Search

In patients with chronic myeloid leukemia, BCR-ABL mutations contribute to resistance to tyrosine kinase inhibitor therapy. We examined the occurrence of treatment-emergent mutations and their impact on response in patients from the ENESTnd phase 3 trial. At the 3-year data cutoff, mutations were detected in approximately twice as many patients (21) on imatinib 400mg once daily as on nilotinib (11 patients each on nilotinib 300mg twice daily and nilotinib 400 mg twice daily). The majority of mutations occurred in patients with intermediate or high Sokal scores. Most mutations (14 [66.7%]) emerging during imatinib treatment were imatinib-resistant and nilotinib-sensitive. Incidence of the T3151 mutation was low (found in 3, 2, and 3 patients on nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, and imatinib, respectively) and mostly occurred in patients with high Sokal scores. Of the patients with emergent mutations, 1 of 11,2 of 11, and 7 of 21 patients on nilotinib 300mg twice daily, nilotinib 400mg twice daily, and imatinib, respectively, progressed to accelerated phase/blast crisis (AP/BC) on treatment. Overall, nilotinib led to fewer treatment-emergent BCR-ABL mutations than imatinib and reduced rates of progression to AP/BC in patients with these mutations. [ABSTRACT FROM AUTHOR]

Introduction: CD34+ cells collected for autologous bone marrow transplantation (BMT) are usually quantified in the apheresis product after collection, but the necessity to repeat these measures post-thaw is controversial. Methods: We examined the loss of CD34+ cells after collection, preparation for freezing and post-thaw in apheresis products collected for BMT. Results: Median number of CD34+ cells collected per unit was 1.61×106/kg, viability: 97–100%. This number decreased to 1.38×106/kg, viability: 96–100% before freezing and was 1.17×106/kg post-thaw. Viability decreased to 86–98%. The relative loss of viable PBHPC showed an inverse correlation with the ratio “CD34+ cells/total nucleated cells” (r =−0.45; p =<0.0005). This relative loss was largest in patients with Hodgkin’s lymphoma. Conclusion: Cryopreservation and thawing of PBHPCs in leukapheresis products provokes a small but significant stem cell loss. So, quantification of viable CD34+ cells post-thaw is important, especially in poorly mobilizing patients. Besides, the ratio “CD34+ cells/total nucleated cells” after leukapheresis is an important parameter for prediction of neutrophil recovery after BMT. [ABSTRACT FROM AUTHOR]

Background: Nilotinib is a selective, potent BCR-ABL inhibitor. Previous studies demonstrated the efficacy and safety of nilotinib in Philadelphia chromosome-positive chronic myeloid leukemia patients in chronic phase (CML-CP) or accelerated phase who failed prior imatinib.Methods: This expanded access trial further characterized the safety of nilotinib 400 mg twice daily in patients with CML-CP (N = 1422).Results: In this large, heavily pretreated population, nilotinib demonstrated significant efficacy, with complete hematologic response and complete cytogenetic response achieved in 43% and 34% of patients, respectively. Responses were rapid, mostly occurring within 6 months, and were higher in patients with suboptimal response to imatinib, with 75% and 50% achieving major cytogenetic response and complete cytogenetic response, respectively. At 18 months, the progression-free survival rate was 80%. Most patients achieved planned dosing of 400 mg twice daily and maintained the dose >12 months. Nonhematologic adverse events (AEs) were mostly mild to moderate and included rash (28%), headache (25%), and nausea (17%). Grade 3 or 4 thrombocytopenia (22%), neutropenia (14%), and anemia (3%) were low and managed by dose reduction or brief interruption. Grade 3 or 4 elevations in serum bilirubin and lipase occurred in 4% and 7% of patients, respectively. The incidence of newly occurring AEs decreased over time. Of patients who experienced a dose reduction because of AEs and attempted a re-escalation, 87% successfully achieved re-escalation to the full dose.Conclusions: This large study confirms that nilotinib was well tolerated and that grade 3 or 4 AEs occurred infrequently and were manageable through transient dose interruptions. [ABSTRACT FROM AUTHOR]

Background: Treatment recommendations have been developed for management of patients with chronic myeloid leukemia (CML).Methods: A 30-item multiple-choice questionnaire was administered to 435 hematologists and oncohematologists in 16 Latin American countries. Physicians self-reported their diagnostic, therapeutic, and disease management strategies.Results: Imatinib is available as initial therapy to 92% of physicians, and 42% of physicians have access to both second-generation tyrosine kinase inhibitors. Standard-dose imatinib is the preferred initial therapy for most patients, but 20% would manage a young patient initially with an allogeneic stem cell transplant from a sibling donor, and 10% would only offer hydroxyurea to an elderly patient. Seventy-two percent of responders perform routine cytogenetic analysis for monitoring patients on therapy, and 59% routinely use quantitative polymerase chain reaction. For patients who fail imatinib therapy, 61% would increase the dose of imatinib before considering change to a second-generation tyrosine kinase inhibitor, except for patients aged 60 years, for whom a switch to a second-generation tyrosine kinase inhibitor was the preferred choice.Conclusions: The answers to this survey provide insight into the management of patients with CML in Latin America. Some deviations from current recommendations were identified. Understanding the treatment patterns of patients with CML in broad population studies is important to identify needs and improve patient care. [ABSTRACT FROM AUTHOR]

The GSTM1 and GSTT1 genes reduce the effects of exposure to cytotoxic agents. Both genes have a null variant allele in which the entire gene is absent. On the other hand, a common polymorphism of the tumour suppressor P53 gene results in either arginine (A) or proline (P) at amino-acid position 72. The A and P alleles code proteins with distinct functions in apoptosis and DNA repair and have been associated with variable risks for several cancers. However, their roles in multiple myeloma (MM) are still unknown. We tested in study whether the GSTM1, GSTT1 and P53 genotypes altered the risk for MM in Brazilian patients. Genomic DNA from 106 patients and 230 controls were analysed by polymerase chain reaction-based methods for identification of the genotypes. Similar frequencies of the GSTM1, GSTT1 and P53 genotypes were seen in patients and controls. Individuals with the distinct genotypes had similar risks for disease. In contrast, an excess of the GSTM1 null (45.1 vs 17.2%, P = 0.009), the P53 PP+AP (70.4 vs 44.8%, P = 0.041) and the GSTM1 null plus P53 PP+AP (29.6 vs 10.3%, P = 0.004) genotypes were seen in MM patients at stage III compared with those at stages I + II. Our data suggest that the GSTM1, GSTT1 and P53 genotypes do not influence the risk for MM. However, the inherited presence of the variant codon 72 P53 allele, described here for the first time, and the absence of the GSTM1 detoxification pathway, seem to act in disease progression in our country. [ABSTRACT FROM AUTHOR]

The article presents a letter to the editor about polymorphisms of glutathione S-transferase mu1 and theta 1 genes in chronic myeloid leukemia.

Purpose: The aim of this study was to compare [ 18 F]FDG and [ 68 Ga]Ga-PSMA-11 PET/CT image findings in patients with multiple myeloma (MM)., Methods: Twenty consecutive patients with symptomatic biopsy-proven MM were submitted to whole body [ 18 F]FDG and [ 68 Ga]Ga-PSMA-11 PET/CT with a time interval of 1-8 days between procedures. All lesions were counted and had their maximum SUV (SUVmax) measured. Intra-class correlation (ICC) was used to assess the agreement between [ 18 F]FDG and [ 68 Ga]Ga-PSMA-11 PET/CT findings., Results: A total of 266 lesions were detected in 19/20 patients. [ 18 F]FDG detected 223/266 (84%) lesions in 17 patients and [ 68 Ga]Ga-PSMA-11 190/266 (71%) lesions in 19 patients. Both procedures did not identify any active lesion in 1 patient. Forty-three (16%) lesions were detected only by [ 68 Ga]Ga-PSMA-11 and 76 (29%) only by [ 18 F]FDG. Both tracers identified 147 (55%) lesions. Intralesional mismatch of FDG-PSMA uptake was identified in 25 of these 147 lesions, found in 8 different patients. Different lesions with uptake of only [ 18 F]FDG or [ 68 Ga]Ga-PSMA-11 in the same patient were found in 4 patients. The highest SUVmax of [ 18 F]FDG and [ 68 Ga]Ga-PSMA-11 had a median (min-max) SUVmax of 6.5 (2.0-37.8) and 5.5 (1.7-51.3), respectively. [ 18 F]FDG and [ 68 Ga]Ga-PSMA-11 respectively identified 18 and 19 soft tissue lesions. False-positive [ 18 F]FDG findings had minimal or no uptake of [ 68 Ga]Ga-PSMA-11. Good reliability (ICC ≥ 0.75) was found for number of lesions, number of soft tissue lesions and highest SUVmax in each patient., Conclusion: [ 18 F]FDG or [ 68 Ga]Ga-PSMA-11 alone can detect most MM lesions. Almost half of the lesions take up only one of the tracers, reflecting increased glycolysis or angiogenesis in specific lesions, and suggesting their possible complementary role in MM. The marked [ 68 Ga]Ga-PSMA-11 uptake in some cases raises the possibility of a theranostic approach in selected patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To analyze the effects of hospital cardiorespiratory physical therapy protocol on the functional capacity and quality of life of patients submitted to hematopoietic stem cell transplantation (HSCT)., Methods: From January to December 2019, bilateral dynamometry, Manovacuometry and Ventilometry, peak expiratory flow "Peak Flow", 6-min walk test (6MWT), SF-36 Quality of Life Questionnaire and Visual Analog Scale (VAS) were applied in patients who have undergone an allogeneic or autologous hematopoietic stem cell transplantation (HSCT), pre-conditioning (initial evaluation) and pre-discharge (final evaluation). The patients were submitted to an intervention protocol, consisting of aerobic training, muscle strengthening and respiratory muscle training, between the two assessments., Results: 29 patients were enrolled in the study and 24 (83%) completed all procedure. Myeloablative and reduced intensity conditioning were performed in 89.6% and 10.4%, respectively; 17 (58%) patients have undergone an autologous HSCT; 10 (35%) identical related allogeneic HSCT, and 2 (7%) haploidentical allogeneic HSCT. The median number of interventions per patient was 3 (1-9). A decreasing in the right and left dynamometry (p  ≤ 0.0001 and 0.002, respectively) and, also in the distance covered in the 6MWT (p  = 0.004), was observed after HSCT. There was no significant difference in respiratory muscle strength, quality of life and fatigue sensation., Conclusion: Cardiorespiratory rehabilitation can preserve functional capacity and quality of life., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2021 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

The T-cell Lymphoma Project is an international registry prospective study that enrolled patients with newly diagnosed peripheral T-cell and NK-cell lymphomas (PTCL). The main objective was to define the clinical features and outcomes, establishing a robust benchmark for future clinical trials. Seventy-four institutions from 14 countries in North America, South America, Europe, and Asia collected data on patients diagnosed and treated at their respective centers between September 2006 and February 2018. Among 1553 PTCL patients, 131 (8.4% of the total cohort) were confirmed to have anaplastic large cell lymphoma - kinase positive (ALCL, ALK+). The median age of the patients was 39 years (18-84). Sixty-five patients (66%) had advanced-stage disease, although majority (45 patients, 54%) had a low-risk International Prognostic Index (IPI) score (0-1). Of 97 patients treated with chemotherapy, 97% received anthracycline-containing regimens. The overall response rate was 81%, with 69 patients (70%) achieving complete remission. Estimated OS and PFS at 3 years were 77% (95% CI: 54%-99%) and 68% (95% CI: 46%-90%), respectively, and at 5 years were very similar, 77% of OS (95% CI: 62%-92%) and 64% of PFS (95% CI: 34%-94%). Multivariate analysis for PFS showed advanced stage (hazard ratios [HR]: 4.72, 95% CI: 1.43-23.9, p = 0.015), elevated lactate dehidrogenade (LDH) (HR 4.85; 95% CI: 1.73-13.60, p = 0.001), and Eastern Cooperative Oncology Group Performance Status scale (ECOG-PS) ≥2 (HR: 5.25; 95% CI: 1.68-16.4, p = 0.024). For OS, elevated LDH (HR: 3.77; 95% CI: 1.98-14.17, p = 0.014) and ECOG-PS ≥2 (HR: 4.59; 95% CI: 1.46-14.39, p = 0.004) were identified. In summary, although the outcome of ALK+ ALCL is superior to that of other PTCLs, it remains sufficiently favorable, given the young median age of the patients. Our results confirm the usefulness of both IPI and Prognostic Index for T-cell Lymphoma (PIT) in identifying groups of patients with different outcomes. Clinical Trials ID: NCT01142674., (© 2022 John Wiley & Sons Ltd.)

Purpose: Isolated case reports mention the uptake of radiolabeled PSMA in lymphoma. However, it is not clear if the intensity of 68Ga-PSMA expression varies among different histological subtypes or if it correlates with 18F-FDG uptake. This study compared both tracers in patients with diverse lymphoma subtypes., Methods: Ten patients with biopsy-proven-lymphoma underwent 18F-FDG and 68Ga-PSMA-PET/CT (maximum time interval: 6 days). Lymphoma subtypes included Hodgkin's lymphoma (HL, three patients) and aggressive and indolent non-Hodgkin's lymphoma (NHL, seven patients). The intensity of PSMA uptake was classified visually as low, intermediate, or high, using blood pool, liver and parotid gland uptake as references. Maximum standardized-uptake value (SUVmax) of each affected site was measured in both sets of images., Results: FDG detected 59/59 involved sites in 10 patients and PSMA 47/59 sites in nine patients. PSMA uptake was generally low, regardless of the intensity of FDG uptake, but it was classified as intermediate in two patients. The median SUVmax varied from 2.0 (2.0-8.2) to 30.9 for FDG and from 1.7 (1.7-1.7) to 4.4 for PSMA, P < 0.0001. The primary lesion of one patient had a marked intralesional mismatch uptake pattern of the tracers, with areas of higher PSMA expression than FDG uptake, and vice-versa. A brain lesion was more easily identified with PSMA than with FDG images., Conclusion: HL and several NHL subtypes may present PSMA uptake. The intensity of PSMA expression is generally lower than that of FDG uptake and seems to present less variation among the different histological subtypes of lymphomas., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: F-fluorodeoxiglucose (F-FDG)-PET/CT has been widely used to evaluate multiple myeloma. Tc-sestamibi (MIBI) scintigraphy has also been proposed for assessing multiple myeloma, but its use with state-of-the-art single-photon emission computed tomography/computed tomography (SPECT/CT) technology has not been fully evaluated.This study aimed to compare these two imaging modalities in multiple myeloma staging., Materials and Methods: Sixty-two patients with recently diagnosed multiple myeloma were submitted to whole-body F-FDG-PET/CT and whole-body MIBI scans plus SPECT/CT of the chest and abdomen/pelvis. Number of focal lesions, contiguous soft tissue involvement (CSTI), extramedullary lesions (EMLs) and diffuse bone marrow (BM) involvement were recorded., Results: PET/CT was positive in 59 patients (95%) and MIBI SPECT/CT in 58 (93%) (P = 0.69). MIBI detected more diffuse bone marrow involvement than PET/CT (respectively 78 vs. 58% of the patients), while PET/CT demonstrated more focal lesions than MIBI SPECT/CT (81 vs. 54% of the patients) (P = 0.002). PET/CT detected EMLs in four subjects and MIBI in one subject. CSTI was found in 28 (45%) and 23 (37%) patients on PET/CT and MIBI images, respectively (P = 0.36). Three patients with lytic lesions and no FDG uptake were MIBI positive, and two subjects with lytic lesions without MIBI uptake were FDG positive., Conclusion: MIBI SPECT/CT performs similarly to F-FDG-PET/CT in identifying sites of active disease in multiple myeloma staging. MIBI is more efficient than FDG for detecting the diffuse involvement of bone marrow but less efficient for detecting focal lesions. Some patients presented a 'mismatch' pattern of FDG/MIBI uptake.

Background: Extranodal natural killer (NK) T-cell lymphoma (ENKTL) is a unique clinicopathological entity, typically associated with poor survival outcomes. Most published data have come from east Asian study groups, with little information available from international cohorts. The effects of treatment advances on routine clinical practice across continental territories has not been clear. We aimed to improve understanding of the clinical characteristics and outcomes of patients with ENKTL., Methods: We did a substudy of patients with ENKTL from the T-cell Project, a global prospective cohort study. The T-cell Project registered consecutively diagnosed adults (>18 years) with newly diagnosed, untreated mature T-cell or NK lymphomas (WHO 2001 or 2008 classifications) from 74 centres in 13 countries (in Asia, Europe, North America, and South America). In total, 1695 patients with mature T-cell or NK lymphomas were enrolled between Oct 12, 2006 and Feb 28, 2018 in the T-cell Project. The first patient with ENKTL was enrolled on Feb 15, 2007, and the last on May 26, 2017. Data on baseline characteristics, first-line treatment, treatment response, and survival outcomes were recorded in a central database (locked March 30, 2019). The primary outcome was 5-year overall survival. The T-cell Project is registered on ClinicalTrials.gov, NCT01142674., Findings: 166 patients were diagnosed with ENKTL, comprising 11% of 1553 eligible registered cases and distributed across 40 participating centres in four continents. At a median follow-up of 44 months (IQR 20-61), overall survival at 5 years was 54% (95% CI 44-63) in patients with nasal disease (n=98) and 34% (27-46) in patients with extranasal disease (n=68)., Interpretation: To our knowledge, this study presents the largest international cohort of patients with ENKTL. We describe a clinically significant improvement in the survival of patients with ENKTL treated in routine clinical practice over the past decade, likely to be attributable to the increasing use of treatment protocols specific for ENKTL., Funding: The Fondazione Cassa di Risparmio di Modena, the Associazione Angela Serra per la Ricerca sul Cancro, the Fondazione Italiana Linfomi, Allos Therapeutics, Spectrum Pharmaceuticals, Associazione Italiana per la Ricerca sul Cancro, and the National Cancer Institute at the National Institutes of Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib., Methods: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing., Results: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months., Conclusions: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary.

Purpose: The purpose was to investigate the presence of hypercoagulability in the very early phase of the host response to an infection in the clinical course of sepsis and septic shock., Material and Methods: Twenty-four patients with chemotherapy-associated febrile neutropenia were evaluated at baseline, at the time of fever onset, and 48 hours thereafter using the thrombin generation test, a more physiological and global assay of hemostasis., Results: The rate of thrombin generation was decreased and no signals of systemic hypercoagulability could be observed during the first 48 hours of sepsis. Moreover, patients that evolved to septic shock presented a more significant impairment in thrombin generation than those with noncomplicated sepsis., Conclusions: Patients with sepsis and febrile neutropenia present an impairment in thrombin generation from very early stages of their disease course. These results suggest that the procoagulant in vitro alterations described during sepsis do not necessarily translate into a clinically relevant systemic hypercoagulable state. These findings could help explain why treatment with systemic anticoagulants did not translate to clinical benefits in human sepsis and highlight the need for a better understanding of the hemostatic alterations in sepsis before new treatments targeting coagulation activation are developed., (© 2013.)

Introduction: CD34(+) cells collected for autologous bone marrow transplantation (BMT) are usually quantified in the apheresis product after collection, but the necessity to repeat these measures post-thaw is controversial., Methods: We examined the loss of CD34(+) cells after collection, preparation for freezing and post-thaw in apheresis products collected for BMT., Results: Median number of CD34(+) cells collected per unit was 1.61×10(6)/kg, viability: 97-100%. This number decreased to 1.38×10(6)/kg, viability: 96-100% before freezing and was 1.17×10(6)/kg post-thaw. Viability decreased to 86-98%. The relative loss of viable PBHPC showed an inverse correlation with the ratio "CD34(+) cells/total nucleated cells" (r=-0.45; p=<0.0005). This relative loss was largest in patients with Hodgkin's lymphoma., Conclusion: Cryopreservation and thawing of PBHPCs in leukapheresis products provokes a small but significant stem cell loss. So, quantification of viable CD34(+) cells post-thaw is important, especially in poorly mobilizing patients. Besides, the ratio "CD34(+) cells/total nucleated cells" after leukapheresis is an important parameter for prediction of neutrophil recovery after BMT., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: In the era of eculizumab, identifying patients with paroxysmal nocturnal hemoglobinuria who may benefit from allogeneic stem cell transplantation is challenging., Design and Methods: We describe the characteristics and overall survival of 211 patients transplanted for paroxysmal nocturnal hemoglobinuria in 83 EBMT centers from 1978 to 2007. Next, we conducted a comparison with a cohort of 402 non-transplanted patients with paroxysmal nocturnal hemoglobinuria diagnosed between 1950 and 2005 in 92 French centers. We compared the occurrence of complications (i.e. thromboembolism and aplastic anemia) using either an individual or a stratum-matching procedure., Results: After a median follow-up of 5 years, the 5-year overall survival rate ± standard error (%) was 68 ± 3 in the transplanted group (54 ± 7 in the case of thromboembolism, 69 ± 5 in the case of aplastic anemia without thromboembolism and 86 ± 6 in the case of recurrent hemolytic anemia without thromboembolism or aplastic anemia). Only thromboembolism as the indication for transplantation was associated with worse outcome (P=0.03). We identified 24 pairs of transplanted and non-transplanted patients with thromboembolism for the matched comparison, with worse overall survival for the transplanted patients (hazard ratio=10.0; 95% confidence interval, 1.3-78.1; P=0.007). This was confirmed by the global matching procedure (P=0.03). As regards aplastic anemia without thromboembolism, 30 pairs were identified for the matched comparison. It was not observed that transplanted patients had a significantly worse overall survival (hazard ratio=4.0; 95% confidence interval, 0.9-18.9; P=0.06). A global matching procedure was not feasible., Conclusions: Allogeneic stem cell transplantation is probably not a suitable treatment option for life-threatening thromboembolism in paroxysmal nocturnal hemoglobinuria.

Despite the good response of stem cell transplant (SCT) in the treatment of multiple myeloma (MM), most patients relapse or do not achieve complete remission, suggesting that additional treatment is needed. We assessed the impact of thalidomide in maintenance after SCT in untreated patients with MM. A hundred and eight patients (<70 years old) were randomized to receive maintenance with dexamethasone (arm A; n = 52) or dexamethasone with thalidomide (arm B; n = 56; 200 mg daily) for 12 months or until disease progression. After a median follow-up of 27 months, an intention to treat analysis showed a 2-year progression-free survival (PFS) of 30% in arm A (95% CI 22-38) and 64% in arm B (95% CI 57-71; P = 0.002), with median PFS of 19 months and 36 months, respectively. In patients who did not achieve at least a very good partial response, the PFS at 2 years was significantly higher when in use of thalidomide (19 vs. 59%; P = 0.002). Overall survival at 2 years was not significantly improved (70 vs. 85% in arm A and arm B, respectively; P = 0.27). The addition of thalidomide to dexamethasone as maintenance improved the PFS mainly in patients who did not respond to treatment after SCT., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: We evaluate the effectiveness and toxicity of high-dose sequential chemotherapy (HDS) as salvage therapy in patients with advanced-stage Hodgkin lymphoma., Patients and Methods: We performed a retrospective analysis on 77 patients receiving HDS between 1998 and 2006. Patients enrolled were in disease progression or relapsed disease, or did not achieve a complete remission after first-line treatment. HDS consisted of the sequential administration of cyclophosphamide and granulocyte colony-stimulating factor with stem cell harvesting, followed by methotrexate plus vincristine and etoposide., Results: The majority of patients had stage III/IV (64%) and B symptoms (71.4%). Disease status improvement after HDS was observed in 24 of 57 patients (42%) previously in disease progression or relapse. HDS-related deaths occurred in 8 of 77 patients (10.4%). Four patients (5.2%) developed acute myeloid leukemia/myelodysplastic syndrome. Overall, disease-free and progression-free survival was 27%, 57%, and 25%, respectively., Conclusion: Despite the treatment-related mortality, HDS is feasible, with satisfactory response rates, even in patients with poor prognosis.

Point mutations within the ABL kinase domain are the most frequent mechanism for reactivation of kinase activity of the BCR-ABL gene and have been associated with clinical resistance to tyrosine kinase (TK) inhibitors in patients with CML, conferring a poor prognosis. T315I (Treonine-->Isoleucine) is a mutation in the exon 6 of BCR-ABL gene that makes the protein resistant to kinase inhibitors currently used for treating CML. Denaturing High-performance liquid chromatography (D-HPLC) allows for high throughput mutation screening. In this study, we screened mutations in exon 6 of the BCR-ABL gene in patients presenting failure or sub optimal response according to Leukemia Net criteria and correlated the presence of mutations with clinical outcome. Genomic DNA was extracted from peripheral blood samples from 93 patients with CML (5 intolerant and 88 resistant). The PCR product was analysed by D-HPLC, and the patients samples with abnormal D-HLPC profiles were submitted to automated sequencing, using specific primers. Overall survival (OS) was calculated from the date of mutation analysis, for the whole group and for both groups (mutation versus no mutation). We screened mutations in exon 6 of the BCR-ABL gene in 93 CML TKI - resistant patients. Twenty-three out of 93 samples (25%) showed an abnormal elution profile. Automated sequencing confirmed the presence of a nucleotide change in 19 out of 23 cases: one polymorphism, T315T, seven known point mutations: T315I, F317L, V339L, M351T, E355G and F359V and three novel mutations: C305R, D325D and I360S. OS for the whole group was 80% in a median observation time of 30 months. OS for patients without the mutation was 87% and with the mutation was 56%, in a median observation time of 37 and 10 months, respectively (p < 0.0001, RR = 68). D-HPLC is a practical and sensitive method for routine clinical monitoring for emergence of kinase domain mutations and may be useful for optimising therapy in CML. The screening of mutations in exon 6 is clinically relevant, once the presence of mutations confers a poor outcome. Early detection of emerging mutant clones may help in decision-making for alternative treatment.