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Allogeneic hematopoietic cell transplantation (HCT) during chemotherapy-induced aplasia may offer long-term survival in acute myeloid leukemia (AML) with otherwise poor prognosis including ELN adverse risk, relapsed or refractory disease. However, the value of residual morphologic disease prior HCT in this context has not been conclusively settled until yet. Therefore, we aimed to investigate variables predicting outcome in this unique setting of sequential conditioning therapy, with a focus on pretreatment morphologic blast count. In contrast to the most popular FLAMSA-RIC protocol, we used a melphalan-based conditioning regimen during aplasia.We retrospectively analyzed data from 173 AML patients who underwent a sequential melphalan-based conditioning therapy between 2003 and 2015 at our centre. All patients participated either in the prospective Phase 2 BRIDGE trial (NCT01295307), the Phase 3 AML2003 study (NCT00180102) or were treated according to this protocol and underwent allogeneic HCT after melphalan-based conditioning in treatment-induced aplasia.Median bone marrow blast count prior to conditioning was 10% (range, 0-96%). Four year probabilities of EFS and OS were 34% (95% CI, 28-43%) and 43% (95% CI, 36-52%), respectively. In multivariate analysis, blast count20% was associated with worse EFS (HR = 1.93;Allogeneic HCT in aplasia with a melphalan-based conditioning regimen has the potential to cure a subset of adverse risk AML patients, even with persistent morphological disease prior HCT. However, a high pre-transplant blast count still indicates patients with a dismal prognosis, especially in the relapsed patient group, for whom post-transplant strategies should be considered to further optimize post HCT outcome.

Isolation of mesenchymal stromal cells (MSCs) from pretreated, hematologic patients is challenging. Especially after allogeneic hematopoietic cell transplantation (HCT), standard protocols using bone marrow aspirates fail to reliably recover sufficient cell numbers. Because MSCs are considered to contribute to processes that mainly affect the outcome after transplantation, such as an efficient lymphohematopoietic recovery, extent of graft-versus-host disease as well as the occurrence of leukemic relapse, it is of great clinical relevance to investigate MSC function in this context. Previous studies showed that MSCs can be isolated by collagenase digestion of large bone fragments of hematologically healthy patients undergoing hip replacement or knee surgeries. We have now further developed this procedure for the isolation of MSCs from hematologic patients after allogeneic HCT by using trephine biopsy specimens obtained during routine examinations. Comparison of aspirates and trephine biopsy specimens from patients after allogeneic HCT revealed a significantly higher frequency of clonogenic MSCs (colony-forming unit–fibroblast [CFU-F]) in trephine biopsy specimens (mean, 289.8 ± standard deviation 322.5 CFU-F colonies/1 × 106 total nucleated cells versus 4.2 ± 9.9; P

Cytarabine is an effective drug in the treatment of haematological malignancies. The therapy is associated with various complications. Frequencies of dermatological side-effects range from 2–72% and occur most commonly after high-dose regimens. Although most cutaneous reactions are mild and resolve spontaneously within several days, they may result in an increased risk of infection and alterations in comfort. In some cases, severe life-threatening reactions have been reported. Here we describe the case of a patient with acute myeloid leukaemia, who developed severe exceptional skin toxicity in terms of auricular oedema and palmar dyshidrotic eczema after the application of low-dose cytarabine. Re-administration of the drug resulted in reduced skin toxicity during further cycles of chemotherapy. Negative epicutaneous patch-testing supported the existence of cytarabine-provoked toxicity.

Background Neuronal plasticity leading to evolving reorganization of the neuronal network during entire lifespan plays an important role for brain function especially memory performance. Adult neurogenesis occurring in the dentate gyrus of the hippocampus represents the maximal way of network reorganization. Brain radio-chemotherapy strongly inhibits adult hippocampal neurogenesis in mice leading to impaired spatial memory. Methods To elucidate the effects of CNS radio-chemotherapy on hippocampal plasticity and function in humans, we performed a longitudinal pilot study using 3T proton magnetic resonance spectroscopy (1H-MRS) and virtual water-maze-tests in 10 de-novo patients with acute lymphoblastic leukemia undergoing preventive whole brain radio-chemotherapy. Patients were examined before, during and after treatment. Results CNS radio-chemotherapy did neither affect recall performance in probe trails nor flexible (reversal) relearning of a new target position over a time frame of 10 weeks measured by longitudinal virtual water-maze-testing, but provoked hippocampus-specific decrease in choline as a metabolite associated with cellular plasticity in 1H-MRS. Conclusion Albeit this pilot study needs to be followed up to definitely resolve the question about the functional role of adult human neurogenesis, the presented data suggest that 1H-MRS allows the detection of neurogenesis-associated plasticity in the human brain.

Several groups have reported results from smaller series of AYAs with ALL. Outcomes with so-called protocols for adults were generally inferior compared to so-called pediatric protocols. The GMALL protocols were originally based on pediatric BFM protocols and have been consecutively optimized for adults since 1981. We report the results of two recent protocols 05/93 (Goekbuget et al, Blood 98(11):802a, 2001) and 07/03 (Goekbuget et al, Blood 110(11):12a, 2007). In study 07 high risk (HR) pts were identified by one of the factors: B-lin with WBC>30.000, late CR (>3 wks), pro-B, early T, mature T, MLL1/AF4/t(4;11). Pts without risk factors were standard risk (SR) and those with BCR-ABL/t(9;22) very high risk (VHR). HR/VHR pts were candidates for SCT in CR1. The major innovations in study 07 were: intensified, shortened induction with dexamethasone instead of prednisone, PEG-asparaginase (ASP) instead of native ASP, intensified first consolidation, 6x HDMTX/ASP during consolidation, matched unrelated SCT for HR/VHR pts without sibling donor and SCT indication in pts with persistent MRD. After amendments in trial 07 pts partly also received intensified PEG-ASP, rituximab in CD20+ ALL and imatinib in Ph+ ALL. Overall, 1529 of 3060 (50%) pts recruited into both trials were aged between 15-35 yrs. 642 pts from 94 centres were recruited to study 05 and 887 pts from 130 centres to study 07. Patient characteristics were similar for both trials. 70% had B-Lin and 30% T-ALL (61% c/preB, 9% proB, 7% early T, 6% mature T, 17% thy T) with no significant differences across age subgroups (15-17,18-25 and 26-35 yrs). Allocation to SR, HR and VHR was 51%, 35% and 14%. VHR incidence increased from 3%, 11% to 19% in age groups (p The CR rate increased in studies 05 to 07 from 88% to 91% (p=.001), most prominently within the age range of 26-35 yrs (86% to 90%;p=.001) (table). The OS increased from 46% to 65% (p.05). OS increased in SR (58% to 74%; p 15% vs 43% of all CR pts underwent SCT in CR1 in studies 05 and 07. The proportion of SCT increased from 22% to 68% (p In trial 07 MRD in week 16 (after consolidation I) was tested in 353 pts. The proportion of molecular failure (MRD>0.01%) was 26% with no differences across age groups. OS was 90% in pts with mol. CR vs 53% in mol. failure (p We present here results of the so far largest cohort of AYA ALL pts treated according to pediatric-derived adult ALL protocols. Outcomes have significantly improved and reached a 73% OS in pts aged 15-17 yrs. Intensified treatment with ASP, MTX and targeted therapies as rituximab and imatinib and MRD based stratification have contributed to the improvement in study 07. SCT led to improved OS in HR and VHR ALL. Obviously, there is no indication for SCT in CR1 in young SR pts with an OS of 74%. Future GMALL studies will attempt to optimize further the combination of pediatric approaches and targeted therapies in adults. Supported by Deutsche Krebshilfe 70-2657-Ho2 and partly BMBF 01GI 9971. Disclosures: Off Label Use: RItuximab in ALL.