tbuckley/cabot-search huggingface dataset:
Ugly Duckling Sign as a Major Factor of Efficiency in Melanoma Detection
Authors: Caroline Gaudy-Marqueste, Yanal Wazaefi, Yvane Bruneu, Raoul Triller, Luc Thomas, Giovanni Pellacani, Josep Malvehy, Marie-Françoise Avril, Sandrine Monestier, Marie-Aleth Richard, Bernard Fertil, Jean-Jacques Grob
Journal: JAMA Dermatology (2017)

Understanding the contribution of the ugly duckling sign (a nevus that is obviously different from the others in a given individual) in intrapatient comparative analysis (IPCA) of nevi may help improve the detection of melanoma.To assess the agreement of dermatologists on identification of the ugly duckling sign and estimate the contribution of IPCA to the diagnosis of melanoma.The same 2089 digital images of the nevi of a sample of 80 patients (mean age, 42 years [range, 19-80 years]; 33 men and 47 women), as well as 766 dermoscopic images from a subset of 30 patients (mean age, 40 years [range, 21-75 years]; 12 men and 18 women), were randomly presented to the same 9 dermatologists for blinded assessment from September 22, 2011, to April 1, 2013. The first experiment was designed to mimic an IPCA situation, with images of all nevi of each patient shown to the dermatologists, who were asked to identify ugly duckling nevi (UDN). The second experiment was designed to mimic a lesion-focused analysis to identify morphologically suspicious nevi. Data analysis was conducted from November 1, 2012, to June 1, 2013.Number of nevi labeled UDN and morphologically suspicious nevi, specificity of lesion-focused analysis and IPCA, and number of nevi identified for biopsy.Of the 2089 clinical images of nevi from 80 patients (median number of nevi per patient, 26 [range, 8-81]) and 766 dermoscopic images (median number of nevi per patient, 19 [range, 8-81]), all melanomas were labeled UDN and as morphologically suspicious nevi by the 9 dermatologists. The median number of UDN detected per patient was 0.8 among the clinical images of nevi (mean, 1.0; range, 0.48-2.03) and 1.26 among the dermoscopic images (mean, 1.4; range, 1.00-2.06). The propensity to consider more or fewer nevi as having ugly duckling signs was independent of the presentation (clinical or dermoscopic). The agreement among the dermatologists regarding UDN was lower with dermoscopic images (mean pairwise agreement, 0.53 for clinical images and 0.50 for dermoscopic images). The specificity of IPCA was 0.96 for clinical images and 0.95 for dermoscopic images vs 0.88 and 0.85, respectively, for lesion-focused analysis. When both IPCA and lesion-focused analyses were used, the number of nevi considered for biopsy was reduced by a factor of 6.9 compared with lesion-focused analysis alone.Intrapatient comparative analysis is of major importance to the effectiveness of the diagnosis of melanoma. Introducing IPCA using the ugly duckling sign in computer-assisted diagnosis systems would be expected to improve performance.
At-home Dosing Adherence During Characterized Oral Desensitization Immunotherapy (CODIT) for Peanut Allergy
Authors: Stacie M. Jones, Brian P. Vickery, J. Andrew Bird, Jonathan M. Spergel, Rima A. Rachid, Amal H. Assa'ad, Julie Wang, Stephanie A. Leonard, Susan Stefanac Laubach, Edwin Kim, Benjamin P. Davis, Michael Welch, Jennifer Heimall, Antonella Cianferoni, Andrew J. MacGinnitie, Elena Crestani, Amr Radwan, Andrea Vereda, Daniel C. Adelman, A. Wesley Burks
Journal: Journal of Allergy and Clinical Immunology (2017)
MDR1 C3435T Polymorphism Is Highly Correlated with Early Response to Therapy and Outcome in Childhood Acute Lymphoblastic Leukaemia: Malaysia-Singapore 2003 ALL Study.
Authors: Shirley Kow Yin Kham, Hany Ariffin, Yiong Huak Chan, Thuan Chong Quah, Allen Eng Juh Yeoh
Journal: Blood (2007)
Splanchnic Vein Thrombosis Associated with Myeloproliferative Neoplasms: A Study of the AGIMM &amp; IWG-MRT Groups in 519 Subjects
Authors: Lisa Pieri, Paola Guglielmelli, Massimo Primignani, Silvia Betti, Maria Luigia Randi, Elisa Rumi, Cristiana Pascutto, Francisco Cervantes, Martin Ellis, Frederick Chen, Federica Delaini, Claire N Harrison, Giorgina Specchia, Heinz Gisslinger, Nicola Vianelli, Marco Ruggeri, Francois Girodon, Alberto Bosi, Claudia Santarossa, Alessandra Carobbio, Maya Koren-Michowitz, Noa Lavi, Dhiraj Tripathi, Neil Rajoriya, Ravi Gupta, Elena Rossi, Natalia Curto Garcia, Alessandra Ricco, Bettina Gisslinger, Nicola Polverelli, Mario Cazzola, Valerio De Stefano, Tiziano Barbui, Ayalew Tefferi, Alessandro Maria Vannucchi
Journal: Blood (2014)
Abstract 13456: Screening for Transthyretin Cardiac Amyloidosis Using 99mTc-Pyrophosphate Scintigraphy in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: David L Narotsky, Susheel K Kodali, Mathew S Mauer, Sabahat Bokhari, Nadira Hamid, Ted Pozniakoff, Richard Weinberg, Tamim M Nazif, Isaac George, Torsten Vahl, Rebecca T Hahn, Adam Castano
Journal: Circulation (2015)

Background: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure with preserved ejection fraction (EF). Bone scintigraphy has emerged as a non-invasive imaging approach that is highly sensitive and specific for identifying ATTR-CA. We conducted a prospective cohort study using 99m Tc-pyrophosphate scintigraphy ( 99m Tc-PYP) to determine the prevalence of ATTR-CA and other clinical associations with 99m Tc-PYP positivity in older patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods: A total of 40 patients (53% men) with severe AS underwent 99m Tc-PYP planar cardiac imaging within 30 days of TAVR. Myocardial uptake was assessed with both a semi-quantitative visual score (range 0: no uptake to 3: uptake greater than bone) and by quantitative analysis by drawing a region of interest over the heart, mirroring it to the contralateral chest, and calculating a heart-to-contralateral ratio (HCL). Semi-quantitative score ≥ 2 and HCL ≥ 1.5 were considered positive for ATTR-CA. Demographics and pre-TAVR clinical history, laboratory values, EKG, and echocardiographic data were also analyzed for association with 99m Tc-PYP positivity. Results: Among 40 patients (mean age 85.2 + 5.3 years), 99m Tc-PYP uptake was found in 10% (n=4), all men. Mean semi-quantitative score was 2.8±0.5 and HCL was 1.6±0.1. Elevated BNP (1379±689 vs 438±483 pg/ml, p=0.02), decreased serum albumin (3.2±0.5 vs 3.8±0.5 g/dL, p=0.02), and both larger interventricular septal wall (1.3±0.4 vs 1.0±0.2 cm, p=0.01) and left posterior wall thickness (1.3±0.6 vs 0.9±0.2 cm, p=0.04) at diastole were associated with 99m Tc-PYP positivity. There was no difference in EF, but myocardial contraction fraction, the ratio of stroke volume to myocardial volume, was significantly lower, 24±12% vs 45±18%, in 99m Tc-PYP positive patients (p=0.03). Conclusions: 99m Tc-PYP has potential as a screening tool for ATTR-CA in high-risk populations. Our data suggest that ATTR-CA may be prevalent in patients undergoing TAVR, particularly men, 20% of whom had a positive 99m Tc-PYP scan. Identifying specific etiologies of heart failure in TAVR patients may be important for prognostication and response to therapy.
Holmium-166 (166Ho)-DOTMP Skeletal Targeted Radiotherapy (STR™) with Melphalan and Autologous Peripheral Stem Cell Transplant (PBSCT) for Multiple Myeloma (MM).
Authors: Mark Goodman, William I. Bensinger, Sergio Giralt, Donna Salzman, Katherine L. Ruffner, Hazel B. Breitz
Journal: Blood (2004)
Hematopoietic Stem-Cell Transplantation for Advanced SystemicMastocytosis
Authors: C. Ustun, A. Reiter, B. Scott, R. Nakamura, G. Damaj, S. Kreil, R. Shanley, W. Hogan, Perales, T. Shore, H. Baurmann, R. Stuart, B. Gruhn, Michael Doubek, J. Hsu, E. Tholouli, T. Gromke, L. Godley, L. Pagano, A. Gilman, E.M. Wagner, T. Shwayder, M. Bornhauser, E. Papadopoulos, A. Bohm, G. Vercellotti, M.T. Van Lint, Ch. Schmid, W. Rabitsch, V. Pullarkat, F. Legrand, I. Yakoub-agha, W. Saber, J. Barrett, O. Hermine, H. Hagglund, W. Sperr, U. Popat, E. Alyea, S. Devine, H.J. Deeg, D. Weisdorf, C. Akin, P. Valent
Journal: Journal of Clinical Oncology (2014)

Purpose Advanced systemic mastocytosis (SM), a fatal
hematopoietic malignancy characterized by drug resistance, has
no standard therapy. The effectiveness of allogeneic
hematopoietic stem-cell transplantation (alloHCT) in SM remains
unknown. Patients and Methods In a global effort to define the
value of HCT in SM, 57 patients with the following subtypes of
SM were evaluated: SM associated with clonal hematologic
non–mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia
(MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of
patients was 46 years (range, 11 to 67 years). Donors were
HLA-identical (n = 34), unrelated (n = 17), umbilical cord
blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3).
Thirty-six patients received myeloablative conditioning (MAC),
and 21 patients received reduced-intensity conditioning (RIC).
Results Responses in SM were observed in 40 patients (70%),
with complete remission in 16 patients (28%). Twelve patients
(21%) had stable disease, and five patients (9%) had primary
refractory disease. Overall survival (OS) at 3 years was 57%
for all patients, 74% for patients with SM-AHNMD, 43% for those
with ASM, and 17% for those with MCL. The strongest risk factor
for poor OS was MCL. Survival was also lower in patients
receiving RIC compared with MAC and in patients having
progression compared with patients having stable disease or
response. Conclusion AlloHCT was associated with long-term
survival in patients with advanced SM. Although alloHCT may be
considered as a viable and potentially curative therapeutic
option for advanced SM in the meantime, given that this is a
retrospective analysis with no control group, the definitive
role of alloHCT will need to be determined by a prospective
trial.
Mitogenome Diversity in Sardinians: A Genetic Window onto an Island's Past
Authors: Anna Olivieri, Carlo Sidore, Alessandro Achilli, Andrea Angius, Cosimo Posth, Anja Furtwängler, Stefania Brandini, Marco Rosario Capodiferro, Francesca Gandini, Magdalena Zoledziewska, Maristella Pitzalis, Andrea Maschio, Fabio Busonero, Luca Lai, Robin Skeates, Maria Giuseppina Gradoli, Jessica Beckett, Michele Marongiu, Vittorio Mazzarello, Patrizia Marongiu, Salvatore Rubino, Teresa Rito, Vincent Macaulay, Ornella Semino, Maria Pala, Gonçalo R Abecasis, David Schlessinger, Eduardo Conde-Sousa, Pedro Soares, Martin B Richards, Francesco Cucca, Antonio Torroni
Journal: Molecular Biology and Evolution (2017)

Sardinians are "outliers" in the European genetic landscape and, according to paleogenomic nuclear data, the closest to early European Neolithic farmers. To learn more about their genetic ancestry, we analyzed 3,491 modern and 21 ancient mitogenomes from Sardinia. We observed that 78.4% of modern mitogenomes cluster into 89 haplogroups that most likely arose in situ. For each Sardinian-specific haplogroup (SSH), we also identified the upstream node in the phylogeny, from which non-Sardinian mitogenomes radiate. This provided minimum and maximum time estimates for the presence of each SSH on the island. In agreement with demographic evidence, almost all SSHs coalesce in the post-Nuragic, Nuragic and Neolithic-Copper Age periods. For some rare SSHs, however, we could not dismiss the possibility that they might have been on the island prior to the Neolithic, a scenario that would be in agreement with archeological evidence of a Mesolithic occupation of Sardinia.
A phase II trial of high-dose radiotherapy (60 Gy) and UFT/l-leucovorin in patients with locally advanced rectal cancer (LARC): Long-term results
Authors: C. Qvortrup, A. Jakobsen, F. Hansen, G. Baatrup, C. Bisgaard, P. Rasmussen, P. Pfeiffer
Journal: Journal of Clinical Oncology (2004)

3590 Background: Preoperative chemoradiotherapy is a cornerstone in patients (pts) with non-resectable LARC. To improve outcome (number of R0 resections and survival) radiotherapy (RT) was combined with oral UFT/l-leucovorin and a long delay to allow tumour regression before radical intended surgery. Methods: Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT pts received a daily dose of oral UFT 300 mg/m2 plus l-leucovorin 22.5 mg 5/7days (divided in three doses). Results: From April 1998 to June 2003, 50 pts (median age 61 years (31–83); median PS 0 (0–2) with LARC (34 primary, 16 recurrent) were treated. All pts received the planned 60 Gy, median duration of RT was 43 days (39–49). Toxicity was very modest, only 3 pts had a dose reduction of UFT. No hematological toxicity was seen at all. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or dysuria) was frequently observed but only 3 pts experienced grade 3 toxicity (diarrhoea and/or nausea/vomiting). 39 pts (78%) were operated (30 R0, 5 R1, 4 R2) 47 days (17–112) after completion of RT. Five (10%) pts had a pathological complete response (pCR). 14 pts died after median 12 (3–28) months. 36 pts are alive (median follow-up 22 months). Conclusions: Preoperative high-dose RT and UFT in LARC produces not only pCR but it also allows radical surgery and thus a chance of cure in more than 50% of the patients. No significant financial relationships to disclose.
SURG-31. INTRAOPERATIVE MOLECULAR DIAGNOSIS AND SURGICAL GUIDANCE USING iKNIFE REAL-TIME MASS SPECTROMETRY
Authors: Babar Vaqas, Emma White, Ho Hui-Yu, Julia Balog, Dieter Galea, Zoltan Takats, Kevin O’Neill
Journal: Neuro-Oncology (2016)

Mass spectrometry offers a novel dimension-rich modality to characterize brain tumors and guide surgery in real-time. It seamlessly integrates with traditional biopolar forceps to offer a level of tissue analysis never available before to the surgeon. We evaluate the use of the iKnife in 40 patients undergoing craniotomy for brain tumors. A single centre prospective observational study was designed involving a consecutive series of 40 patients undergoing craniotomy and resection of a range of brain tumors. A neuronavigation system was used to register iKnife readings. Precise intraoperative readings from different tumor zones were taken and compared to matched core biopsy samples verified by routine histopathology. Ex-vivo tissue samples from these cases were also analysed. Multivariate statistics including PCA/LDA analysis was used to analyse the mass spectra obtained and compare these to the histological data. The system correctly identified normal versus tumor tissue in ex-vivo samples, this was then used to inform the in-vivo sample analysis. The system was able to correctly characterise the different brain tumors in the study including meningiomas, metastases as well as intrinsic low grade and high grade gliomas. IDH mutation status was identifiable using the iKnife. The iKnife represents a system which can accurately and rapidly identify tissue being operated on and easily integrates with the current setup in all operating rooms. The information is collected during routine use of bipolar forceps raising the possibility of controlling tumor resection using the real-time molecular data being obtained. Further multicentre studies are required to investigate patient-patient and machine-machine variability.
Clinical, pathologic, and molecular characteristics of patients with non-small cell lung cancer harboring mutations in <i>PIK3CA</i>.
Authors: M. C. Pietanza, M. E. Arcila, J. E. Chaft, M. F. Zakowski, M. Ladanyi, G. J. Riely, M. G. Kris
Journal: Journal of Clinical Oncology (2011)

7587 Background: PIK3CA encodes the p100a subunit of the mitogenic signaling protein phosphatidylinositol 3-kinase (PI3K). PI3K is a RAS-activated tyrosine kinase that signals through downstream mediators including AKT and m-TOR. PIK3CA mutations in the helical binding domain and catalytic subunit are implicated in tumorigenesis and treatment resistance in many cancers. The clinical characteristics of patients with PIK3CA-mutant lung cancer have not been reported. Methods: To identify patients with NSCLC harboring PIK3CA mutations, we examined results of routine assessment of histology and driver mutations in EGFR, KRAS, BRAF, HER2, PIK3CA, AKT1, NRAS, MEK1, and EML4-ALK (Kris, Proc ASCO, 2010). Clinical data were extracted from the medical records of patients with PIK3CA mutant tumors. Results: 25 of 1325 (2%, 95% CI 1-3%) patients had a mutation in PIK3CA (11 E545K, 3 E542K, 3 H1047L, 8 H1047R). The patients (64% women) had a median age of 66 (range 34-78). 9 patients (36%, 95% CI 20-56%) were never-smokers. Tumor histologies included: 23 adenocarcinomas, 1 squamous, and 1 large cell neuroendocrine. Stages at presentation were: 10, IV; 2, IIIB; 6, IIIA; 2, IIA; 1, IB; and 4, IA. The median survival of patients with stage IIIB and IV was 21 months. 16 of 25 (64%, 95% CI 44-80%) had co-existing mutations in other oncogenes: 10, KRAS; 1, MEK1; 1, BRAF; 1, EML4-ALK; and 3, EGFR exon 19 deletions. Of the 3 patients with EGFR mutations, only 2 tumors responded to erlotinib, with acquired resistance developing at 5 and 15 months. The tumor with BRAF responded to gefitinib. Stable disease was the response in the patient with EML4-ALK given crizotinib. Conclusions: We found PIK3CA mutations in all histologic types of non-small cell lung cancer. They are not mutually exclusive with mutations in EGFR, KRAS, BRAF, and EML4-ALK. Data on the impact of PIK3CA mutations on the efficacy of targeted therapies (erlotinib, crizotinib) are scant. The testing of agents targeting PIK3CA requires complete genotyping of tumor specimens to assess the potentially confounding role of co-existing mutations to affect responses. Support: NIH T32, P01 CA129243, RC2 CA148394.
IL-10 Differentially Affects IgE and IgG4 Production Through Distinct Mechanisms
Authors: Adora A. Lin, Thomas B. Nutman
Journal: Journal of Allergy and Clinical Immunology (2017)

Control of allergic disease is associated with decreased allergen-specific IgE and increased allergen-specific IgG4. Although IL-10 has been shown to contribute to changes in the IgE/IgG4 balance, the mechanisms underlying these changes are largely unknown. The present study explored how IL-10 differentially regulates human IgE and IgG4 production. PBMCs and highly purified total (CD3-CD19+CD20+), antigen-naïve (CD3-CD19+CD21+CD27-), and antigen-experienced (CD3-CD19+CD21+CD27+) B cells were cultured with combinations of IL-4, IL-10, and anti-CD40. Quantitative PCR was performed for Cε and Cγ4 germline transcripts (GLTs). IgG and IgE isotypes were quantified from culture supernatants using multiplexed immunoassays. In PBMC cultures, IL-4 induced production of both IgE and IgG4 (IgE: mean 16.2-fold above baseline; IgG4: mean 4.7-fold). At the transcriptional level, IL-4 increased expression of Cε and Cγ4 GLTs to 54.1-fold and 5.3-fold above baseline, respectively. Addition of IL-10 significantly (p<0.01) reduced IL-4-induced IgE production to 4.6-fold and expression of Cε GLTs to 24.7-fold above baseline, without affecting IgG4 production or expression of Cγ4 GLTs. In cultures of isolated total B cells and B cell subsets, IL-10 had no significant effect on IL-4-induced IgE production; however, IL-10 markedly increased IL-4-induced IgG4 production over 20-fold. IL-4-induced transcription of Cε and Cγ4 GLTs in isolated B cells was not affected by IL-10. IL-10 acts indirectly through accessory cells present in PBMCs to downregulate IL-4-induced production of IgE. In contrast, IL-10 can act directly on B cells to upregulate IL-4-induced production of IgG4, with its effects on isolated B cells being downstream of germline transcription.
Thyroid lymphoma presenting as a rapidly expanding neck mass.
Authors: J. Naidoo, S. O'Briain, N. Sheehy, E. Vandenberghe, C. Gilham, D. O'Mahony
Journal: Journal of Clinical Oncology (2011)

e18558 Background: Thyroid lymphoma is a rare clinical entity accounting for 0.2% of thyroid cancers in Ireland. It commonly presents with a rapidly enlarging neck mass. The aim of this study was to review our experience of thyroid involvement by lymphoma. Methods: A retrospective review of lymphoma referrals over a 12 year period (1998-2010), identified 12 cases of thyroid involvement. Patient demographics, clinical presentation, investigations, staging, diagnosis, treatment, and outcomes were assessed. Results: Of the 12 patients, 11 were female. The median age was 69 years (range 22-82 years). Forty six percent presented with a symptomatic neck mass. Median duration of symptoms at presentation was 2 months. Thyroid dysfunction was seen in 75% of patients. On histological review, 9 patients had diffuse large B cell lymphoma, 2 had follicular lymphoma, and 1 had Hodgkin's lymphoma. Eight of 12 patients presented with stage I/II disease. Seventy five percent of patients were treated with systemic chemotherapy and 25% received a combination of chemotherapy and radiotherapy. A complete response was seen in 8 (67%) patients and a partial response in 2 (17%) patients. Two patients are currently on treatment. Two (17%) patients underwent emergency surgery. The median overall survival was 37 months (6-149 months). Conclusions: The differential for a rapidly enlarging neck mass includes thyroid lymphoma and anaplastic thyroid cancer, early diagnosis is essential to facilitate appropriate treatment. Successful outcomes may be achieved in patients with thyroid lymphoma.
Association of liposomal pegylated doxorubicine, fludarabine and cyclophosphamide as first line treatment in disseminated small B-cell lymphoma in adult patients
Authors: P.-L. Soubeyran, H. Demeaux, C. Blanc-Bisson, S. Mathoulin-Pelissier, J. Ceccaldi, O. Fitoussi, M. Kind, R. Lupo, V. Picot, B. Hoerni
Journal: Journal of Clinical Oncology (2005)

6622 Background: In a search for the best regimen to treat disseminated small B-cell lymphoma we designed a new schedule based on fludarabine and cyclophosphamide combination with addition of pegylated doxorubicine thus expecting to add efficacy without increasing toxicity. Methods: In a 2-step multicentric phase II trial (Simon design), patients newly diagnosed with small B-cell lymphoma were treated by cyclophosphamide 300 mg/m2/d d1–5, fludarabine 25 mg/m2/d d1–3 and pegylated doxorubicine 30mg/m2 d1 IV every 28 days. Patients received 4 to 6 cycles depending on response after 2 cycles. The primary objective was efficacy (complete response or unconfirmed complete response (CR/ CRu)) at the end of treatment. Results: Among 41 patients (pts) registered, histologies were as follows: follicular - 17 pts, marginal zone -12 pts, lymphocytic - 6 pts, mantle cell - 5 pts, unspecified small B-cell - 1 pt. Median age was 56.1 years (34–70). 83% of the pts presented with stage IV disease. 12 and 5 pts classified in intermediate and high categories of the FLIPI. Among 39 evaluable patients, 22 achieved CR/CRu, 56.4% [39.6–72.2%] for an overall response rate of 94.9%. Among 188 cycles administrated, main toxicities were: febrile neutropenia (11.7%), grade 3–4 leucopenia (59%), anemia (13.9%) and thrombocytopenia (10.7%). Leucopenia persisted after the end of treatment in 8 patients; most resolved within 8 months. Non-hematologic toxicities were alopecia (31.4%), vomiting (30.4%) and mucositis (11.2%). Two opportunistic infections were reported: cryptosporidiosis and pneumocystosis. No cardiac toxicity was observed. 12 patients stopped treatment early because of toxicity. One toxic death secondary to febrile neutropenia occurred. Conclusions: CFC combination shows high CR rate. It compares favorably to other fludarabine-containing regimen and deserves further investigation. However toxicity profile can lead to restrict it only to high risk patients. No significant financial relationships to disclose.