This study's findings indicate that adolescents should be included in intensive pediatric protocols and that new trials should be designed, inspired by pediatric protocols, for the treatment of young adults with ALL.
and overall survival were 30%, 51%, and 65%, respectively. These 3 end points compared very favorably with results obtained in the pre-imatinib LALA-94 trial. This study confirms the value of the combined approach and encourages prospective trials to define the optimal chemotherapy that has to be combined with imatinib and to carefully reevaluate the place of allogeneic SCT in this new context. (Blood.
Bone marrow involvement by anaplastic large cell anaplastic large cell (ALC) lymphoma can be difficult to detect on routine morphologic examination alone. In a series of 42 patients with ALC lymphoma, the authors analyzed: (1) the usefulness of a limited panel of monoclonal antibodies directed against CD30 (Ber-H2, HRS4) and epithelial marrow involvement on routinely processed biopsy specimens; and (2) the prognostic significance of bone marrow involvement as detected on both morphologic and immunohistochemical grounds. On conventional examination, 17% of the patients were found to have bone marrow involvement at diagnosis. However, after immunohistochemical analysis, occult malignant cells were detected in 23% of the patients with negative bone marrow biopsy on routine histology. The low percentage of positive cases on routine morphologic examination compared to immunohistochemical examination was related to: (1) the scarcity of neoplastic cells which were scattered among hematopoietic cells; (2) the difficulty of distinguishing malignant cells from immature hematopoietic elements; and (3) the absence of alteration of the reticulin network. The authors observed a significant association between marrow infiltration and the presence of hematologic abnormalities (mostly anemia or cytopenias) at diagnosis, both in children and adult patients. More importantly, a significant lower survival was seen in patients with bone marrow involvement compared to those without bone marrow involvement. Immunohistochemistry with anti-CD30 and anti-EMA antibodies should be performed systematically in bone marrow biopsies from patients with ALC lymphoma to reliably identify the presence of bone marrow involvement that appears to carry a poor prognosis.
Unlike cytarabine, cellular entry of Elacytarabine, the elaidic acid ester derivative of cytarabine, is independent of the human equilibrative nucleoside transporter 1 (hENT1). This phase II study tested whether the hENT1 blast expression level can be used as a predictive marker for cytarabine response and if the efficacy of elacytarabine is independent of hENT1 expression. A total of 51 patients with acute myeloid leukemia (AML) induction failure were given elacytarabine-idarubicin as a second induction course. The hENT1 expression level was analyzed prior to first induction and/or prior to treatment with elacytarabine. The overall response rate (ORR) was 41% and the safety profile was manageable. There is a trend suggesting that hENT1 expression influences response to cytarabine, but not sufficient to support it as a biomarker for guiding treatment. Further, we conclude that the activity of elacytarabine is not significantly predicted by the hENT1 expression level.
Background
The typical sign of intracranial hypotension (IH) is postural headache. However, IH can be associated with a large diversity of clinical or radiological signs leading to difficult diagnosis especially in case of coma. The association of cerebral venous thrombosis (CVT) and subdural hemorrhage is rare but should suggest the diagnosis of IH.
Methods
Case report.
Case Description
We report here a case of comatose patient due to spontaneous IH complicated by CVT and subdural hemorrhage. The correct diagnosis was delayed due to many confounding factors. IH was suspected after subdural hemorrhage recurrence and confirmed by magnetic resonance imaging (MRI). After 2 epidural patches with colloid, favorable outcome was observed.
Discussion
The most common presentation of IH is postural orthostatic headaches. In the present case report, the major clinical signs were worsening of consciousness and coma, which are a rare presentation. Diagnosis of IH is based on the association of clinical history, evocative symptomatology, and cerebral imaging. CVT occurs in 1‐2% of IH cases and the association between IH, CVT, and subdural hemorrhage is rare. MRI is probably the key imaging examination. In the present case, epidural patch was performed after confounding factors for coma had been treated. Benefit of anticoagulation had to be balanced in this case with potential hemorrhagic complications, especially within the brain.
Conclusion
Association of CVT and subdural hemorrhage should lead to suspect IH. Brain imaging can help and find specific signs of IH.
In a large series of patients with Ph1-ALL treated in the LALA-94 trial, negative BCR-ABL minimal residual disease (MRD) and allogeneic donor availability were two independent good-risk factors for survival in those reaching hematological complete remission (HCR) after standard induction followed by intensive HAM consolidation (Dombret et al. Blood2002;100:2357). The HAM regimen included intermediate-dose cytarabine (1 g/m2/12h Day 1 to 4) and mitoxantrone (10 mg/m2 Day 3 to 5). The fraction of HCR patients in molecular CR (MCR) after HAM was 38%, with a median RT-PCR sensitivity of 10−5. In the present Phase I/II study, we combined increasing dosages of imatinib with HAM (HAMI regimen) in an attempt: 1) to increase the fraction of MCR patients from 38 to 75% (as primary objective); and 2) to evaluate the safety of the combination regimen and the feasibility of autologous peripheral blood stem cell (PBSC) collection after HAMI (as secondary objectives). Patients aged 18–60 years with Ph1-ALL in HCR after 1 or 2 cycles of chemotherapy were eligible in the absence of counter-indication for further stem cell transplantation. Imatinib was administered daily from Day 1 of HAM. MRD was assessed by RQ-PCR at Day 0 and Day 45 of HAMI. MCR was defined as a BCR-ABL level lower than 10−5 at Day 45. Twenty-two patients have been enrolled. Results observed in the first 18 patients treated in 3 consecutive 6-patient cohorts at 400, 600, and 800 mg/d imatinib, respectively, are available. Main results may be summarized as follows: 1) an excessive toxicity was observed in the 800 mg/d cohort leading to recommend the 600 mg/d dosage for further combinations of imatinib and intensive chemotherapy; 2) only 5 of the 15 patients tested (33%) reached MCR at Day 45 of HAMI and no clear correlations were found between molecular response and imatinib dosage or Day 0 MRD level; 3) after HAMI, PBSC collection was feasible under imatinib administration in 9 out of 14 patients (64%) with an apparent relationship between failure to collect and no MCR (P=.08); 4) only 3 patients were not able to receive allogeneic or autologous transplantation as further consolidation (1 early relapse, 1 severe infection, 1 too high MRD level); and 5) estimated 18-month disease-free and overall survival were 58% and 78%, respectively, with 8/15 patients receiving imatinib during the post-transplant period. In conclusion, failure to improve the MCR rate as compared to our no-imatinib historical control could be explained by the relatively short exposure to imatinib and/or by the absence of in vivo synergism between imatinib and cytarabine or mitoxantrone. More benefit might be anticipated by incorporating imatinib earlier in the treament i.e. first induction course. Further studies are needed to evaluate the role of post-transplant maintenance with imatinib.
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