Conventional Chemotherapy Group Research Articles

Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis

Background:This study aims to evaluate the effectiveness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided neoadjuvant chemotherapy for increasing resectability in patients with unresectable colorectal liver metastasis.Patients and methods:Patients were randomised into two groups: Group A was treated by conventional chemotherapy regimen and Group B was treated by chemotherapy regimen according to the ATP-CRA. Three chemotherapeutic agents (5-fluorouracil, oxaliplatin and irinotecan) were tested by ATP-CRA and more sensitive agents were selected. Either FOLFOX or FOLFIRI was administered. Between Group A and B, treatment response and resectability were compared.Results:Between November 2008 and October 2010, a total 63 patients were randomised to Group A (N=32) or Group B (N=31). FOLFOX was more preferred in Group A than in Group B (26 out of 32 (81.3%) vs 20 out of 31 (64.5%)). Group B showed better treatment response than Group A (48.4% vs 21.9%, P=0.027). The resectability of hepatic lesion was higher in Group B (35.5% vs 12.5%, P=0.032). Mean duration from chemotherapy onset to the time of liver resection was 11 cycles (range 4–12) in Group A and 8 cycles (range 8–16) in Group B.Conclusion:This study showed that tailored-chemotherapy based on ATP-CRA could improve the treatment response and resectability in initially unresectable colorectal liver metastasis.

Clinical Observation of Modified FOLFOX Chrono-chemotherapy for Advanced Gastrointestinal Cancer

Objective To invasigate the efficacy and side effects differences between modified FOLFOX chrono-chemotherapy with oxaliplatin(L-OHP) combined with 5-fluorouracil(5-Fu) and folinic acid(LV) and standard FOLFOX4 chemotherapy with L-OHP,5-Fu and LV inadvanced gastrointestinal cancer.Methods One hundred and eighty-three patients with advanced gastrointestinal cancer were randomly divided into two groups:chrono-chemotherapy group and conventional-chemotherapy group.Ninety-two patients in chrono-chemotherapy group was infused L-OHP 85～100 mg/m2 from 14:00 to 18:00(day 1),with the highest plasma drug level at 16:00;LV 200mg/m2 and 5-Fu 1000mg/m2 were administered from 22:00 to 10:00(day 1~2),with the highest plasma drug level at 4:00 in the morning,using a sinusoidal infusion pump.91 cases in conventional-chemotherapy group were given standard FOLFOX4 conventional chemotherapy: L-OHP 85～100mg/m2 was infused for 2 hours(day 1);LV 200mg/m2 for 2 hours(day 1~2);5-FU 400mg/m2 was intravenously injected(day 1~2) and 600mg/m2 infused continuously for 22 hours(day 1~2).L-OHP was administrated at normal working time,followed by LV,and then 5-Fu.Chemotherapy was given repeatedly every 30 days for at least 2 cycles.Result The effective rate in chrono-chemotherapy group was 65.2%,and the KPS score increased by 18.7,which were higher than those of Conventional chemotherapy group(P0.05).The occurrence of adverse effects was obviously lower than that of conventional chemotherapy group(P0.05).Conclusion Compared with the conventional chemotherapy regime,modified FOLFOX chrono-chemotherapy had a higher effective rate,lower occurrence of adverse effects and better tolerability,which deserves the clinical expansion.

Quality of Life of Long Term Survivors with Follicular Lymphoma After High-Dose Chemotherapy with Autologous Stem Cell Transplantation and Conventional Chemotherapy.

AbstractAbstract 3808 Introduction:High-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT) is frequently applied in eligible patients with relapsed or refractory follicular lymphoma (FL). The toxicity of HDCT, however, might manifest itself in the respective patients' reduced quality of life (QoL). In this study we investigated the QoL of long term survivors after HDCT in comparison with patients after conventional chemotherapy and the healthy German population. Patients and Methods:QoL was evaluated with the standardized questionnaires EORTC QLQ-C30 and EQ-5D. A total of 124 patients with FL were included in the study. 63 patients (29 female) with a median age of 60.4 (range 41–80) received HDCT with PBSCT between 1992 and 2002. This group was compared with 61 patients (38 female) with a median age of 62.9, range 31–81) who were treated with Rituxmab and CHOP chemotherapy and supplementary radiation in our institution. 55 patients of 63 (88%) of the HDCT group and 25 of 61 (41%) patients of the conventional group were in continuous complete remission (CR). Median follow-up for the HDCT group is 9 years and for the conventional chemotherapy group it is 4.4 years. In addition, QoL of the patients was compared to QoL of healthy people on the basis of two studies about the general health status of the German population (R. Schwarz and A. Hinz: “Reference data for the quality of life questionnaire EORTC QLQ-C30 in the general German population,” European Journal of Cancer 37 [2001]: 1345–1351; H. H. König et al.: “Health Status of the German Population: Results of a Representative Survey Using the EuroQoL Questionnaire,” Gesundheitswesen 67 [2005]: 173–182). Results:In the HDCT group, the results of the questionnaires show a reduced QoL compared to the healthy population. Regarding the three main categories of the EORTC QLQ-C30, the mean sum score for global health state (ghs) is 71.38, for functional state (fs) 78.38 and for symptomatic state (ss) 18.60 (the ideal score being 100.00 for the first two items and 0.00 for the latter). The mean value for EQ-5D is 0.911 (ideal value: 1.000) and that for VAS is 75.52 (ideal value: 100.00). The one sample t-test evaluation shows that the decrease in QoL is significant with p<0.05 in four of five of the subcategories of the functional state; six of the nine subcategories of the symptomatic state, namely fatigue, dyspnoea, insomnia, constipation, diarrhoea and financial difficulties. Patients who received conventional chemotherapy (ghs: 67.04; fs: 70.49; ss: 25.01) also showed a reduced QoL compared to the healthy population in all of the three main categories of the EORTC-QLQ-C30, in particular in the category of functional and symptomatic state. These differences were statistically significant in all subcategories of the functional state namely physical,-role,-emotional,-cognitive,- and social functioning (p=0.001). The differences of the symptomatic state were statistically significant in seven of nine subcategories, namely fatigue, pain, dyspnoea, insomnia, constipation, diarrhea and financial difficulties. When QoL of the HDCT group and the conventional therapy group were compared, there were significant differences in favor of the HDCT group only in the functional subcategory social functioning (p=0.04) and the symptomatic subcategory pain (p=0.01), with no significant differences in all other categories. In the EQ-5D questionnaire, we found a reduced QoL in patients after conventional chemotherapy compared to HDCT patients (p=0.05) and healthy people (p=0.02). Conclusions:In this long term follow up study, we found a reduced QoL in FL patients after conventional chemotherapy as well as after HDCT compared to the healthy population. There was a tendency of a better QoL in patients of the HDCT group compared to patients of the conventional chemotherapy group, maybe due to a higher proportion of patients in CR or a longer follow up period in the HDCT group. We conclude that the negative impact of both HDCT and conventional therapy on QoL of patients with follicular lymphoma should not be underestimated and should lead to the development of less toxic therapy strategies. Disclosures:No relevant conflicts of interest to declare.

Curative effect of low dose cytarabine and aclarubin in combination with granulocyte colony-stimulating factor priming (CAG regimen) on patients with the intermediate and high-risk myelodysplastic syndrome

To evaluate the curative effect and adverse effect of low dose cytarabine and aclarubin in combination with granulocyte colony-stimulating factor priming (CAG regimen) on patients with the intermediate and high-risk myelodysplastic syndrome. A: total of 46 patients with intermediate and high-risk myelodysplastic syndrome was retrospectively analyzed. Twenty-eight patients received CAG regimen and 18 received conventional chemotherapy. CAG regimen: aclarubicin 10 mg/(m2.d)intravenously daily, Day 1~8; cytarabine 10 mg/ m2 subcutaneously once every 12 hours, Day 1~14; and subcutaneously use of granulocyte colony-stimulating factor 200 mug/(m2.d) until 12 hours before the last use of cytarabine. The initial outcome was evaluated after the first course of treatment. The responders received the second course. The ultimate therapeutic effect was evaluated after the 2 courses. The overall response rate in the CAG regimen group was 78.6% (22/28). Thirteen patients (46.4%) responded, 5 (17.9%) showed partial response, and 4 (14.3%) hematologic improvement. The overall response rate in the conventional chemotherapy group was 50%(9/18). Six patients (33.3%) achieved complete response, 2 (11.1%) partial response, and 1(5.6%) hematologic improvement. The overall response rate of the CAG group was significantly higher than that in the control group (P<0.05). The adverse effects of CAG regimen were bearable. With acceptable adverse effect, CAG regimen is effective for the intermediate and high-risk myelodysplastic syndrome. Long-time outcome needs further observation.

Clinical characteristics and outcomes of adults with Philadelphia chromosome positive and/or bcr-abl positive acute lymphoblastic leukemia: a single center study from China

The study reviewed 389 adult patients with acute lymphoblastic leukemia (ALL) and 110 patients (28.3%) were diagnosed as Philadelphia chromosome positive (Ph-positive) and/or bcr-abl positive ALL. The special group had the same clinical characteristics as other studies, except for relatively young age and high incidence of both P190 and P210 fusion proteins expression. The complete remission (CR) rate in conventional chemotherapy (CT) group and in chemotherapy combined with imatinib (ICT) group was 84.7% and 96.0%, respectively. The 2-year disease-free survival (DFS) and overall survival (OS) were 0 and 23.6 ± 6.9%, respectively in CT group; the 2-year DFS and OS were 22.1 ± 8.8% and 41.6 ± 10.0%, respectively in ICT group; and in allogeneic stem cell transplantation (SCT) group, the 2-year DFS and OS were 48.2 ± 13.9% and 53.1 ± 12.7%, respectively. The results of the study indicated that introducing imatinib into treatment of patients with Ph-positive ALL could improve CR rate and survival, especially as early as possible, and allogenic SCT was still the first choice for these patients if they had suitable donors.

Quality of Life of Long Term Survivors with Hodgkin's Lymphoma After High-Dose Chemotherapy with Autologous Stem Cell Transplantation and Conventional Chemotherapy.

Abstract 2495Poster Board II-472 Introduction:High-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT) is frequently applied in eligible patients with relapsed or refractory Hodgkin's disease. The toxicity of HDCT, however, might manifest itself in the respective patients' reduced quality of life (QoL). In this study we investigated the QoL of long term survivors after HDCT in comparison with patients after conventional chemotherapy and the healthy German population. Patients and Methods:QoL was evaluated with two standardized questionnaires: EORTC QLQ-C30 and EQ-5D. The cancer-specific EORTC-QLQ-C30 consists of thirty questions concerning three main categories: global health state, functional and symptomatic state. The single questions belonging to functional and symptomatic state can furthermore be grouped into different subcategories. The EQ-5D visualizes five dimensions of health: mobility, self-care, daily activities, pain, and anxiety. In addition to that, the visual analogue scale (VAS) is included to outline the patients' overall health state. A total of 98 patients were included in the study. 37 patients (13 female, 24 male) with a median age of 46 (range 23-72) received HDCT with PBSCT between 1986 and 2007. This group was compared with 61 patients (36 female, 25 male; median age 41, range 21-72) treated with conventional chemotherapy and supplementary radiation in our institution. In the conventional chemotherapy group BEACOPP was used in most cases (n=31), followed by ABVD (n=20), a combination of both (n=8) and ABV (n=2). All patients were in continuous clinical remission. Median follow-up for the HDCT group is 11 and for the conventional chemotherapy group 3.5 years. In addition, Qol of the patients was compared to QoL of healthy people on the basis of two studies about the general health status of the German population (R. Schwarz and A. Hinz: “Reference data for the quality of life questionnaire EORTC QLQ-C30 in the general German population,” European Journal of Cancer 37 [2001]: 1345-1351; H. H. König et al.: “Health Status of the German Population: Results of a Representative Survey Using the EuroQoL Questionnaire,” Gesundheitswesen 67 [2005]: 173-182). Results:In the HDCT group, the results of the questionnaires show a reduced QoL compared to the healthy population. Regarding the three main categories of the EORTC QLQ-C30, the mean sum score for global health state (ghs) is 68.69, for functional state (fs) 72.49 and for symptomatic state (ss) 21.55 (the ideal score being 100.00 for the first two items and 0.00 for the latter). The mean value for EQ-5D is 0.880 (ideal value: 1.000) and that for VAS is 71.60 (ideal value: 100.00). The one sample t-test evaluation shows that the decrease in QoL is significant with p<0.05 in all of the subcategories of the functional state; four of the nine subcategories of the symptomatic state, namely fatigue, dyspnoea, diarrhoea and financial difficulties. Compared to the group of patients who received conventional chemotherapy (ghs: 73.92; fs: 77.36; ss: 16.27), there is a tendency towards reduced QoL in patients with HDCT in all of the three main categories of the EORTC-QLQ-C30, in particular in the category of symptomatic state. However, these differences were not statistically significant, with the exception of the subcategory of dyspnoea (p<0.001). In the EQ-5D questionnaire, there was a trend for reduced QoL of patients after HDCT compared to conventional chemotherapy patients and healthy people, however these effects were not significant (p = 0.06 and p = 0.089). Conclusions:In this long term follow up study, QoL is reduced in patients after HDCT as well as in patients after conventional treatment compared to the healthy population. There was a trend that QoL might be worse in the HDCT group compared to the conventional therapy group; however this effect was not statistically significant. We conclude that the negative impact of both HDCT and conventional therapy on the QoL of long term survivors with Hodgkin's lymphoma should not be underestimated and should lead to the development of less toxic therapy strategies. Disclosures:No relevant conflicts of interest to declare.

Double allogeneic hematopoietic SCT as a rescue therapy for poor-risk hematological malignancies

The prognosis of patients with poor-risk or relapsed hematological malignancies is dismal. The dose intensification necessary to achieve subsequent CR is limited by the toxicity of chemotherapy. Treatment intensification with double allogeneic HSCT (dHSCT) may enhance the antileukemic effect and reduces treatment-related toxicity associated with prolonged aplasia during reinduction. We evaluated this approach in 23 patients, nine with primary refractory disease or relapse after conventional chemotherapy (group I) and 14 with relapses after allogeneic HSCT (group II). Double HSCT was feasible in all patients. At the end of the observation period, 6 of 23 (26%) patients were still alive and in remission with a median observation time of 60 months (1-153). The overall survival probability at 1 year was 41% (95% confidence interval (CI), 21-62%), transplant-related mortality (TRM) 28% (9-47%) and the incidence of relapse 42% (18-66%). The TRM in groups I and II were 22 and 36% and the relapse rate 33 and 50%, respectively. In conclusion, we have shown the feasibility of dHSCT with an acceptable TRM, irrespective of a previous allogeneic HSCT. Whether this approach offers a survival benefit for patients with poor-risk leukemias has to be tested in larger prospective trials.

Additional chromosomal abnormalities and their prognostic significance in adult Philadelphia-positive acute lymphoblastic leukemia: with or without imatinib in chemotherapy

The study analyzed the characteristics and prognostic significance of additional chromosomal abnormalities in 110 Chinese adults with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL). Secondary aberrations were present in 60.9% of the cases. All chromosomes were involved in secondary aberrations, and chromosomes 9, 7, 21, 18, and 14 were most frequently abnormal. Fifty of 110 patients (45.5%) had at least one normal metaphase cell in their chromosome preparations at diagnosis. Patients with additional aberrations had shorter disease-free survival (DFS) and overall survival (OS) in chemotherapy combined with imatinib (ICT) group and only shorter DFS in conventional chemotherapy (CT) group. The existence of normal metaphase cells was associated with a superior survival in CT group, but not in ICT group. Patients with loss of chromosomes 7, 7p, 9, and 9p had inferior outcome compared to patients with other secondary aberrations and those without secondary aberrations, in both CT and ICT group.

High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years

AbstractAutologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. The multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide. The 9-year overall survival (OS) was similar in the HDT and conventional chemotherapy groups (76% and 80%, respectively). The 9-year progression-free survival (PFS) was higher in the ASCT than the chemotherapy group (64% vs 39%; P = .004). A PFS plateau was observed in the HDT group after 7 years. On multivariate analysis, OS and PFS were independently affected by the per-formance status score, the number of nodal areas involved, and the treatment group. Secondary malignancies were more frequent in the HDT than in the chemotherapy group (6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs 1 acute myeloid leukemia, P = .01). The occurrence of a PFS plateau suggests that a subgroup of patients might have their FL cured by ASCT. However, the increased rate of secondary malignancies may discourage the use of purged ASCT in combination with TBI as first-line treatment for FL. This trial has been registered with ClinicalTrials.gov under identifier NCT00696735.

Allogeneic Stem Cell Transplantation (Allo-SCT) in Adults with Acute Myelogenous Leukemia (AML). Final Analysis of JALSG AML97 Study

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is considered to be the most intensive post remission treatment consisting of high-dose chemoradiotherapy and allo-immune mechanisms. However, the powerful anti-leukemic effects of this treatment are counterbalanced by a high incidence of treatment-related mortality (TRM), thus allo- SCT has not always been considered superior to chemotherapy. The aim of this study was to investigate the efficacy of allo-SCT as a postremission treatment in patients with intermediate/poor risk AML in first CR. Previously untreated patients aged 15 – 50 years were eligible. Patients received standard induction therapy consisting of cytarabine (100 mg/ m2 d1–7) and idarubicin (12 mg/m2 d1- 3). If the patients did not achieve remission after the first induction therapy, then the same induction therapy was given again. The patients who achieved CR were randomized into an intensified short-course postremission chemotherapy group (arm A) or conventional JALSG postremission chemotherapy group (arm B). Patients were also categorized into good, intermediate or poor risk groups by risk factors selected from previous JALSG AML trials using univariate and multivariate analyses. Intermediate or poor risk patients with living siblings were tissue typed. If an HLA matched sibling was found it was assumed that the patient would receive allo-SCT during CR1 (donor group). Those without living or HLA matched siblings were assigned to the no-donor group that continued receiving chemotherapy. The disease-free survival (DFS) rates, the relapse incidence rates (RI), TRM and the overall survival (OS) rates of the patients of the donor group were compared with those of the no-donor group on the basis of the intention to treat.Result: Of 503 patients aged 15 – 50 years old registered between December 1997 and July 2001, 397 achieved complete remission (CR). The 5-year OS rate of the CR patients with good, intermediate and poor risk was 68%, 43% and 29%, respectively (p<0.001), showing successful stratification by the JALSG scoring system. Among those who achieved CR with intermediate or poor risk, 75 with and 95 without an HLA matched sibling were assigned to the donor and no-donor groups, respectively. The actual risk of relapse at 8 years was significantly lower in the donor group than in the no-donor group (54% versus 78%, p=0.009). The TRM did not significantly differ between the donor group and the no-donor group (16% versus 17%, p= 0.948). The lower relapse rate in the donor group resulted in a significantly better DFS compared with the no-donor group (38% versus 18%, p=0.017). The significant superiority of DFS in the donor group was translated into a higher OS rate, however, the difference in OS between the two groups did not reach statistical significance (45% versus 28%, p=0.089). The OS of the patients younger than 35 years of age were comparable between the donor group and the no-donor group. However, the OS in the donor group patients older than 36 years old was significantly better than the other (47% versus 23%, p= 0.032).Conclusions: Our study showed that allo-SCT reduced the risk of relapse and contributed to the survival advantage of AML patients aged from 36 to 50 years old with intermediate or poor risk.

Impact of different post-remission strategies on quality of life in patients with acute myeloid leukemia

The impact on quality of life of allogeneic stem cell transplantation or conventional chemotherapy in patients with acute myeloid leukemia remains unclear, mainly because of a lack of studies with long-term follow-up. The German AML-Intergroup, therefore, initiated a survey on quality of life of patients with a relapse-free survival of at least 5 years after first-line treatment. The EORTC Quality of Life Core Questionnaire (QLQ-C30), supplemented by information on self-assessed concomitant diseases, late treatment effects, and demographics was used. The questionnaire was returned by 419 of 818 patients (51.2%) identified by six study groups. The patients' median age at diagnosis was 42 years, and the median follow-up period was 8 years. One hundred and seventy patients were treated with stem cell transplantation (121 allogenic, 49 autologous) in first complete remission; the other 249 patients were treated with conventional chemotherapy. The ECOG activity index revealed normal activity in 45% vs. 60% of the patients in the allogeneic stem cell transplantation vs. conventional chemotherapy groups, respectively and disabled person status in 60% vs. 35%. All QLQ-C30 functions, except physical functioning and pain, were poorer in allogeneic stem cell transplantation patients. Problems in leisure-time activities, social life, and financial management, sexual limitations and adverse effects were significantly more frequent in patients after allogeneic stem cell transplantation than after conventional chemotherapy. Multivariate logistic regression models on global health status revealed concomitant disease, age > 45 years, and allogeneic stem cell transplantation as significant risk factors. These results indicate that, compared to conventional chemotherapy, allogeneic stem cell transplantation has a significantly worse long-term impact on quality of life. This needs to be considered when treatment options are discussed.

Does consolidation with autologous stem cell transplantation improve the outcome of children with metastatic or relapsed Ewing sarcoma?

To evaluate the role of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) as consolidation therapy for children with high-risk Ewing sarcoma (ES) treated at The Hospital for Sick Children (SickKids), Toronto. The charts of children treated for high-risk ES (defined as metastatic at diagnosis or relapsed) between 1990 and 2005 at SickKids were reviewed. Forty-five children were identified. Twenty patients received ASCT after induction with vincristine, doxorubicin, ifosfamide, cyclophosphamide, and etoposide. Patients with resectable tumor or lung metastases underwent surgery and those with non-resectable tumors were treated with irradiation. Twenty-five patients were treated with conventional chemotherapy (CC). Primary metastatic patients were treated with either a local protocol or as per POG 9354. At relapse, patients were treated with topotecan, cyclophosphamide, then ifosfamide, carboplatin, and etoposide (ICE). Local control was attained with surgery and/or irradiation. Ten of the 20 patients treated with ASCT are alive (median follow-up 6 years), with 8/10 being in remission more than 5 years from diagnosis. The 3-year overall survival (OS) for ASCT was 59%, (95% CI: 36%, 81%) compared to 34% (14%, 53%) for patients treated with CC (P-value = 0.06). The 3-year event-free survival (EFS) for the ASCT was 39% (17%, 60%) compared to 32% (13%, 50%) in the CC group (P = 0.08). ASCT appears to add some benefit to conventional multimodality therapy for children with high-risk ES. Randomized controlled trials are warranted.

Natural History of Southeast Asian Chronic Myeloid Leukemia Patients with Different BCR-ABL Gene Variants

Little evidence exists regarding the prognostic impact of the major BCR-ABL gene variants (e13a2 and e14a2) in chronic myeloid leukemia (CML) patients diagnosed and treated in the developing Asian countries. In this study, 139 Thai CML patients were followed for a median period of 3 years (range 18–43 months). Clinical presentations of both BCR-ABL gene variant groups (73% e14a2+ and 27% e13a2+) were similar, although e14a2+ patients tended to be older (42 vs. 37 years) and had higher white blood cell counts than e13a2+ patients. The majority of patients in both groups presented with Sokal stage 2–3 (score >0.8) and were categorized as Hasford’s intermediate- to high-risk groups (score >780). All patients received oral chemotherapy and 13% underwent allogeneic stem cell transplantation. None received oral tyrosine kinase inhibitors. In the conventional chemotherapy group, the overall survival (OS) rate was slightly better in e14a2+ than in e13a2+ patients (p = n.s.). The median survival in e14a2+ and e13a2+ patients who did not receive stem cell transplantation was 49 and 33 months, respectively (p = n.s.). The type of blastic crisis in e14a2+ and e13a2+ patients was similar, being predominantly myeloid. In conclusion, CML patients in Thailand, despite being much younger, had a comparable OS with those in the Western countries, with no different OS between e14a2+ and e13a2+ patients. Future studies should focus on the impact of novel oral BCR-ABL tyrosine kinase inhibitors on the outcome of Thai CML patients with different BCR-ABL gene variants.

The factors affecting objective response in patients with advanced malignant tumor treated with H101, an E1B-55kD deleted oncolytic adenovirus

13166 Background: H101 is E1B-55kD deleted oncolytic adenovirus which can selectively replicate in tumor cells. Previous phase I/II clinical trials have shown that H101 has certain anti-tumor effects and is safe when applied to patients by intratumoral injection. The aim of this study is to identify the factors affecting tumor response in patients with advanced malignant tumor treated with H101. Methods: All patients in H101 phase II clinical trial were retrospectively reviewed. They were treated with either H101 alone (group A) or H101 combined with conventional chemotherapy (group B). H101 was administrated by intratumoral injection at the dosage of 5×1011 viral particles, once a day for 5 consecutive days. The objective response was evaluated according to WHO criteria and the adverse events were recorded. All information required for this study was retrieved from the database of H101 phase II clinical trial. Chi square test and stepwise multivariable regression were used for statistic analysis with a significant level of p&lt;0.05. Results: There were 106 evaluable patients in this study, 54 in group A (36 males and 18 females, age: 36–78 years), 52 in group B (35 males and 17 females, age: 18–76 years). The diagnoses of these patients include head &amp; neck cancer (54), breast cancer (13) and others (39). All were in the advanced stage of the disease, and refractory or resistant to chemo and radio therapy. The objective response rate was higher in group B (23.1%) as compared to group A (16.7%). In patients with response (CR or PR), 62.5% of them experienced fever after the injection of H101, in contrast, only 18.9% of the patients without response did so. The difference was statistically significant (p&lt;0.01). In the stepwise multivariable regression analysis, tumor response was used as dependent variable, and the independent variables included demographic data, clinical and pathologic type of the tumor, and treatment regimen. The result revealed that tumor response was positively correlated with the fever after H101 injection (p&lt;0.01). Conclusions: H101 has certain anti-tumor efficacy in patients with advanced malignancies, which might be enhanced by the fever after H101 injection and/or combining with chemotherapy. [Table: see text]

Allogeneic Transplantation from an HLA-Matched Family Donor in First Complete Remission of Acute Myeloid Leukemia Had an Adverse Impact on Quality of Life in Patients Followed for at Least Five Years after Treatment: A Survey of the German AML Intergroup on 525 Patients.

The impact of allogeneic blood stem cell transplantation (Allo-SCT) in comparison to conventional chemotherapy (CCT) in AML on quality of life remains unclear mainly due to a lack of studies with long term follow-up. Therefore the German AML-Intergroup initiated a survey on quality of life for patients treated within 1 of 8 German prospective multicenter treatment trials. All patients completed a self-report questionnaire either when they returned for follow-up outpatient visits or by mail. Patients completed the EORTC Quality of Life-Core Questionnaire (QLQ-C30) supplemented by self-assessed concomitant diseases, late treatment effects and demographic details including percentage of disability. 525 patients (median age: 46 years at diagnosis; median follow up period: 9 years) returned their questionnaires, 244 after SCT in 1. CR (189 allo; 55 auto) and 281 after CCT. Recovery-rate of the questionnaires was 55% ranging from 40% to 79% in the different trial cohorts. Due to low numbers after auto-SCT these patients were excluded from further analysis. The ECOG activity index revealed normal activity in 40% and 58% and disabled person card in 63% and 37% of the patients in the allo-SCT and CCT groups, respectively. Impaired vision, cataract surgery, chronic skin disorders and treatment of hormonal disorders were reported significantly more often in allo-SCT-patients, whereas osteoarthritis, cardiac insufficiency and unspecific back pain were slightly more frequent in CCT patients, mainly due to a higher median age in the CCT-group. All QLQC-30 functions except physical functioning and pain were in favor of CCT (p<0.001 in each variable). Problems in leisure-time activity, evenness and social life (friends and family) as well as financial management were significantly more frequent in patients after Allo-SCT than in patients after CCT, whereas the general assessment of positive attitude in life showed no difference between the two groups (62% CCT and 64% Allo-SCT). Multivariate logistic regression models on global health status and fatigue were performed. Actually concomitant disease (odds ratio 6.68 95%-CI 3.83–11.66), age > 45 years (odds-ratio 2.57 95%-CI 1.47–4.50) and Allo-SCT (odds ratio 2.10 95%-CI 1.20 – 3.69) showed significant adverse effect on global health status. Similarly unfavorable effects were evaluated for actually concomitant disease and Allo-SCT on fatigue. These results indicate that Allo-SCT compared to intensive chemotherapy had a significant negative impact on quality of life and this needs to be considered when reviewing treatment options.

The Survival of Multiple Myeloma Patients: A Single Institution Study.

Background: For a long time, multiple myeloma has been a disease with a poor outcome. High dose (melphalan) chemotherapy followed by autologous stem cell transplantation has been reported to improve the overall and progression-free survival of these patients.Objective: To determine the survival of multiple myeloma patients treated with conventional chemotherapy and compare it with that of patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation.Design/Methods: 83 myeloma patients treated at a single institution were included in this retrospective study. They were divided into two groups: one group of patients who were received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (n=42) and one group of patients who only received conventional chemotherapy and were eventually also treated with thalidomide and/or corticosteroids (n=41). The distribution of the stages of the disease according to Salmon and Durie were similar in both groups of patients. For both groups, the overall and progression-free survival was calculated.Results: In the general analysis, myeloma patients who underwent an autologous transplant had a significantly longer overall survival (58.8 vs. 52.2 months, p=0.036) and progression-free survival (39.6 vs. 11.8 months, p < 0.001) in comparison with the conventional chemotherapy group. If analysis was restricted to those patients who were transplanted as a first-line treatment, there was no significant difference in overall survival in comparison with conventional chemotherapy (51.8 vs. 52.2 months, p= 0.422); progression-free survival was significantly better in the first-line transplant arm as compared to the conventional chemotherapy arm (35.4 vs. 11.8 months, p= 0.003). As the median age in the transplant arm was significantly lower than in the conventional chemotherapy arm, we also performed a sub-analysis of patients who were between 60 and 70 years of age at diagnosis; there was no significant difference in overall survival between the two groups (60.7 vs. 69.5 months, p= 0.656), while the progression-free survival was again better in the autologous transplant group as compared to the conventional chemotherapy group (41.0 vs. 8.4 months, p= 0.020).Conclusion: High-dose chemotherapy and autologous stem cell transplantation in the treatment of myeloma is associated with improved progression-free survival and in the general analysis, with improved overall survival. The overall survival of patients who were only treated with conventional chemotherapy is somewhat higher (more than 4 years) as compared to that of historical controls (2–3 years).

High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors: a mechanism for post-bone marrow transplantation osteopenia.

Osteoporosis is a sequela of hemopoietic cell transplantation with a complex multifactorial pathogenesis in which the relative role of chemotherapy and irradiation is not completely understood. Therefore, the authors investigated the toxicity of chemotherapy-only conditioning regimens on bone homeostasis and bone marrow osteoprogenitors, its dose dependency, and the mechanism of chemotherapy-induced osteopenia. Fifty-one patients with high-grade non-Hodgkin lymphoma or breast carcinoma who had been treated previously with high-dose + peripheral blood progenitor cell or conventional chemotherapy or who had not received any treatment (prechemotherapy) were enrolled. The authors measured the bone marrow colony-forming unit fibroblast (CFU-f) and long-term culture-initiating cell frequency, forearm bone mineral density, serum osteotropic hormones and metabolic markers of bone formation (plasma osteocalcin), and resorption (urinary collagen I C-crosslinks). Both high-dose chemotherapy regimens caused a 50% reduction in CFU-f frequency, independently of gonadal function status, whereas conventional chemotherapy and prechemotherapy groups were unaffected. Bone mineral density was measured in 26 non-Hodgkin lymphoma patients and again only high-dose chemotherapy caused a 10% loss in cortical bone and 20% in trabecular bone. No endocrine abnormality was found except for the secondary amenorrhea uniformly induced in the high-dose chemotherapy group. In these patients, plasma osteocalcin unexpectedly failed to increase in response to the menopausal increase in bone resorption rate, showing a selective impairment of the osteoblast compartment to cope with increased functional demand. Chemotherapy without irradiation shows a dose-dependent toxicity to bone marrow stromal osteoprogenitors and can cause osteopenia by direct damage of the osteoblastic compartment, as a mechanism distinct from and summable to hypogonadism.

Autologous bone marrow transplantation for treatment of isolated central nervous system relapse of childhood acute lymphoblastic leukemia. AIEOP/FONOP-TMO group. Associzione Italiana Emato-Oncologia Pediatrica.

The purpose of this study was to assess the role of ABMT in children with ALL who are in 2nd CR after an early isolated CNS relapse. All children experiencing an isolated CNS relapse at 10 AIEOP centers (Associazione Italiana Emato-Oncologia Pediatrica) from 1986 to 1992 were eligible for this study. The series included 69 patients who relapsed within 3 years from diagnosis: 19 underwent ABMT, nine patients underwent ALLO-BMT from an HLA-identical sibling, and 41 received conventional chemotherapy (CHEMO). Statistical analysis was performed using a Cox's regression model, adjusting for the waiting time before transplantation and prognostic factors. The 5 years DFS was 56.3% (s.e. 12.3) for patients in the ABMT group. This compared favorably with the poor result (12.6% (s.e. 5.9)) seen in the CHEMO group. The risk of failures was reduced by one-third in the ABMT group as compared to the CHEMO group in the multivariate analysis (P < 0.01). In the ALLO group four out of nine patients were in CCR 4-5 years post-transplant. This study suggests that ABMT may also represent a valuable therapeutic choice for patients lacking a matched familiar donor in 2nd CR after an early isolated CNS relapse.

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in breast cancer.

Since 1981 we have conducted four studies of the treatment of metastatic and postoperative high-risk breast cancer with high-dose chemotherapy supported by autologous hematopoietic stem-cell transplantation (AHSCT). Study I, involving 56 metastatic cancer patients, proved that induction chemotherapy produces a lasting complete response (CR) in only a few cases despite the achievement of a CR rate higher than that expected from standard chemotherapy. Study II was designed to examine consolidation chemotherapy in metastatic cancer patients responding to induction chemotherapy. At a median follow-up of 26 months (range 2-66), consolidation therapy produced a 5-year progression-free survival rate of 27.1% in 30 patients showing a CR or a partial response to induction therapy and 58.6% in 13 patients showing a CR to consolidation therapy. No treatment-related death occurred during study II. The same regimen used in study I was employed for 58 postoperative high-risk patients in study III. The 10-year disease-free survival rate recorded for patients with > or = 10 positive axillary lymph nodes was significantly higher (P < 0.05) in the AHSCT-supported chemotherapy group than in the conventional chemotherapy group. A double high-dose regimen was adopted for 21 postoperative high-risk patients in study IV. The 3-year disease-free survival rate recorded for 9 patients with > or = 10 positive axillary lymph nodes was 71.4% at a median follow-up of 25 (range 8-45) months. No treatment-related death occurred during study IV. Peripheral blood stem-cell transplantation shortened the duration of bone marrow suppression more effectively than did bone marrow transplantation, thereby optimizing high-dose chemotherapy.

A clinical study of the hematopoietic stem cell transplantation in 112 patients with leukemia and other malignant diseases

One hundred and twelve patients received hematopoietic stem cell transplantation (HSCT), including 91 patients with acute leukemia, 12 patients with chronic myeloid leukemia, 7 patients with lymphoma and 2 patients with myeloma and neuroblastoma respectively. Among them, 14 patients were treated with unpurged autologous bone marrow transplantation (ABMT), 25 patients with purged autologous bone marrow transplantation (PABMT), 40 patients with autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT), 24 patients with allogeneic bone marrow transplantation (Allo-BMT), 9 patients with fetal liver hematopoietic stem cell transplantation (FLHSCT). The three year disease free survival (DFS) rates in these five groups were 683%, 67.5%, 69.54%, 57.12% and 3333% respectively. The relapse rates were 30.76%, 26.80%, 20.8%, 13% and 62.5% respectively. In contrast, in the conventional chemotherapy group, the three year DFS rate and relapse rate were 738% and 76.4% respectively. These results indicated that the APBHSCT group had a quicker hematopoietic reconstitution with less complication of infection. All of these five transplantation groups had much higher three years disease free survival rates than that of the conventional chemotherapy group.