Role of up-front autologous stem-cell transplantation in peripheral T-cell lymphoma for patients in response after induction: an analysis of patients from LYSA centers.

Background: Peripheral T-cell lymphoma (PTCL) remains a therapeutic challenge. Due to the rarity and the heterogeneity of PTCL, no consensus has been achieved regarding even the type of first-line treatment. The benefit of autologous stem-cell transplantation (ASCT) is, therefore, still intensely debated. Patients and methods: In the absence of randomized trials addressing the role of ASCT, we performed a large multicentric retrospective study and used both a multivariate proportional hazard model and a propensity score matching approach to correct for sample selection bias between patients allocated or not to ASCT in intention-to-treat (ITT). Results: Among 527 patients screened from 14 centers in France, Belgium and Portugal, a final cohort of 269 patients ≤65 years old with PTCL-not otherwise specified (NOS) (N = 78, 29%), angioimmunoblastic T-cell lymphoma (AITL) (N = 123, 46%) and anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK-ALCL) (N = 68, 25%) with partial (N = 52, 19%) or complete responses (N = 217, 81%) after induction was identified and information about treatment allocation was carefully collected before therapy initiation from medical records. One hundred and thirty-four patients were allocated to ASCT in ITT and 135 were not. Neither the Cox multivariate model (HR = 1.02; 95% CI: 0.69-1.50 for PFS and HR = 1.08; 95% CI: 0.68-1.69 for OS) nor the propensity score analysis after stringent matching for potential confounding factors (logrank P = 0.90 and 0.66 for PFS and OS, respectively) found a survival advantage in favor of ASCT as a consolidation procedure for patients in response after induction. Subgroup analyses did not reveal any further difference for patients according to response status, stage disease or risk category. Conclusions: The present data do not support the use of ASCT for up-front consolidation for all patients with PTCL-NOS, AITL, or ALK-ALCL with partial or complete response after induction.

Mast cells' involvement in inflammation pathways linked to depression: evidence in mastocytosis.

Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation-induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells' potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were enrolled in the study and compared healthy age-matched controls. Depression and stress were evaluated with the Beck Depression Inventory revised and the Perceived Stress Scale. All patients had measurements of TRP, serotonin (5-HT), kynurenine (KYN), indoleamine 2,3-dioxygenase 1 (IDO1) activity (ratio KYN/TRP), kynurenic acid (KA) and quinolinic acid (QA). Patients displayed significantly lower levels of TRP and 5-HT without hypoalbuminemia or malabsorption, higher IDO1 activity, and higher levels of KA and QA, with an imbalance towards the latter. High perceived stress and high depression scores were associated with low TRP and high IDO1 activity. In conclusion, TRP metabolism is altered in mastocytosis and correlates with perceived stress and depression, demonstrating mast cells' involvement in inflammation pathways linked to depression.

Decreased tryptophan and increased kynurenine levels in mastocytosis associated with digestive symptoms.

The main metabolism pathway of tryptophan is protein formation, but it can also be metabolized into serotonin and kynurenine. Indoleamine 2,3-dioxygenase (IDO) is the enzyme that catalyzes the degradation of tryptophan into kynurenine. Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in various tissues with 57% of patients having gastrointestinal involvement. We studied tryptophan metabolism in mastocytosis patients displaying or not gastrointestinal features and healthy subjects (n = 26 in each group). Mastocytosis patients with digestive symptoms displayed significantly increased kynurenine level and IDO activity as compared to healthy controls and mastocytosis patients without digestive symptoms. This could be linked to mast cell-mediated digestive inflammation among patients with mastocytosis. This work is the first focusing on kynurenine pathway in a mast cell disease and could help to understand the pathogenesis of digestive features in mastocytosis as well as in other mast cell-mediated diseases.

FDG-PET/CT findings in systemic mastocytosis: a French multicentre study.

INTRODUCTION: Mastocytosis is a clonal haematological disease characterized by uncontrolled proliferation and the activation of mast cells. The value of FDG-PET/CT (FDG-PET) in mastocytosis has yet to be determined. METHODS: We retrospectively identified patients with an established diagnosis of systemic mastocytosis (SM), according to the WHO criteria, who underwent PET using the French Reference Centre for Mastocytosis database. Semi-quantitative and visual analysis of FDG-PET was performed and compared to the clinico-biological data. RESULTS: Our cohort included 19 adult patients, median age 65 years [range 58-74], including three with smouldering SM (SSM), three with aggressive SM (ASM), 10 with an associated clonal haematological non-mast-cell lineage disease (SM-AHNMD), and three with mast cell sarcoma (MCS). FDG-PET was performed at the time of the SM diagnosis (15/19), to evaluate lymph node (LN) activity (3/19) or the efficacy of therapy (1/19). FDG uptake was observed in the bone marrow (BM) (9/19, 47%), LN (6/19, 32%), spleen (12/19, 63%), or liver (1/19, 5%). No significant FDG uptake was observed in the SSM and ASM patients. A pathological FDG uptake was observed in the BM of 6/10 patients with SM-AHNMD, appearing as diffuse and homogeneous, and in the LN of 5/10 patients. All 3 MCS patients showed intense and multifocal BM pathological uptake, mimicking metastasis. No correlation was found between the FDG-PET findings and serum tryptase levels, BM mast cell infiltration percentage, and CD30 and CD2 expression by mast cells. CONCLUSIONS: FDG uptake does not appear to be a sensitive marker of mast cell activation or proliferation because no significant FDG uptake was observed in most common forms of mastocytosis (notably purely aggressive SM). However, pathological FDG uptake was observed in the SM-AHNMD and in MCS cases, suggesting a role of FDG-PET in their early identification and as a tool of therapeutic assessment in this subgroup of patients.

Paediatric mastocytosis: a systematic review of 1747 cases.

Paediatric mastocytosis was previously considered to be a benign and spontaneously regressing disease. However, this evolution is impossible to predict. To clarify the characteristics and course of paediatric mastocytosis, we performed a literature review of 1747 cases published between 1950 and April 2014. Lesions occurred before the age of 2 years in 90% of cases, and presented as urticaria pigmentosa (75% of cases), mastocytoma (20%) or diffuse cutaneous mastocytosis (5%). The male-to-female ratio was 1·4. KIT D816V mutation was detected in 34% of 215 tested patients. Clinical regression (complete or partial) occurred in 67% of cases and stabilization in 27%. However, the outcome was fatal in 2·9% of patients.

Efficacy of anakinra for various types of crystal-induced arthritis in complex hospitalized patients: a case series and review of the literature.

BACKGROUND: There are few data on anakinra use after failure of conventional medications for crystal-induced peripheral arthritis and/or crowned dens syndrome among complex hospitalized patients. METHODS: We retrospectively analyzed the outcome of six patients affected with subacute crystal-induced arthritis who had received anakinra in second or third line therapy, including three patients with crowned dens syndrome and three others with gouty arthritis. Patients' comorbidities, reasons for anakinra use and associated drugs, and outcomes were recorded. RESULTS: All patients presented with elevated inflammatory syndrome, systemic symptoms with poly/oligoarthritis. Except for absolute contraindications, all patients were previously treated with full or decreased dose of NSAID, colchicine, and/or glucocorticoids, with unsatisfactory response. All three gouty patients exhibited complete responses in all acute involvements under anakinra within 3 to 5 days, including one of them who needed the reintroduction of colchicine treatment that was previously unsuccessful. Crowned dens syndrome patients, including two with pseudogout and one with subacute hydroxyapatite deposition disease, needed 9 to 11 days to achieve complete response. Tolerance to anakinra was good. CONCLUSION: In case series of complex hospitalized patients, anakinra showed good activity in crowned dens syndrome and associated crystal-induced peripheral arthritis, with longer treatment duration than in gouty arthritis.

Alterations in bone mineral density and bone turnover markers in newly diagnosed adults with lymphoma receiving chemotherapy: a 1-year prospective pilot study.

BACKGROUND: Bone mineral density (BMD) loss is poorly defined in lymphoma patients. The aim of this study was to measure the extent of BMD loss in newly diagnosed lymphoma patients receiving chemotherapy. PATIENTS AND METHODS: This was a prospective, single-center study conducted in patients aged≥18 years with previously confirmed lymphoma treated by chemotherapy. Patients with low baseline BMD defined as Z/T-score less than or equal to -2.5 and/or history of osteoporotic fractures were excluded. BMD was measured at baseline before initiating chemotherapy and 1 year later. Predictive factors of BMD loss were investigated. RESULTS: Forty-one lymphoma patients (31 males and 10 females) receiving chemotherapy were enrolled. The median age at diagnosis was 59 (range: 19-86) years. Histological subtypes were predominantly diffuse large B-cell lymphoma (58%), mostly stage III-IV (54%). All patients received chemotherapy and 22% of patients received second-line treatment due to relapse or progressive disease. Thirty-two patients were evaluable at 1 year. The mean BMD changes were: -2.7%±3.9% for lumbar spine (P<0.001), -2.2%±7.6% for femoral neck (P<0.01) and -2.6%±4.5% for total hip (P<0.0001). In multivariate analysis, predictive factors of BMD loss at baseline were (i) at lumbar spine: female gender (P=0.01), higher lactate dehydrogenase level (P=0.04) and lower creatinine clearance (P=0.01); (ii) at total hip: lower albumin (P=0.01), higher corrected serum calcium (P<0.01), lower alkaline phosphatase (AP) (P<0.01) and autologous stem cell transplant (P=0.03); and (iii) at femoral neck: higher corrected serum calcium (P=0.02) and lower bone AP (P=0.01). CONCLUSION: Adult patients with known lymphoma receiving chemotherapy experienced significant BMD loss at 1 year.

Lymphoma occurring in patients over 90 years of age: characteristics, outcomes, and prognostic factors. A retrospective analysis of 234 cases from the LYSA.

BACKGROUND: Lymphoma occurring in patients aged 90 or older is not uncommon, and its incidence is expected to increase over time. Management of these patients is difficult given their underlying fragility and the lack of information regarding this population. PATIENTS AND METHODS: We retrospectively analyzed 234 patients diagnosed with lymphoma at the age of 90 years or older (90+) between 1990 and 2012 to describe their characteristics, management, outcomes and prognostic factors. RESULTS: The median age was 92 years; 88% were B-cell lymphomas consisting mainly in diffuse large B-cell lymphoma. The median overall survival (OS) was 7.2 months (range, 0-92 months) for the 227 patients with non-Hodgkin Lymphoma (NHL), with a significant difference between aggressive and indolent NHL (5.2 months versus 19.4 months, respectively). We further analyzed 166 NHL patients for whom detailed characteristics were available. Among these patients, 63.5% received a treatment, either local (7.5%) or systemic (56%). Lymphoma was reported as the main cause of death (40%). Treatment administration was associated with improved OS in patients with aggressive (P < 0.001) but not indolent NHL (P = 0.96). In patients with aggressive NHL, hypoalbuminemia appeared as a strong and independent negative prognostic factor. CONCLUSIONS: The median OS is short in 90+ patients diagnosed with lymphoma but some patients experience prolonged survival. Lymphoma represents the main cause of death in these patients. Treatment may improve survival of selected patients with aggressive but not indolent NHL. Management of these patients may be guided by prognostic factors identified in this study, notably serum albumin.

High response rate and improved exercise capacity and quality of life with a new regimen of darbepoetin alfa with or without filgrastim in lower-risk myelodysplastic syndromes: a phase II study by the GFM.

Darbepoetin (DAR), with or without granulocyte colony-stimulating factor (G-CSF), has proved effective in treating anemia in patients with lower-risk myelodysplastic syndrome (MDS), but its effects on quality of life (QoL) and exercise functioning are less well established. In this phase II study (no. NCT00443339), lower-risk MDS patients with anemia and endogenous erythropoietin (EPO) level <500 IU/L received DAR 500 µg once every 2 weeks for 12 weeks, with G-CSF added at week 12 in non-responders. Physical performance was assessed with the 6-min walking test and, for fit patients, maximal oxygen consumption (VO2max). QoL was evaluated using SF-36 and FACT-An tests. In 99 patients, erythroid response rate according to IWG 2006 criteria was 48 and 56 % at 12 and 24 weeks, respectively. Addition of G-CSF rescued 22 % of non-responders. In 48 % of the responders, interval between darbepoetin injections could be increased for maintenance treatment. Serum EPO level was the only independent predictive factor of response at 12 weeks, and its most discriminant cutoff value was 100 IU/L. QoL and VO2max showed improvement over time in responders, compared with non-responders. With a median follow-up of 52 months, median response duration was not reached, and 3-year cumulative incidence of acute myeloid leukemia and overall survival (OS) was 14.5 and 70 %, respectively. Baseline transfusion dependence, International Prognostic Score System (IPSS), and Revised IPSS accurately predicted OS from treatment onset. Tolerance of darbepoetin was good. In conclusion, this regimen of darbepoetin every 2 weeks yielded high response rates and prolonged response duration. Objective improvement in exercise testing and in patient-reported QoL confirms the clinical relevance of anemia correction with erythropoiesis-stimulating agents.

Role of social status and social environment on net survival in patients with chronic lymphocytic leukemia: A high-resolution population-based study.

BACKGROUND: The prognostic roles of social status and social environment in chronic lymphocytic leukemia have been highlighted in some solid tumors but remain unclear in hematological malignancies. The objective of this study was to evaluate the influence of individual social status (with socioprofessional category, SPC) and social environment (with European deprivation index, EDI) on net survival in a high-resolution population with CLL. METHODS: We included CLL patients from the Regional Register of Hematological Malignancies in Normandy belonging to the French Network of Cancer Registries (Francim). The SPC variable was divided into 5 categories: farmers, craftsmen, higher employment, intermediate employment, and workers/employees. Net survival was used to estimate the excess of mortality in CLL independent of other possible causes of death using French life tables. Net survival was estimated with a nonparametric method (Pohar-Perme) and with a flexible excess mortality hazard model. Missing data were handled with multiple imputation. RESULTS: A total of 780 patients were included. The median follow-up was 7.9 years. The crude survival at 10 years was 50%, and the net survival at 10 years was 80%. In multivariate analysis, a higher age (EHR: 1.04 [1.01-1.07]), being a craftsman (EHRcraftsmen/higher.employment: 4.15 [0.86-20.15]), being a worker or an employee (EHRworkers.employees/higher.employment: 3.57 [1.19-10.7]), having a Binet staging of B or C (EHR: 3.43 [1.84-6.42]) and having a lymphocyte count > 15 G/L (EHR: 3.80 [2.17-6.65]) were statistically associated with a higher risk of excess mortality. EDI was not associated with excess mortality (EHR: 0.97 [0.90-1.04]). CONCLUSION: Socioprofessional category was a prognostic factor for an excess of mortality in CLL. Craftsmen and workers/employees shared a worse prognosis than workers with higher employment. The social environment was not a prognostic factor. Further work should be performed to explore causal epidemiologic or biological factors and other hematological malignancies.

[Eosinophilic dermatosis associated with hematological disorders: A clinical, histopathological and immunohistochemical study of six observations]. / Dermatose éosinophilique associée aux hémopathies : étude clinique, histopathologique et immunohistochimique de six cas.

BACKGROUND: Eosinophilic dermatosis of hematologic disease (EDH) or insect bite-like reaction is a pruritic dermatitis described mostly in patients with chronic lymphocytic leukaemia (CLL). We describe six patients with the disorder in association with CLL and other blood dyscrasias. PATIENTS AND METHODS: We reviewed the medical records of patients with EDH seen between 2004 and 2009 in our department and re-examined histological slides. RESULTS: Mean age at dermatosis onset was 75.6 years and the sex ratio was 1. There were three CLL, two mantle-cell lymphomas and one MALT-type lymphoma. The dermatitis was quite polymorphic, with erythematous papules, wheals and plaques. The initial skin lesions appeared at the same time as or after the diagnosis of haematological neoplasm. Their reappearance heralded relapse of the blood disease in three cases. Histologically, all lesions had a dense dermal infiltrate of small, mostly CD4+ T-cells, with numerous eosinophils. In three patients, there was marked folliculotropism, resembling folliculotropic T-cell lymphoma. In most cases, EDH disappeared after appropriate chemotherapy for the blood disorder. DISCUSSION: Our cases show that the clinical expression of EDH is quite polymorphic. Its appearance may precede relapse of or may indicate prompt search screening for blood dyscrasia. The most efficient treatment of this dermatosis appears to be specific chemotherapy for the blood dyscrasia. There is reason to believe that a population of T-helper 2 (Th2) lymphocytes, reactive to malignant B-cells, induces tissue eosinophilia, mainly through production of interleukin (IL)-5, among other cytokines. Eosinophils appear to be the main effector cells.

Drug rash with eosinophilia and systemic symptoms after chlorambucil treatment in chronic lymphocytic leukaemia.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous drug reaction with a long duration of eruption and serious organ involvement. The mortality rate has been estimated at about 10%. Aromatic anticonvulsants, sulphamides, minocycline and more rarely carbamazepine are the principal responsible drugs. We report the first case of chlorambucil-induced DRESS syndrome in a 70-year-old man recently diagnosed with chronic lymphocytic leukaemia. He developed recurrent skin rash, fever, hypereosinophilia, and acute renal failure after rechallenge with chlorambucil. The condition improved slowly after stopping medication and systemic steroids. Prompt recognition of a chlorambucil drug reaction is essential in patients receiving chemotherapy.

Tyrosine kinase inhibitors and solid tumours: case report and review of the literature.

Bcr-Abl tyrosine kinase inhibitors (TKIs) such as imatinib or dasatinib produce high cytogenetic response rates in patients with Philadelphia-positive chronic myeloid leukaemia (CML) with a good overall safety profile. Despite a complete molecular response, it is currently recommended to continue these targeted therapies to avoid relapse. The immediate and short-term TKI side effects are well known, but the long-term side effects have not yet been clearly identified. A preclinical study in rats treated with TKI showed a statistically significant increase in benign and malignant renal tumours. The authors report the case of a 61-year-old man with CML treated with imatinib with a good response, and they switched to dasatinib after grade 4 hepatic toxicity. He had received treatment with 400 mg of imatinib per day for 77 days, followed by dasatinib for 133 days. He developed a metastatic carcinoma of unknown origin during TKI therapy. Despite chemotherapy, the patient died 2 months after the diagnosis. Although several cases of solid tumours have been reported during TKI therapy, the link between cancer and TKIs is not yet clear. Imatinib has remarkably improved the prognosis of patients with CML. Monitoring of the long-term safety profile of TKIs is essential due to the prolonged survival of these patients.

[Bortezomib-induced eruption: Sweet syndrome? Two case reports]. / Toxidermie au bortézomib : syndrome de Sweet? Deux cas.

BACKGROUND: Bortezomib (Velcade) is a proteasome inhibitor used in the treatment of myeloma and other blood dyscrasias. We report the cases of two patients who developed a peculiar toxic rash suggestive of Sweet's syndrome while receiving bortezomib; one patient also presented giant mucous membrane ulcerations. PATIENTS AND METHODS: Case 1: bortezomib treatment was started in a 62-year-old man for mantle cell lymphoma. Ten days after the first treatment cycle, giant, painful oral ulcerations were noted but they resolved spontaneously. One week after the second cycle, further oral ulceration appeared, this time with a papulonodular skin rash. Histology showed neutrophilic dermal infiltrates in the skin with predominantly lymphocytic inflammation of the oral mucosa. Bortezomib was stopped and all lesions resolved with colchicine treatment. Case 2: a 46-year-old woman was receiving bortezomib treatment for plasma cell leukemia. A febrile skin rash appeared two days after the first treatment cycle but resolved spontaneously. After the first bortezomib injection during the next cycle, painful papules and nodules appeared on the trunk. The skin biopsy results were consistent with Sweet's syndrome. The lesions disappeared spontaneously. Dexamethasone was administered concomitantly with bortezomib in the ensuing cycles and there was no relapse of the skin lesions. DISCUSSION: Bortezomib-induced skin lesions are common and usually do not justify treatment withdrawal. Published observations of bortezomib-induced eruption occasionally show clinical and histological features of Sweet's syndrome, but there has been no mention of oral mucosal ulcerations. In our cases, these could be related to bortezomib-induced neutrophilic dermatosis.

Low dose Rituximab for pre-emptive treatment of Epstein Barr virus reactivation after allogenic hematopoietic stem cell transplantation.

INTRODUCTION: The most used preemptive therapy for Epstein Barr virus reactivation post allogeneic hematopoietic stem cell (HSCT) transplant is Rituximab, 375 mg/m2, once weekly until EBV viremia negativity. There is no data suggesting such a high dose. OBJECTIVE: We hypothesized that a lower dose of Rituximab would be as efficient with less toxicity. PATIENTS: In a retrospective, monocentric study, we analyzed 16 consecutive patients treated preemptively with low dose Rituximab for EBV reactivation post HSCT. Patients were treated with low Rituximab dose of 100 mg/m² weekly. Success was defined by a decrease of EBV viremia of 1 log10 and below 1000 UI/ml, and the absence of post-transplant lymphoproliferative disorder (PTLD). RESULTS: Success rate was 93.4% (15/16). One (1/16, 6%) PTLD was diagnosed after preemptive therapy, despite a negative viremia. CONCLUSION: A low dose of Rituximab of 100 mg/m² per injection for pre-emptive therapy of EBV reactivation post HSCT is safe and effective for preventing PTLD. Prospective, randomized, multicentric trials with larger number of patient are needed to determine the best rituximab dose.

Pulmonary hypertension associated with myeloproliferative disorders: a retrospective study of ten cases.

BACKGROUND: Pulmonary hypertension (PH) is a severe hemodynamic disorder in which the pulmonary artery pressure is persistently elevated, leading to right-sided heart failure. Some studies have suggested an association between PH and myeloproliferative diseases (MPD). OBJECTIVES: This study describes clinical, hematological and hemodynamic characteristics of PH associated with MPD. METHODS: We retrospectively reviewed 10 cases of PH associated with MPD: polycythemia vera (8 patients) and essential thrombocythemia (2 patients), followed between 1993 and 2002. The baseline evaluation was established by right-sided heart catheterization, ventilation/perfusion lung scan and pulmonary angiography if required. RESULTS: Six patients had confirmed chronic thromboembolic pulmonary hypertension (CTEPH) and 4 had pulmonary arterial hypertension (PAH) associated with MPD without other risk factors for PAH. The hemodynamic characteristics of CTEPH and PAH associated with MPD were similar. The diagnosis of CTEPH was concomitant to that of MPD in all cases (5 polycythemia vera and 1 essential thrombocythemia). The PAH associated with MPD occurred later in the evolution of the MPD (3 polycythemia vera and 1 essential thrombocythemia) with a median of 162 months after the diagnosis of MPD, and it was associated with myeloid metaplasia (p < 0.01). CONCLUSION: We describe 2 distinct forms of PH in the context of MPD: CTEPH, which is diagnosed at an early stage of the MPD, and PAH, which occurs later in the course of the MPD and is associated with myeloid metaplasia. Progressively increasing dyspnea in a patient with an MPD warrants further investigation to rule out PAH and CTEPH, while a diagnosis of CTEPH warrants ruling out MPD.

[Haematopoietic stem cell transplantation in the treatment of autoimmune diseases]. / Intensification thérapeutique dans les maladies auto-immunes.

PURPOSE: During the past ten years, more than 1000 patients suffering from severe autoimmune disease have received an autologous haematopoietic stem cell transplant. These new therapeutic have been used in systemic sclerosis (scleroderma), multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis and systemic lupus erythematosus. CURRENT KNOWLEDGE AND KEY POINTS: Autologous haematopoietic stem cell transplantation has become a curative option for condition with very poor prognosis as severe systemic sclerosis, lupus erythematosus or other systemic diseases. This review summarizes the current experience in the phase I and II clinical trials in Europe and North America. We describe the main results and the limits of stem cell transplantation in systemic diseases. FUTURE PROSPECTS AND PROJECTS: Autologous haematopoietic stem cell transplant in the treatment of autoimmune disease has evolved from a experimental concept to a clinically feasible and powerful therapy for selected patients with severe disease.

Prediction of relapse by day 100 BCR-ABL quantification after allogeneic stem cell transplantation for chronic myeloid leukemia.

Chronic myeloid leukemia (CML) relapse after allogeneic stem cell transplantation (SCT) is a relatively frequent situation, which is correlated to disease status, time from diagnosis to transplant and T-cell depletion. We evaluated the potential for early minimal residual disease (MRD) BCR-ABL quantification to predict relapse of CML patients receiving allogeneic SCT. Minimal residual disease was analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) at day 100 (d100) in 38 patients with >1 year follow-up after conventional non-T-cell-depleted SCT. Normal ABL control values from 1724 follow-up blood samples were used to define an RQ-PCR amplifiability index and the limits of reliable use of BCR-ABL ratios. We then compared the 14 patients with a high-level d100 BCR-ABL/ABL ratio (> or = 10(-4)) to that of the 24 patients with a negative/low-level ratio (<10(-4)). Despite being comparable for all classical parameters, the incidence of relapse was significantly higher in the high MRD group (11/14 (79%)) compared to that of the low/negative MRD group (7/24 (29%)) (P = 0.009), with d100 MRD values representing an independent risk factor of relapse and disease-free survival, but not of overall survival, in multivariate analysis. These data should facilitate risk-adapted post-transplant immunosuppression and/or tyrosine kinase inhibitor therapy based on an early evaluation of MRD.

Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: a review.

High-dose chemotherapy preceding autologous hematopoietic stem cell transplantation (auto-HSCT) is one treatment option for patients with Hodgkin (HL) or non-Hodgkin lymphoma (NHL). The most frequently used intensive chemotherapy is a combination of carmustine (BCNU), etoposide, cytarabine and melphalan (BEAM). However, BCNU is consistently in short supply, and there has been a recent dramatic increase in its cost, necessitating the utilization of conditioning alternatives. The busulfan-based conditioning regimen known as the busulfan-cyclophosphamide-etoposide (BuCyE) combination is the second most-studied conditioning regimen worldwide after BEAM, and it exhibits a benefit/risk ratio that is comparable to that of BEAM. In addition to these two combinations, the present manuscript also summarizes data reported for other conditioning combinations. Owing to the lack of prospective and comparative studies, a comparison of the toxicities and medicoeconomical profiles of these treatments is warranted to identify effective replacements for BCNU-based conditioning.