 0.034) based on ∆SUVmax/Sx values, 50% ( P = 0.002) based on RECIST values, 50% based on ∆TDTV + new lesion values ( P = 0.033), and according to ∆TTLD + new lesion values, it was 66% ( P = 0.030). In our study, we showed that SUVmax/Sx, RECIST, ∆TDTV + new lesion, and ∆TTLD + new lesion parameters can predict OS in the evaluation of response to treatment.

Siberian hamsters nonresponding to short photoperiod use fasting-induced torpor.

Nonresponding Siberian hamsters (Phodopus sungorus) do not develop the winter phenotype of white fur, low body mass (Mb) and spontaneous torpor in response to short photoperiod. However, their thermoregulatory response to fasting remains unknown. We measured body temperature and Mb of 12 nonresponders acclimated to short photoperiod and then to cold and fasted four times for 24 h. Four individuals used torpor, and in total, we recorded 19 torpor bouts, which were shallow, short and occurred at night. Moreover, fasting increased the heterothermy index in all hamsters. Low Mb was not a prerequisite for torpor use and Mb loss did not correlate with either heterothermy index or torpor use. This is the first evidence that individuals which do not develop the winter phenotype can use torpor or increase body temperature variability to face unpredictable, adverse environmental conditions. Despite the lack of seasonal changes, thermoregulatory adjustments may increase the probability of winter survival in nonresponders.

Clinical Outcome of Refractory Lymphoma Patients with Non Response to Chimeric Antigen Receptor T Cell Therapy

BackgroundChimeric antigen receptor T cell (CART) therapy has remarkably improved the outcome of patients (pts) with relapsed refractory B cell non-Hodgkin lymphoma. Anti-CD19 directed CART therapy have shown to yield durable remission in 40%-50% of patients with relapsed refractory (r/r) diffuse large B cell lymphoma (Neelapu et al. NEJM 2017; NCT 02348216). However, pts who had disease progression post CART therapy (non-responders) have poor outcomes. There is paucity of information regarding negative predictors for disease progression and outcome of non-responders post CART therapy.MethodsWe conducted a single center retrospective study of 11 patients with relapsed refractory large B cell lymphoma who underwent treatment with CART in our institution from December 2019 to June 2021 and further studied the baseline characteristics, and clinical outcome of 8 pts who were non responders to CART therapy.ResultsAll patients received low dose fludarabine cyclophosphamide based lymphodepleting conditioning regimen followed by anti-CD19 directed CART cells using CD28 as costimulatory domain with a target dose of 2 x 10 6 cells /kilogram of body weight.Baseline characteristics as shown in [Table 1]. Median age at CART therapy was 61 years (range 49-71). Median ECOG score at CART therapy was 1. All patients had chemo refractory disease at time of CART therapy with 9 patients having refractory diffuse large B cell lymphoma and 2 patients had transformed large B cell lymphoma. Genomic studies showed high risk disease in 4 patients with double hit lymphoma, 3 patients with complex cytogenetics with one having 17 p deletion and 2 patients with double expressors of c-myc and bcl2. Only 5 patients had available Ki-67 score > 80%. All patients had stage III-IV disease at the time of CART therapy. Seven pts had extra nodal disease and one patient had CNS involvement. Median R-IPI score at time of CART therapy was 3 (range 2-4). Median LDH, serum ferritin and serum CRP at the time of CART therapy was 388 (range 136-1489); 831 (range 116.9-1503); and 28.1 (range 7.4-226) respectively. Median number of prior therapies were 3 (range 2-9). One patient had prior autologous stem cell transplant. Median absolute lymphocyte count (ALC) and platelet count at CART therapy was 0.01/ul (range 0.01-2.5) and 89 x 10 3/ul (range 10-385) respectively. Median time from last salvage chemotherapy to CART therapy was 62 days (range 28-492).Total six pts had cytokine release syndrome (CRS) with median time for CRS onset was 3.5 days (range 1-8) with all of them having grade 1-2 CRS. Total seven pts had neurotoxicity with median time for onset was 5 days (range 1-41) post CART with 4 pts having > grade 3 immune effector cell associated neurotoxicity syndrome (ICANS). Overall, six and seven pts received tociluzumab and steroids respectively for treatment of CART related CRS and ICANS. Day 30 PET/CT scan showed three responders (2CR,1PR) and eight non responder patients with disease progression.Non responder pts to CART, when compared with responders had higher value of median LDH (438 vs 300; p = 0.92); median CRP (29 vs 13; p = 0.497) ; higher extra nodal involvement ( 6 pts vs one), median R-IPI score at the time of CART ( 4 vs 3), median number of prior therapies (4 vs 3), and median time from last salvage therapy to CART ( 73 days vs 50 days ; p = 0.91). No difference in baseline ALC count and platelet count was noted between the two groups. Compared to responders, non-responder pts had lower incidence of CRS (100% vs 37.5%) and ICANS (100% vs 50%). Post CART therapy, non-responder pts were treated with Nivolumab based immunotherapy in 5 pts, Ipilimumab based therapy in 1 pt, Selinexor in 1 patient and Polatuzumab based therapy in 2 pts.Median progression free survival and overall survival of non-responders was only 30.5 days and 94 days respectively. 5 out of 8 non responder pts died (4 due to disease progression and 1 due to sepsis). All three responder pts were alive and disease free at the end of study. Median follow up of our study was 108 days (range 32- 561).ConclusionsDespite smaller sample size, our study showed dismal outcome of pts who don't respond to CART therapy, showing an unmet need for better salvage therapies in such pts. Refractory lymphoma pts with extra nodal disease involvement, higher LDH and CRP at the time of CART therapy could be negative predictors for response. Further prospective studies with larger sample size required to further validate these findings. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001-2012.

The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti‐thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 (n = 492), or between 2009 and 2012 (n = 463). The median age of the patients was 21 years (range 1‐84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods (P = .007).The actuarial 10‐year survival for the entire population was 70%; transplant free survival was 64%. Predictors of survival in multivariate analysis, were severity of the disease, patients age and the interval between diagnosis and treatment. Survival was 87% vs 61% for responders at 6 months versus nonresponders (P < .0001). The 10‐year survival of nonresponders at 6 months, undergoing a subsequent transplant (n = 110), was 64%, vs 60% for patient not transplantated (n = 266) (P = .1). The cumulative incidence of response was 37%, 52%, 65% respectively, at 90, 180, and 365 days. In multivariate analysis, negative predictors of response at 6 months, were older age, longer interval diagnosis treatment, and greater severity of the disease. In conclusion, early mortality is low after first line treatment of AA with Thymoglobulin, and has been further reduced after year 2008. Patients age, together with interval diagnosis—treament and severity of the disease, remain strong predictors of response and survival.

Nonresponse to Interferon-α Based Treatment for Chronic Hepatitis C Infection Is Associated with Increased Hazard of Cirrhosis

BackgroundThe long-term consequences of unsuccessful interferon-α based hepatitis C treatment on liver disease progression and survival have not been fully explored.Methods and FindingsWe performed retrospective analyses to assess long-term clinical outcomes among treated and untreated patients with hepatitis C virus in two independent cohorts from a United States Veterans Affairs Medical Center and a University Teaching Hospital. Eligible patients underwent liver biopsy during consideration for interferon-α based treatment between 1992 and 2007. They were assessed for the probability of developing cirrhosis and of dying during follow-up using Cox proportional hazards models, stratified by pretreatment liver fibrosis stage and adjusted for known risk factors for cirrhosis and characteristics affecting treatment selection. The major predictor was a time-dependent covariate for treatment outcome among four patient groups: 1) patients with sustained virological response to treatment; 2) treatment relapsers; 3) treatment nonresponders; and 4) never treated patients. Treatment nonresponders in both cohorts had a statistically significantly increased hazard of cirrhosis compared to never treated patients, as stratified by pretreatment liver fibrosis stage and adjusted for clinical and psychosocial risk factors that disproportionately affect patients who were ineligible for treatment (Veterans Affairs HR = 2.35, CI 1.18–4.69, mean follow-up 10 years, and University Hospital HR = 5.90, CI 1.50–23.24, mean follow-up 7.7 years). Despite their increased risk for liver disease progression, the overall survival of nonresponders in both cohorts was not significantly different from that of never treated patients.ConclusionThese unexpected findings suggest that patients who receive interferon-α based therapies but fail to clear the hepatitis C virus may have an increased hazard of cirrhosis compared to untreated patients.

Preoperative therapy of esophagogastric cancer: the problem of nonresponding patients

Preoperative treatment is nowadays standard for locally advanced esophagogastric cancer in Europe. Surprisingly, little attention has been paid to nonresponders so far. The aim of our retrospective exploratory study was the comparison of responder, nonresponder, and primary resected patients in respect of outcome considering the tumor entity. From 2001-2011, 607 patients with locally advanced esophagogastric carcinoma (adenocarcinoma of the esophagogastric junction (AEG), n = 293; squamous cell cancer (SCC), n = 111; gastric cancer, n = 203) after preoperative treatment (n = 281) or primary resection (n = 326) were included. Histopathological response evaluation (Becker criteria) was available for 263. A total of 76/263 (28.9%) were responders (<10% residual tumor). There was an association of response with increased R0 resections (p < 0.001) but also with a higher complication rate (p = 0.008) compared to nonresponse and primary surgery. Mortality was not influenced. Increased R0 resections after response were confirmed in every tumor entity (AEG, p = 0.010; SCC, p = 0.023; gastric cancer, p = 0.006). Median survival was best for responders with 43.5months [95% confidence interval (CI), 27.9-59.1], followed by nonresponders with 24.3months (95% CI, 21.6-27.0) and primary resected patients with 20.8months (95% CI, 17.7-23.9; p = 0.002). AEG (p = 0.012) and gastric cancer (p = 0.017) revealed identical results, but in the subgroup of SCC, the survival of nonresponders (median, 11.6months; 95% CI, 6.9-16.3) was even worse than for primary resected patients (median, 23.8months; 95% CI, 1.7-46.0; p = 0.012). The histopathological response rate was low. Generally, nonresponding patients with AEG or gastric cancer seem not to have a disadvantage compared to primary resected patients, but nonresponders with SCC have a worse prognosis, which strengthens the demand for a critical patient selection in surgery for this tumor entity.

Assessment of Bone Marrow Fibrosis and Angiogenesis in Monitoring Patients With Multiple Myeloma

The aim of our study was to emphasize the importance of accurate and standardized techniques for detailed monitoring of the microenvironment in multiple myeloma (MM). Bone marrow fibrosis, angiogenesis, and plasma cell infiltrates in bone marrow biopsy (BMB) samples at the time of diagnosis and on completion of therapy were analyzed for 42 patients with newly diagnosed MM. Computerized image analysis was used for all slides stained with anti-CD138 and anti-CD34. The patients with fibrosis in pretreatment BMB samples had significantly higher microvessel density (MVD) and plasma cell infiltrates. In posttreatment BMB samples, nonresponders had a significantly higher frequency and grade of fibrosis and higher values of MVD, total vascular area, and plasma cell percentage. The overall survival of nonresponders and patients with increased marrow fibrosis in posttreatment BMB samples was significantly shorter. The obtained results confirm that complex morphologic examination of the bone marrow microenvironment during the monitoring of MM can provide better prognostic significance.

Azacitidine (AZA) After Failure of Lenalidomide (LEN) in Low/Int-1 Risk MDS with Del 5q

Abstract 2786 Background:LEN is currently the reference treatment of low/int 1 (lower) risk MDS with del 5q, yielding RBC transfusion independence (TI) in two thirds of the cases, with a median RBC-TI duration of 2.2 years. (MDS 003 trial, List, NEJM, 2006). In case of primary or secondary failure of LEN, however combined analysis of MDS 003 and MDS 004 trial showed prognosis to be unfavorable and treatment approaches uncertain. We report results of treatment with AZA in 13 lower risk MDS with del 5q with primary or secondary failure of LEN. Methods:The 13 cases were treated between November 2005 and June 2011 in 10 centers of the Groupe Francophone des Myelodysplasies (GFM). At onset of LEN, median age was 71 years, M/F 0.43, 7 patients (pts) had RAEB 1 and 6 RA, 11 had isolated del 5q and 2 had 1 additional chromosomal abnormality. IPSS was low in 6 and int 1 in 7 patients. The LEN dose was 5mg/d, 10mg/d 3 weeks/4weeks, 10mg/d in 8, 3 and 2 patients, respectively. 11 (85%) patients had achieved RBC-TI, for a median duration of 26.3m (range 5.8–57.3)(secondary failures), while 2 patients had not achieved RBC-TI (primary failures). At onset of AZA, 11 patients had progressed with a change in WHO category (RA to RAEB1, or RAEB 1 to RAEB2) in 8 patients, and/or acquisition of additional chromosomal abnormalities in 9 patients, 5 eventually having complex karyotype, of whom 2 had chromosome 17 abnormality leading to TP53 gene deletion (TP53 mutation analysis is in progress); IPSS was low (n=0), int 1 (n= 3), int 2 (n=2), high (n=8). Prior to onset of AZA, attempts had been made to increase the LEN dose from 5 to 10 mg/d in 2 patients, without success. Results:AZA was administered at the FDA/EMEA approved schedule (75mg/m2/dx7) in 12 pts, and reduced (5 day schedule) in 1 pt. The median number of cycles administered was 6 (range 1–23). Five patients (46%) achieved a response according to IWG 2006 criteria, including CR, PR, HI in 1, 0 and 4 pts respectively. All 5 responders achieved RBC –TI. 4 patients received less than 4 cycles of AZA: 2 stopped AZA after 1 cycle for hematological toxicity, 1 stopped after 3 cycles for progression, 1 pt died from septic shock after 3 cycles. Response duration was 2.9+, 4.4+, 6.2+, 13.8, and 24.6 months, respectively. No responder was allografted, but the age of responders was 68, 70, 78, 78 and 86 years, respectively. Median survival from onset of AZA was 8.8 m (range 0.8–24.9). The 5 responders were still alive 3+, 4.4+, 6.2+, 13.9+ and 24.8+ m after onset of AZA, while median survival in non-responders was 8.7 months. Among the 5 patients who responded to AZA, 4 had at onset of AZA a high IPSS, 3 had complex karyotype and 2 one additional chromosomal abn, while 4/5 had previously achieved RBC-TI with LEN (with a median duration of 26.1 months). Neither of the 2 patients with TP53 deletion responded to AZA. Finally, among the 2 primary failures to Lenalidomide, one achieved HI with AZA (of 4.4+ months duration) and the other died within 2 months. Conclusion:In this relatively small series almost 40% of the patients with lower risk MDS and del 5q who progressed under LEN could be salvaged by AZA, and might expect survival prolongation. The appearance of novel chromosomal abnormalities or complex karyotype at progression did not predict poor response to AZA, while we are currently analyzing the prognostic value of TP 53 mutations, which occur frequently at th at disease stage (Jadersten, JCO 2011), on response to AZA. Disclosures:Fenaux:Celgene: Honoraria, Research Funding.

Activity of Azacitidine (AZA) in Chronic Myelomonocytic Leukemeia (CMML)

Background: CMML is a distinct clinicopathologic entity recognized by the World Health Organization (WHO). Treatment of CMML by AZA was approved by the US Food and Drug Administration on the basis of a phase III randomized trial conducted by the Cancer and Leukemia Group B, for the treatment of myelodysplastic syndromes (MDS). Only 14 patients with CMML were included in the pivotal trial.Methods: We retrospectively reviewed our institutional experience of CMML treatment with AZA. 39 patients were treated between May 1996 and January 2006. AZA was given at 75 mg/m2 subcutaneously daily for seven days every 4 weeks or 100 mg/m2 daily for 5 days every 4 weeks. Patients who received at least 2 cycles of therapy were considered evaluable for response (N=34). All patients were evaluated for toxicity. The modified International Working Group standardized response criteria for MDS were used for evaluation. The response to AZA, duration of response, tolerability and survival are presented.Results: Patients had a median age of 68.5 years (range: 46–83); male: female ratio was 4.5:1. 28 patients (72%) had a WBC >12,000/μl (myeloproliferative form of CMML). 6 patients had 20–30% blasts in their bone marrow. The International Prognostic Scores were as follows: Low (N=3), Intermediate-1 (N=13), Internediate-2 (N=14), High (N=7), unknown in 2 patients (due to lack of aspirate particles in one and cytogenetics in the other). CMML was secondary to chemotherapy/radiotherapy in 5 patients. Overall response was seen in 14 patients (41%): 5 patients (15%) had a complete response (CR), 9 patients (26%) had hematologic improvement. Mean duration of response was 16.2 months (range: 3–50+); 2 patients are still alive and being treated with CR for >50 months. Average number of cycles to respond was 2.4 cycles (range: 1–6). Splenomegaly was present in 8 patients (20%). Treatment resulted in normalization of spleen size in 1 patient, decrease in 3 patients and no effect in 4 patients. Mean overall survival was 13.2 months (range 1–72). Average survival in responders was 23.5 months (5–72) while average survival in non-responders was 7.48 months (<1–23). Treatment was well tolerated. The most common non-hematological toxicities were nausea and fever.Conclusions: AZA appears to be effective and well tolerated in CMML.

Profile of paediatric patients with pulmonary hypertension judged by responsiveness to vasodilators.

To describe the demographic and haemodynamic variables of children presenting with primary pulmonary hypertension or pulmonary hypertension appearing or persisting after surgical correction of congenital heart defects and to assess the acute effect of vasodilator drugs on their pulmonary vascular bed. Retrospective review. Paediatric cardiology department and intensive care unit of a large tertiary centre. Fourteen consecutive patients presenting with primary pulmonary hypertension (group 1) or pulmonary hypertension persisting or appearing late after complete surgical repair (group 2). Baseline haemodynamic measurements were taken in room air at rest and repeated in 100% oxygen. With constant monitoring of heart rate and pulmonary and systemic arterial pressures, patients were given serial intravenous, sublingual, or oral incremental doses of vasodilators (mean 4.1 trials per patient). The maximum effect of the drug was charted. A positive response to acute vasodilator tests was defined as a decrease in mean pulmonary or mean systemic arterial pressure > 15% with the mean pulmonary artery pressure not reaching the systemic level and either no change or an increase in mean systemic arterial pressure. Haemodynamic variables between groups (1 v 2, responders v non-responders, patients experiencing or not experiencing adverse effects to vasodilators) were compared by a two tailed unpaired Student's t test, and their survival curves were compared by the log rank statistic. Groups are small and definitive conclusions are difficult to draw, but the baseline haemodynamic assessments were not significantly different between group 1 and 2 or between responders and non-responders to vasodilators. Patients experiencing adverse effects had a higher pulmonary vascular resistance (p = 0.04) and wedge pressure (p = 0.02) than those without adverse effects. Of the vasodilators used, tolazoline, hydralazine, salbutamol, phentolamine, and phenoxybenzamine were ineffective. A positive response was seen in five of 13 patients given oxygen, in one of eight given prostacyclin, four of 12 given nifedipine, four of eight given diltiazem, one of six given captopril, and two of seven given glyceryl trinitrate. Estimates of survival of the population with primary pulmonary hypertension were 37% at one year and 12% at 2.5 years. Survival was significantly shorter in the non-responders than in the responders (p = 0.005). Children with primary pulmonary hypertension present to the cardiologist at a young age (five of eight were younger than 7 years) but with advanced pulmonary vascular disease and have a poor prognosis. 64% of group 1 and group 2 patients had a positive response to acute treatment with at least one vasodilator. Calcium channel blockers were the most effective agents. There was a positive response to drugs despite a negative response to acute treatment with oxygen. The survival of non-responders was shorter than that of the responders.

Combination of recombinant interferon alpha-2a and vinblastine in advanced renal cell cancer.

Among 40 evaluable patients with metastatic renal cell cancer treated by high-dose interferon alpha-2a in combination with vinblastine, the authors have observed a 42.5% response rate. The 8 months' median duration of remissions is relatively short but some patients experience very long remissions, lasting many months after discontinuation of therapy. The survival of responding patients is significantly longer than the survival of nonresponders. The diverging results of other studies of the same combination are discussed; its efficacy is certainly dependent on the type of interferon, on the dose actually administered, and on the compliance to this often poorly tolerated treatment.

Efficacy of the M-2 protocol in previously untreated patients with advanced multiple myeloma.

37 consecutive, previously untreated patients with advanced multiple myeloma (16 patients Stage II, 21 patients Stage III) were treated with a five drug regimen consisting of carmustine, melphalan, vincristine, cyclophosphamide and prednisolone (M-2-protocol) in a prospective manner. Remission was achieved in 24 patients (65%). The median time to remission was 10 weeks, the median duration of remission 15,3 months. Median survival time from the onset of treatment was 24 months for all patients. Responding patients have a projected 65% three year survival. Median survival in non-responders was 10 months. 8 patients died during the first year of treatment. These results do not confirm the favourable results with this drug combination obtained in a previous trial. The discrepancy may be explained by a higher proportion of poor risk patients in the present study.

Combination Chemotherapy for Terminal-Phase Chronic Granulocytic Leukemia: Cancer and Leukemia Group B Studies

A 34% response was obtained in 202 evaluable patients in the terminal phase of chronic granulocytic leukemia using combinations of hydroxyurea, 6-mercaptopurine, and corticosteroids. Twelve percent of responses were complete and 22% partial. Overall median survival was 12 wk. A 30 wk median survival for responding patients was statistically superior to the 7-wk survival for nonresponders (p less than 0.001). Response was inversely correlated with toxicity. No responses were obtained in patients sustaining both severe infectious and bleeding complications. No benefit could be demonstrated from the addition of vincristine in induction and daunorubicin for consolidation. Although the response frequency and duration of survival with this combination chemotherapy were generally superior to those previously reported by our group, the terminal phase of chronic granulocytic leukemia still remains a formidable and generally refractory disease.

Combination chemotherapy for terminal-phase chronic granulocytic leukemia: cancer and leukemia group B studies

A 34% response was obtained in 202 evaluable patients in the terminal phase of chronic granulocytic leukemia using combinations of hydroxyurea, 6-mercaptopurine, and corticosteroids. Twelve percent of responses were complete and 22% partial. Overall median survival was 12 wk. A 30 wk median survival for responding patients was statistically superior to the 7-wk survival for nonresponders (p less than 0.001). Response was inversely correlated with toxicity. No responses were obtained in patients sustaining both severe infectious and bleeding complications. No benefit could be demonstrated from the addition of vincristine in induction and daunorubicin for consolidation. Although the response frequency and duration of survival with this combination chemotherapy were generally superior to those previously reported by our group, the terminal phase of chronic granulocytic leukemia still remains a formidable and generally refractory disease.