Courses Of Induction Chemotherapy Research Articles

Incidence of bacterial and fungal infections in newly diagnosed acute myeloid leukaemia patients younger than 65 yr treated with induction regimens including fludarabine: retrospective analysis of 224 cases

Infections are the major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). They primarily occur during the first course of induction chemotherapy and may increase the risk of leukaemia relapse, due to a significant delay in consolidation therapy. The intensification of induction chemotherapy and the use of non-conventional drugs such as fludarabine are considered responsible for the increased risk of infections. In this study, we retrospectively analysed the infections occurred in 224 newly diagnosed AML patients </=65 yr, consecutively treated between 1997 and 2002 with an induction regimen including fludarabine, arabinosyl cytosine and idarubicin, with or without etoposide (FLAI/FLAIE), in the context of three multicentric prospective trials (AML97, AML99, AML02). During the induction phase, 146 (65%) patients experienced fever of undetermined origin (FUO), 30 (13%) and 47 (21%) patients had Gram-negative and positive bacteremias, respectively, and 10 (4%) patients developed a probable/proven invasive fungal infection (IFI). The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 10%, 8% and 60% respectively. During consolidation, 75 (35%) patients had FUO, 43 (20%) and 40 (19%) patients had Gram-negative and positive bacteremias, respectively, and 5 (2%) patients developed a probable/proven IFI. The fatality rate for Gram-negative, Gram-positive bacteremias and probable/proven IFI was 14%, 5% and 80% respectively. Interestingly, the overall incidence of microbiologically documented infections during induction was 38% and the incidence of probable/proven IFIs during the induction/consolidation programme was 7%. No infections caused by viruses or opportunistic pathogens were observed neither during induction, nor during consolidation. These data, although retrospectively collected, suggest that fludarabine-based chemotherapy is not associated with an increased incidence of infections, in particular IFIs, compared to conventional regimens commonly used for AML induction.

Preoperative staging of mesothelioma by 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography fused imaging and mediastinoscopy compared to pathological findings after extrapleural pneumonectomy

Extrapleural pneumonectomy (EPP) in MPM may be confined with both morbidity and mortality and careful preoperative staging identifying resectable patients is important. Staging is difficult and the accuracy of preoperative CT scan, 18F-FDG PET/CT scan (PET/CT), and mediastinoscopy is unclear. The objectives were to compare these staging techniques to each other and to surgical-pathological findings. Patients had epithelial subtype MPM, age <or=70 years, and lung function test allowing pneumonectomy. Preoperative staging after 3-6 courses of induction chemotherapy included conventional CT scan, PET/CT, and mediastinoscopy. Surgical-pathological findings were compared to preoperative findings. Forty-two consecutive patients were without T4 or M on CT scan. PET/CT showed inoperability in 12 patients (29%) due to T4 (7 patients) and M1 (7 patients). Among 30 patients with subsequent mediastinoscopy, including 10 with N2/N3 on PET/CT, N2 were histologically verified in 6 (20%). Among 24 resected patients, T4 occurred in 2 patients (8%), and N2 in 4 (17%), all being PET/CT negative. PET/CT accuracy of T4 and N2/N3 compared to combined histological results of mediastinoscopy and EPP showed sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios of 78% and 50%, 100% and 75%, 100% and 50%, 94% and 75%, not applicable and 5.0, and 0.22 and 0.67, respectively. Non-curative surgery is avoided in 29% out of 42 MPM patients by preoperative PET/CT and in further 14% by mediastinoscopy. Even though both procedures are valuable, there are false negative findings with both, urging for even more accurate staging procedures.

A single dose of pegfilgrastim compared with daily filgrastim for supporting neutrophil recovery in patients treated for low-to-intermediate risk acute myeloid leukemia: results from a randomized, double-blind, phase 2 trial

BackgroundPatients with acute myeloid leukemia (AML) are often neutropenic as a result of their disease. Furthermore, these patients typically experience profound neutropenia following induction and/or consolidation chemotherapy and this may result in serious, potentially life-threatening, infection. This randomized, double-blind, phase 2 clinical trial compared the efficacy and tolerability of pegfilgrastim with filgrastim for assisting neutrophil recovery following induction and consolidation chemotherapy for de novo AML in patients with low-to-intermediate risk cytogenetics.MethodsPatients (n = 84) received one or two courses of standard induction chemotherapy (idarubicin + cytarabine), followed by one course of consolidation therapy (high-dose cytarabine) if complete remission was achieved. They were randomized to receive either single-dose pegfilgrastim 6 mg or daily filgrastim 5 μg/kg, beginning 24 hours after induction and consolidation chemotherapy.ResultsThe median time to recovery from severe neutropenia was 22.0 days for both pegfilgrastim (n = 42) and filgrastim (n = 41) groups during Induction 1 (difference 0.0 days; 95% CI: -1.9 to 1.9). During Consolidation, recovery occurred after a median of 17.0 days for pegfilgrastim versus 16.5 days for filgrastim (difference 0.5 days; 95% CI: -1.1 to 2.1). Therapeutic pegfilgrastim serum concentrations were maintained throughout neutropenia. Pegfilgrastim was well tolerated, with an adverse event profile similar to that of filgrastim.ConclusionThese data suggest no clinically meaningful difference between a single dose of pegfilgrastim and multiple daily doses of filgrastim for shortening the duration of severe neutropenia following chemotherapy in de novo AML patients with low-to-intermediate risk cytogenetics.Trial registrationClinicaltrials.gov NCT00114764

Induction chemotherapy followed by concurrent chemoradiation for patients with non-operable stage III non-small-cell lung cancer

Combined modality treatment with chemotherapy (CT) and radiotherapy (RT) in stage III non-small-cell lung cancer is considered as standard therapy. As concomitant CT appears to be beneficial, the choice of anticancer agents and the role of induction chemotherapy is still unresolved. We present our experience based on an induction CT scheme with carboplatin plus paclitaxel followed by RT and concomitant CT. 31 patients with non-operable stage IIIA or IIIB NSCLC without pleural effusion were included in this study: 30 males, 1 female; median age 66 years (range: 50-81); 32% with non-operable stage IIIA and 68% with stage IIIB without pleural effusion; 61% squamous cell carcinoma, 32% adenocarcinoma and 7% other histologies. Regarding performance status (PS), 9.7% PS 0 and 90% PS 1 were included. Patients received 3 courses of induction CT with carboplatin AUC=6 and paclitaxel 175 mg/m(2), administrated i.v. on day 1 of each 21-day cycle, followed by thoracic irradiation (total dose 60-65 Gy, daily fractions 1.8-2 Gy) with two concurrent courses of carboplatin/paclitaxel. 16.2% of the patients achieved complete response, 48.4% partial response, 25.8% stable disease and 9.6% progression of disease. Median progression-free and overall survival was 12 and 18 months, respectively. The most frequent haematological toxicities were grade (G) 3 anaemia in 19.3%, G3 neutropenia in 9.6% and G4 neutropenia in 12.9%. Esophageal G2 toxicity (RTOG) was observed in 28.1% of cases. The induction CT followed by concomitant chemoradiation used in this study appears feasible, safe and effective when administered to an unselected inoperable NSCLC stage III patient cohort in the everyday routine clinical practice. Further, our results are comparable to previously published phase III studies.

Redefining the Role of Induction Chemotherapy in Head and Neck Cancer

Redefining the Role of Induction Chemotherapy in Head and Neck Cancer

The prognostic impact of functional imaging with 123I-mIBG in patients with stage 4 neuroblastoma >1 year of age on a high-risk treatment protocol: Results of the German Neuroblastoma Trial NB97

Aim/Purpose 123I-meta-iodobenzylguanidine ( 123I-mIBG) scintigraphy is well established for staging and evaluation of response in children with high-risk neuroblastoma but its prognostic value in highly intensive first-line treatment protocols is uncertain. The presence of any 123I-mIBG positive tumour tissue was correlated with event-free survival (EFS) and overall survival (OS). Patients and methods The prognostic impact of residual 123I-mIBG uptake into the primary tumour and metastases for predicting outcome in 113 stage 4 neuroblastoma patients >1 year of the German Neuroblastoma Trial NB97 was assessed using a univariate log-rank test and multivariate Cox regression analysis. Results All patients had 123I-mIBG positive disease at initial staging. After four courses of induction chemotherapy, 71% of patients were still 123I-mIBG positive for the primary tumour and 61% for metastases. After six courses, 39% of patients had 123I-mIBG uptake by the primary tumour and 45% residual 123I-mIBG positive metastatic disease. The 123I-mIBG status of the primary tumour site had no bearing on outcome. Residual 123I-mIBG positive metastatic disease after four (3-y-EFS 25.7 ± 5.3% versus 55.9 ± 7.6%, p = 0.009; 3-y-OS 49.8 ± 6.1% versus 65.0 ± 7.3%; p = 0.021) and after six chemotherapy cycles (3-y-EFS 27.5 ± 6.2% versus 47.4 ± 6.4%, p = 0.011; 3-y-OS 50.5 ± 7.1% vs 60.0 ± 6.4%, p = 0.031) was associated with poor outcome. Conclusion Functional imaging with 123I-mIBG scintigraphy can identify poor responders with any persistent metastatic 123I-mIBG uptake who are at a high risk of disease relapse. 123I-mIBG response of the primary tumour site had no bearing on outcome.

Mucormycotic pseudoaneurysm of the common carotid artery with tracheal involvement

Mucormycosis is an emerging and fatal fungal infection. A high index of suspicion and the knowledge of its potential manifestations are essential for early diagnosis. We describe a patient with acute lymphoblastic leukaemia (L2 subtype) who developed a neck mass following a course of induction chemotherapy. Doppler ultrasonography and angiography of the neck revealed a pseudoaneurysm of the right common carotid artery. The patient then developed haemoptysis. Surgical exploration revealed a necrotic right common carotid artery with anteromedial pseudoaneurysm and adjacent tracheal wall perforation. Local debridement and tracheal repair were performed. Nonseptate hypheal invasion (mucormycosis) was found on the microscopic examination of the excised arterial wall. A subsequent recurrence of pseudoaneurysm was treated with local surgical debridement and intravenous amphotericin B (Fungizone) administration. Although rare, clinicians should be aware of these possible presenting features of mucormycosis as early diagnosis and treatment may potentially improve the survival.

Infectious complications after chemotherapy and stem cell transplantation in multiple myeloma: Implications of Fc gamma receptor and myeloperoxidase promoter polymorphisms

Multiple myeloma is associated with a high risk of infections. We hypothesized that Fc gamma receptor (FCGR) and myeloperoxidase (MPO) promoter gene polymorphisms influence the risk of infections after induction chemotherapy (IC) and autologous stem cell transplantation (ASCT). Retrospectively, we analysed 136 patient courses of IC and 113 procedures of ASCT. Genetic analyses were made with PCR techniques on genomic DNA. The incidence rate ratio of sepsis during ASCT in patients homozygous for the G-129MPO promoter type was 0.30 (95% CI: 0.09–0.96). The G-463AMPO promoter polymorphism was not associated with the risk of infections. The polymorphisms of FCGR2A, FCGR3A and FCGR3B were not convincingly associated with infections. The NA1 variant of FCGR3B was strongly skewed with other risk factors, and the results in IC and ASCT were conflicting. Further studies of the G-129AMPO promoter as a potential risk modifier for infections are relevant.

Outcome of adult T-lymphoblastic lymphoma after acute lymphoblastic leukemia-type treatment: a GOELAMS trial

T-lymphoblastic lymphoma is an infrequent disease usually treated as T-acute lymphoblastic leukemia with an induction chemotherapy course and sequential reinduction and maintenance chemotherapy. The T-LBL/ALL-GOELAL02 study evaluated the impact of randomized reinduction chemotherapy against intensified conditioning followed by autologous stem cell transplantation (ASCT), after an induction regimen of the type used for acute lymphoblastic leukemia (ALL). Patients with favorable characteristics were randomized to receive chemotherapy or ASCT. Patients with unfavorable characteristics (bone marrow involvement and age over 35 years old or leukocytosis >30 x 10(9)/L or failure to achieve medullar complete remission [CR] after one induction course) received a second induction course and ASCT. Among 45 patients, the CR rate was 71% after induction and 87% after a second induction course. Within the group of 27 patients with favorable characteristics, ten received ASCT and 17 chemotherapy. Ten patients in the group with unfavorable characteristics received ASCT. The 7-year overall survival and progression-free survival rates were 64 and 65%, respectively. Surprisingly, CR obtained after only two induction courses was associated with improved overall survival (p=0.04). None of the known prognostic factors significantly affected survival. Randomized maintenance or high-dose therapy (HDT) and ASCT or intensified HDT according to initial presentation gave similar overall and relapse-free survival rates. However, HDT allowed sparing of mediastinal irradiation and shortened treatment duration.

Randomized phase II study of cisplatin and 5-FU continuous infusion (PF) versus cisplatin, UFT and vinorelbine (UFTVP) as induction chemotherapy in locally advanced squamous cell head and neck cancer (LA-SCHNC)

We conducted a multicentric randomized phase II trial comparing 5-FU continuous infusion (PF) and cisplatin, UFT and vinorelbine (UFTVP) as induction chemotherapy (IC) in locally advanced squamous cell head and neck cancer (LA-SCHNC). Primary objective was complete response (CR) to IC and overall survival (OS) was a secondary objective. PF: cisplatin 100 mg/m(2) i.v. Day 1 (D1) and 5-FU 1,000 mg/m(2) per day i.v. continous infusion D1-D5, every 21 days. UFTVP: cisplatin 100 mg/m(2) i.v. D1; UFT 200 mg/m(2) per day p.o. D1-D21 and vinorelbine 25 mg/m(2) i.v. D1 and D8, every 21 days. Four IC courses were planned in both arms. A total of 206 patients (pts) were included (PF/UFTVP: 99/107): oral cavity: 8%/10%, oropharynx: 20%/25%, hypopharynx: 17%/14%, larynx: 54%/50%. Stage (TNM, 2002): III: 41%/35%, IVA: 23%/27%, IVB: 35%/38%. Complete response to IC: PF:36%/UFTVP:31% (P: no significative (NS)). G 3-4 toxicity (PF/UFTVP): neutropenia: 52%/72%; febrile neutropenia: 3%/20% (P < 0.001); anaemia:1%/14% (P < 0.001); trombocytopenia: 5%/0% (P = 0.02); mucositis: 15%/7% (P < 0.001). Deaths during IC: 2(2%)/3(3%). IC with UFTVP was associated with a favourable OS in the Cox analysis (actuarial 5 year OS: 49% vs. 34%; HR: 0.67, 95% CI: 0.47-0.95, P: 0.03). Although clinical response is equal in both arms, overall survival (Cox) is better in the UFTVP arm. Febrile neutropenia and anaemia were more frequent with UFTVP while mucositis and trombocytopenia were more severe with PF.

The prognostic significance of leukemic cells clearance kinetics evaluation during the initial course of induction therapy with HAD (homoharringtonine, cytosine arabinoside, daunorubicin) in patients with de novo acute myeloid leukemia

The impact of the percentage of residual leukemic cells (RLCs) at the end of first course of induction chemotherapy (T1) or during aplasia (T2) on complete remission (CR) rate, disease-free survival (DFS), and overall survival (OS) were retrospectively analyzed in 72 cases of de novo acute myeloid leukemia (AML) treated with HAD (homoharringtonine, cytosine arabinoside, and daunorubicin) regimen. The patients were separated into two subgroups by a cutoff of 10% bone marrow leukemic cells at T1 or T2 time point. The CR rate, DFS, and OS were significantly different between the two groups. We further confirmed that the percentage of RLCs at T1 or T2 is an independent prognostic factor of AML.

Pegfilgrastim-Induced Hyperleukocytosis

To report a pediatric case of pegfilgrastim-induced hyperleukocytosis. A 3-year-old boy with medulloblastoma therapy presented with white blood cell (WBC) count 0.1 x 10(3)/microL and absolute neutrophil count (ANC) 0.014 x 10(3)/microL on day 27 following a course of induction chemotherapy. The patient received pegfilgrastim 200 microg/kg the following day. On his return 6 days later for the next planned course of chemotherapy, hyperleukocytosis was determined, with WBC 149 x 10(3)/microL and ANC 110 x 10(3)/microL ("neutrophil overshoot"). No sources of the elevated WBC count other than administration of pegfilgrastim (eg, steroids, antiepileptics, infection) were present. Chemotherapy was delayed until the WBC count had fallen to 35.2 x 10(3)/microL (ANC 28.9 x 10(3)/microL). No sequelae from this adverse effect occurred. Pegfilgrastim has unique saturable neutrophil receptor-mediated clearance, the ability for self-regulation. Due to this clearance mechanism, hyperleukocytosis associated with pegfilgrastim use is uncommon in adults and has not been previously reported in pediatrics. The pegfilgrastim dose in children is under investigation; however, 100-110 microg/kg has been effective and safe in this population. Use of the Naranjo probability scale suggested that pegfilgrastim was the probable cause of hyperleukocytosis in our patient. Pegfilgrastim 200 microg/kg, in excess of the 100 microg/kg dose used in limited pediatric clinical trials, appeared to exceed saturable neutrophil receptor-mediated clearance. The inability of this mechanism to self-regulate neutrophil counts in the normal range led to neutrophil overshoot. Routine pediatric use of the pegylated dosage form of G-CSF should await further published clinical trials to validate a safe and effective dose.

Early Response to Platinum-Based First-Line Chemotherapy in Non-small Cell Lung Cancer May Predict Survival

Response rates in the palliative treatment of non-small cell lung cancer, with combination platinum-based chemotherapy, vary from 20% to 40%, leaving a large number with either stable or progressive disease. We examined radiographic response after two courses of platinum-based induction chemotherapy to see whether this is an early predictor of outcome. In this retrospective study, 320 patients with stage III/IV NSCLC were identified who received 4 or more courses of first-line platinum-based chemotherapy and attained partial response (PR) or stable disease (SD). After two courses, 115 patients attained PR and 205 SD. Cox regression analysis shows that response after two courses of chemotherapy remains an independent significant prognostic factor for survival. The 2-year survival for patients attaining PR after two courses (n = 115) was 23% compared with 11% (n = 205) for those with SD (p = 0.002). Patients who achieve an objective response after two courses also have a better symptomatic response (p = 0.003) and it was significantly longer (p = 0.04). Of the 205 with SD, 51 attained PR with four courses, whereas 154 (48%) remained with SD; there was no difference in survival outcome of these two groups. These data suggest that NSCLC patients who only have SD after two cycles of first-line chemotherapy have poorer survival outcome and less symptomatic benefit than those in PR. Trials looking at change in management at this point are warranted.

Prognostic value of change in CA 125 levels after the first cycle of induction chemotherapy for epithelial ovarian cancers: Results of a multicentric French study

16017 Background: CA 125 assays enable treatment-response monitoring in ovarian cancer. Patients and Methods: This multicentric study was performed to assess the predictive value with regard to pathologic complete response at surgical second look and the prognostic value of the serum CA 125 change (=rease [D], 50%, 25%, &lt; 25%ase) after one or two courses of induction chemotherapy (CT) with platinum salts and cyclophosphamide Of the 494 stage IIc - IV patients who were treated at the French Cancer Centres of Dijon, Bordeaux, Toulouse, Rouen, Reims, Nantes, Angers, Saint Cloud, 397 (80.4%d and 382 (77.3%om cancer. Median (range) follow up time was 34 months (3 - 215 months). Among them, 194 patients had a surgical second look. Results: The CA 125 change after the first, the second and the two first CT courses and CA 125 concentration (&gt; or =-1) before the third CT cycle had an univariate prognostic value for overall survival (OS) (p &lt; 0.0001 for both). In Cox models, CA 125 change after the first CT course (p &lt; 0.0001), residual tumour (p = CA 125 concentration before the second CT course (p =and patients’ age (p =were independent prognostic factors for OS. A normal CA 125 before each of the two first CT courses or a CA 125 decrease higher than 50%e first CT course with a CA 125 =-1 before the second CT course identify patients with good prognosis. Both criteria retained a significant value in predicting second-look findings by univariate and multivariate analysis (p &lt; 0.0001). Conclusion: Among well-established prognostic factors in ovarian cancers, the CA 125 change after the first CT course was independent prognostic factors for both achievement of pathological complete response and OS. No significant financial relationships to disclose.

A randomized trial of chemoradiotherapy versus surgery alone in patients with resectable esophageal cancer

4530 Background: The aim of this study was to compare survival in a randomized phase III trial of chemoradiotherapy (CHRT) versus surgery alone for localized resectable oesophageal cancer. Methods: Between 2000 and 2004, 91 patients with oesophageal cancer were enrolled in a Scandinavian multicenter study. Patients with resectable oesophageal squamous cell carcinoma (50%) or adenocarcinoma (50%) were randomized to chemoradiotherapy (CHRT) or surgery alone. Chemotherapy (CHT) was given in 3 cycles with cisplatin 100 mg/m2, day 1 and 5-fluorouracil 750 mg/m2/24 hours, infusion day 1–5, every three weeks. After one induction chemotherapy course, radiotherapy including the primary tumour and defined locoregional lymph nodes, was given concomitant with the following CHT cycles, to a total dose of 64 Gy, in 32 fractions. Surgery was performed according to Ivor Lewis and lymph nodes resected with standard two-field technique. Results: At a median follow-up of 51.8 month’s 65 deaths are noted. In the chemoradiation group 50% of the patients accomplished therapy according to protocol, 40% were treated with modifications of the protocol and radical resection was performed 76% of the patients. Median survival was 12.8 months for chemoradiation and 15.8 months for the surgery group. There was no significant difference in 1-year survival 56% and 55% for CHRT and surgery, respectively. By two years, survival curves diverge and 2-years survival was 37% (CI 95%: 23–51%) for the CHRT group and 25% (CI 95%: 12–39%) for the surgery group. At four years, survival was 29% for CHRT versus 23% for surgery (CI 95% CHRT: 16–43%, CI 95% Surgery: 10–36%). Both treatments were well tolerated and no treatment related deaths were recorded in any of the treatment arms. Most deaths were due to tumor disease (66%) in both groups. Conclusions: No statistically significant differences between the treatment arms were seen and survival results are equal to earlier reported. Both treatment arms were well tolerated. No significant financial relationships to disclose.

Prognostic factors for response to second induction course in patients showing persistent disease after first course of standard induction chemotherapy for de novo acute myeloid leukemia (AML)

7056 Background: Standard induction chemotherapy for AML consists of cytarabine plus daunorubicin or idarubicin (‘7+3' regimen). For patients showing persistent leukemia after first induction course (IND1) of the induction, usual practice is to give a second course (IND2) of similar regimen (‘7+3' or 5+2'). This strategy, however, has not been well evaluated. We investigated prognostic factors for response to IND2. Methods: We performed a retrospective study in 110 patients with de novo AML. All patients received cytarabine (100 or 200 mg/m2/d) for 7 days plus daunorubicin (45–60 mg/m2/d) or idarubicin (12 mg/m2/d) for 3 days as IND1. Patients who showed persistent leukemia after IND1 were given the same doses and drugs as ‘5+2’ (n = 85) or ‘7+3’ (n = 25) for IND2. We collected the clinico-pathologic data of the patients at diagnosis and at IND2, and analyzed prognostic factors for response to IND2. Results: Sixty-one (55.5%) of 110 patients, who received IND2, achieved complete remission (CR). The causes of treatment failure were resistant disease in 35, complication of aplasia in 8, and indeterminated in 6. Five-year probabilities of overall and relapse-free survival were 25% and 21%, respectively. Multivariate analysis demonstrated that cellularity at interim BM biopsy &gt; 30% (p = 0.015), blast percentage at interim BM aspiration &gt; 30% (p = 0.031), presence of circulating blasts at IND2 (p = 0.011), and unfavorable chromosomal abnormalities (p = 0.014) were independent risk factors for failure to induce CR. The CR rates were significantly different according to the number of the risk factors: 73% for 0–1 factor, 48% for 2 factors, and 11% for 3–4 factors (p&lt; 0.001). Conclusions: We identified 4 independent poor risk factors for CR in patients who showed persistent disease after standard induction chemotherapy and who received similar second induction course. Other treatment strategies such as high-dose cytarabine rather than standard regimens seem to be needed for the patients with 3–4 risk factors before IND2. No significant financial relationships to disclose.

Correlation between MDR1 genetic polymorphism and prognosis in acute myeloid leukemia

To assess the correlation of the multidrug resistance-1 (MDR1) gene single nucleotide polymorphisms (SNP) C1236T, G2677T/A and C3435T with the outcome of induction chemotherapy in patients with de novo acute myeloid leukemia (AML). A total of 44 AML patients were enrolled in this study. Genotype of MDR1 C1236T, G2677T/A and C3435T were analyzed with PCR/PFLP assay. Bone marrow smear was made at the end of the first induction chemotherapy to estimate whether complete remission (CR) has been achieved with the clinical characteristics. The Hardy-Weinberg equilibrium for the MDR1 C1236T, G2677T/A and C3435T were tested using a chi(2) analysis. Frequencies of genotype and allele in MDR1 C1236T, G2677T/A and C3435T were compared using a chi(2) test or Fisher's test in terms of the clinical characteristics or achievement of CR. There were significant differences among ethnicities in exon 12, 21, 26, but which were not between healthy chinese volunteers and AML patients. The CR rate of the group with the number of white blood cells (WBC) < 10 x 10(9)/L were significantly higher than that of the group with WBC > 10 x 10(9)/L (chi(2) = 7.207, P = 0.007). There was no correlation between the MDR1 C1236T and C3435T and CR rate (P = 0.349, P = 0.074), but MDR1 G2677T/A genetic polymorphisms were strong associated with the probability of CR (chi(2) = 6.214, P = 0.045). In addition, the CR was lower in G/G genotype at -2677 than non G/G genotype (chi(2) = 6.142, P = 0.013), and was lower in C/T genotype at -3435 than non C/T genotype (chi(2) = 3.991, P = 0.046), even lower than T/T genotype (chi(2) = 5.134, P = 0.023). With important prognostic significance, MDR1 genetic polymorphisms, such as G2677T/A can predict whether complete remission can be achieved after the first course of induction chemotherapy.

Change in CA 125 levels after the first cycle of induction chemotherapy is an independent predictor of epithelial ovarian tumour outcome

CA 125 assays enable treatment response monitoring in ovarian cancer. This multicentric study was carried out to assess the prognostic value of the CA 125 change after the first and the second courses of induction chemotherapy (CT). Of the 494 stage IIc-IV patients, 194 had a surgical second look, 397 (80.4%) relapsed and 382 (77.3%) died from cancer. Median (range) follow-up time was 34 months (3-215 months). In Cox models, CA 125 change after the first course (P < 0.0001), residual tumour (P = 0.003), CA 125 before the second course (P = 0.025) and patients' age (P = 0.048) were independent prognostic factors for overall survival (OS). A normal CA 125 before each of the two first CT courses or a CA 125 decrease >50% after the first course with a normal CA 125 before the second course identify patients with good prognosis. Both criteria retained a significant value in predicting second-look findings by univariate and multivariate analysis (P < 0.0001). Among well-established prognostic factors in ovarian cancers, the CA 125 change after first course of CT was independent prognostic factors for both achievement of pathological complete response and OS.

Indeterminate cell histiocytosis in association with later occurrence of acute myeloblastic leukaemia

Indeterminate cell histiocytosis (ICH) is a proliferation of indeterminate CD1a+, CD68+, S100+ and CD207- dermal dendritic cells. We describe a 39-year-old man who developed diffuse ICH and, 6 years later, acute myeloblastic leukaemia (AML). He was treated with cyclophosphamide, etoposide and vinblastine until 2003. In August 2004, he presented dyspnoea, hyperpyrexia and infiltration of the lung parenchyma, compatible with an AML invasion, and died after a course of induction chemotherapy. Cytomorphology and immunophenotype analyses suggested an ICH clonal evolution. The leukaemogenic role of etoposide is discussed. ICH has previously been reported in association with B-cell malignancy, but only one case has shown systemic progression.

Acute Lymphoblastic Leukemia Occurring in Patient with Acute Myeloid Leukaemia: An Unrelated Leukemia Rather Than a Therapy-Related Malignancy. About 2 Cases.

Introduction: Therapy-related acute myeloid leukaemia (AML) is a well known event which can occur few years after a chemotherapy with alkylating agents or topoisomerase II inhibitors received for primary malignancies such as Hodgkin and non-Hodgkin lymphomas, Acute lymphoblastic leukaemia (ALL) or solid tumors. More exceptional are acute B or T-ALL following AML (11 cases in literature so far, Liso et al, Haematologica, 1998; Leung et al, Leukemia, 2001; Tsuboi et al, Int J Hematol, 2003) raising the question of the origin of this second event. Among 1486 AML cases diagnosed between 1985 and 2006 in our institution, we report only 2 cases of B-cell ALL occurring 1 and 19 years after AML.Case1: A 36-year-old man was admitted in our institution in 1985. The peripheral blood examination showed: Hemoglobin level 6.2 g/dL, leukocyte count 27.8 *109/L with 32% of monocytes and platelet count 52 *109/L. Blast cell infiltrate was 40% on blood and 55% on bone marrow smears, with 80% exhibiting myeloperoxydase (MPO) activity. Morphology was typical of FAB-M4 AML with eosinophil subtype. Unfortunately, phenotype and caryotype evaluations were not performed. Patient was treated according to POF trial. Complete Remission (CR) was achieved after induction therapy and persisted 19 years after 3 consolidations. In 2004, blast cells reappeared in the blood (7%) and bone marrow (96%) aspirates Interestingly, MPO activity was negative and flow cytometer analysis revealed a CD19+ CD10+ TdT+ CD79a+ (EGIL-BII) B-Cell Precursor (BCP) ALL immunophenotype with only the sole CD13+ myeloid marker expression. Cytogenetic studies showed a hypodiploidy (33–35 chromosomes) without Bcr-Abl and MLL rearrangements. Patient achieved CR after induction chemotherapy according to GRAALL2003 trial. He then received consolidation by high-dose methotrexate but develop a polyneuropathy and died rapidly.Case2: A AML, FAB-M5B subtype, was first diagnosed in 2005 in a 48-year-old woman. Hemoglobin level was 10.4 g/dL, leukocyte count 73.2 *109/L with 79.5% of abnormal monocytic cells and platelet count 100 *109/L. Typically, monoblastic bone marrow cells (71%) showed a low (5%) MPO and a strong (80%) butyrate activities, together with a CD13+ CD14+ CD15+ CD33+ CD34+ CD36+ CD65+ CD117− immunophenotype without B-cell marker expression. Cytogenetic analysis showed no caryotypic abnormalities. The patient was treated according to LAM2001 trial and CR was achieved after 2 courses of induction chemotherapy. The patient was autografted in October 2005. She presented with a pancytopenia in April 2006 and the diagnosis of BCP-ALL was made. The bone marrow was infiltrated with 76.5% of MPO negative, butyrate negative blasts exhibiting a CD19+ CD10−CD79a+TdT+ (EGIL-BI/Pro-B subtype without any myeloid marker expression. Cytogenetic analysis showed a t (4;11) (q21;q23) with MLL rearrangement on 44% of the blasts. The patient achieved CR after induction therapy according to GRAALL2003 trial but developed a disseminated fusariosis. She is still alive in CR but due to the persistence of the infectious complication, she has not yet received consolidation.Conclusion: Our study shows that ALL occurring after AML is a very occasional event. Prognosis seems poor related to treatment toxicity. We found no argument supporting a link between both leukaemia subtypes or a relationship with therapy. Additional cases are warranted to determine if this association is unrelated or not.