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Purpose: BCR::ABL1 quantification is widely regarded as the standard for monitoring measurable residual disease (MRD) in Philadelphia chromosome-positive (Ph+) ALL. However, recent evidence of BCR::ABL1 multilineage involvement questions the significance of BCR::ABL1 MRD. We aimed to define the prognostic role of MRD as assessed by BCR::ABL1 or lymphoid-specific immunoglobulin/T-cell receptor ( IG/TR ) gene markers., Patients and Methods: We conducted BCR::ABL1 and IG/TR quantification after each treatment cycle in 264 patients treated in the GRAAPH-2014 trial, which used four cycles of reduced-intensity chemotherapy with nilotinib, followed by hematopoietic stem-cell transplantation (HSCT)., Results: Comparing BCR::ABL1 and IG/TR MRD revealed residual BCR::ABL1 -positive non-ALL cells in 98 (43%) of 228 patients, defining multilineage Ph+ ALL. Despite poorer BCR::ABL1 responses, patients with multilineage Ph+ ALL had similar disease-free survival (DFS; hazard ratio [HR], 0.83 [95% CI, 0.49 to 1.41]; P = .50). Although BCR::ABL1 response failed to predict outcomes, IG/TR positivity (≥0.01%) was strongly associated with lower DFS (after cycle 2, HR, 2.49 [95% CI, 1.40 to 4.40]; P = .002; after cycle 4, HR, 4.13 [95% CI, 1.82 to 9.38]; P = .001). In multivariable analysis, both IG/TR positivity after cycle 2 and initial WBC count ≥30 × 10 9 /L predicted poorer DFS, enabling to define a high-risk group having a 4-year DFS of 56.5% compared with 87.6% (HR, 3.72 [95% CI, 1.93 to 7.15]; P < .001). Moreover, allogeneic HSCT significantly improved DFS in the high-risk group (HR, 0.33 [95% CI, 0.18 to 0.60]; P < .001), whereas the standard-risk group had favorable outcomes regardless of allogeneic HSCT., Conclusion: Our findings challenge the significance of BCR::ABL1 monitoring in adult Ph+ ALL and demonstrate the prognostic role of IG/TR MRD. This study provides a framework for using MRD to guide treatment strategies in adults with Ph+ ALL.

Background: 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) positron emission tomography combined with low-dose computed tomography (PET/CT) can be used at diagnosis to identify myeloma-defining events and also provides prognostic factors. The aim of this study was to assess the prognostic significance of baseline [ 18 F]FDG PET/CT visual IMPeTUs (Italian myeloma criteria for PET Use)-based parameters and/or total metabolic tumor volume (TMTV) in a single-center population of patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation., Methods: Patients with MM who underwent a baseline [ 18 F]FDG PET/CT were retrospectively selected from a large internal database of the University Hospital of Liege (Liege, Belgium). Initially, all PET/CT images were visually analyzed using IMPeTUs criteria, followed by delineation of TMTV using a semi-automatic lesion delineation workflow, including [ 18 F]FDG-positive MM focal lesions (FL) with an absolute SUV threshold set at 4.0. In a first step, to ensure PET/CT scans accurate reporting, the agreement between two nuclear medicine physicians with distinct experience was assessed. In the second step, univariable and multivariable analyses were conducted to determine the prognostic significance of [ 18 F]FDG PET/CT parameters on progression free survival (PFS) and overall survival (OS), respectively., Results: A total of 40 patients with NDMM were included in the study. The observers agreement in the analysis [18F]FDG PET/CT images was substantial for the presence of spine FL, extra spine FL, at least one fracture and paramedullary disease (Cohen's kappa 0.79, 0.87, 0.75 and 0.64, respectively). For the presence of skull FL and extramedullary disease the agreement was moderate (Cohen's kappa 0.56 and 0.53, respectively). Among [ 18 F]FDG PET/CT parameters, a high number of delineated volumes of interest (VOI) using the SUV4.0 threshold was the only independent prognostic factor associated with PFS [HR (95% CI): 1.03 (1.004-1.05), P = 0.019] while a high number of FL (n > 10; F group 4) was the only independent prognostic factor associated with OS [HR (95% CI): 19.10 (1.90-191.95), P = 0.01]., Conclusion: Our work confirms the reproducibility IMPeTUs criteria. Furthermore, it demonstrates that a high number of FL (n > 10; IMPeTUs F group 4), reflecting a high [ 18 F]FDG-avid tumor burden, is an independent prognostic factor for OS. The prognostic value of the TMTV delineated using a SUV4.0 threshold was not significant. Nevertheless, the count of delineated [ 18 F]FDG-avid lesions VOI using a SUV4.0 threshold was an independent prognostic factor for PFS., (© 2024. The Author(s).)

Background: : Hereditary leiomyomatosis (HL) is an autosomal dominant condition due to a variety of fumarate hydratase (FH) mutations in which individuals tend to develop cutaneous leiomyomas, multiple uterine leiomyomas and are at risk for developing aggressive papillary renal cell carcinoma., Case Presentation: : A 26-year-old man with a past history of acute lymphoblastic leukemia (T-ALL) presented with numerous painful light brown papules and nodules spread all over his body except for the head, appearing since infancy. Similar lesions were present in his mother's family. A cutaneous biopsy revealed a cutaneous leiomyoma. His mother died from metastatic uterine neoplasia and his sister suffered from leiomyoma of the uterus. No renal cancer was reported in his family. A heterozygous pathogenic variant was detected in the FH gene., Conclusion: : To our knowledge, this is the first case possibly linking HL and T-ALL through FH deficiency.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Firstline immunochemotherapy cures approximatively 60 % of patients. The prognosis of patients with refractory disease or with relapsed disease within the first two years after the end of treatment is highly unfavourable. Since June 2019, a new third-line treatment with CAR T cells (chimeric antigen receptor T cells) seems to completely modify the prognosis of these patients. A significant proportion of long-lasting complete responses is obtained with this revolutionary treatment. Quick specialized intervention is required for the unique side effects of this therapy.

Acute leukemias are a heterogeneous group of malignant hemopathies which are subdivided according to the cytological orientation of the pathological blast cell into lymphoblastic (ALL) and myeloblastic (AML) acute leukemias. Recent advances in the biological and genetic understanding of these diseases have led to improved treatments. Specific chemotherapy treatment or so-called «targeted» treatments, advances in bone marrow transplantation and better supportive care have gradually improved the prognosis. This review, focused on the adult patient, aims to describe recent progress in terms of diagnosis, prognostic markers and therapy.

The detection rates of whole-body combined [ 18 F]NaF/[ 18 F]FDG positron emission tomography combined with computed tomography (PET/CT), CT alone, whole-body magnetic resonance imaging (WB-MRI), and X-ray were prospectively studied in patients with treatment-requiring plasma cell disorders The detection rates of imaging techniques were compared, and focal lesions were classified according to their anatomic location. Twenty-six out of 30 initially included patients were assessable. The number of focal lesions detected in newly diagnosed patients (n = 13) and in relapsed patients (n = 13) were 296 and 234, respectively. The detection rate of PET/CT was significantly higher than those of WB-MRI (P < 0.05) and CT (P < 0.0001) both in patients with newly diagnosed and in those with relapsed multiple myeloma (MM). The X-ray detection rate was significantly lower than those of all other techniques, while CT detected more lesions compared with WB-MRI at diagnosis (P = 0.025). With regard to the infiltration patters, relapsed patients presented more diffuse patterns, and more focal lesions located in the limbs compared with newly diagnosed patients. In conclusion, the detection rate of [ 18 F]NaF/[ 18 F]FDG PET/CT was significantly higher than those of CT, MRI, and X-ray, while the detection rate of X-rays was significantly lower than those of all other imaging techniques except for focal lesions located in the skull., (© 2019 John Wiley & Sons, Ltd.)

An observational study was set up to assess the feasibility of [ 18 F]FPRGD 2 PET/CT for imaging patients with multiple myeloma (MM) and to compare its detection rate with low dose CT alone and combined [ 18 F]NaF/[ 18 F]FDG PET/CT images. Four patients (2 newly diagnosed patients and 2 with relapsed MM) were included and underwent whole-body PET/CT after injection of [ 18 F]FPRGD 2 . The obtained images were compared with results of low dose CT and already available results of a combined [ 18 F]NaF/[ 18 F]FDG PET/CT. In total, 81 focal lesions (FLs) were detected with PET/CT and an underlying bone destruction or fracture was seen in 72 (89%) or 8 (10%) FLs, respectively. Fewer FLs (54%) were detected by [ 18 F]FPRGD 2 PET/CT compared to low dose CT (98%) or [ 18 F]NaF/[ 18 F]FDG PET/CT (70%) and all FLs detected with [ 18 F]FPRGD 2 PET were associated with an underlying bone lesion. In one newly diagnosed patient, more [ 18 F]FPRGD 2 positive lesions were seen than [ 18 F]NaF/[ 18 F]FDG positive lesions. This study suggests that [ 18 F]FPRGD 2 PET/CT might be less useful for the detection of myeloma lesions in patients with advanced disease as all FLs with [ 18 F]FPRGD 2 uptake were already detected with CT alone.

We conducted a randomized study analyzing the impact of darbepoetin alfa (DA) administration with or without intravenous (i.v.) iron on erythroid recovery after autologous hematopoietic cell transplantation (HCT). Patients were randomized between no DA (Arm 1), DA 300 μg every 2 weeks starting on Day 28 after HCT (Arm 2), or DA plus i.v. iron 200 mg on Days 28, 42, and 56 (Arm 3). The proportion achieving complete hemoglobin (Hb) response within 18 weeks (primary end point) was 21% in Arm 1 (n = 24), 79% in Arm 2 (n = 25), and 100% in Arm 3 (n = 23; P < 0.0001). Erythropoietic response was shown to be significantly higher in Arm 3 (n = 46) than in Arm 2 (n = 50; P = 0.008), resulting in lower DA use, reduced drug costs, and improved quality of life scores, but the effect on transfusions was not significant. In multivariate analysis, DA administration (P < 0.0001), i.v. iron administration (P = 0.0010), high baseline Hb (P < 0.0001), and low baseline creatinine (P = 0.0458) were independently associated with faster achievement of complete Hb response. In conclusion, DA is highly effective to ensure full erythroid reconstitution after autologous HCT when started on Day 28 post-transplant. I.v. iron sucrose further improves erythroid recovery., (Copyright © 2013 Wiley Periodicals, Inc.)

The prevalence of monoclonal gammopathy of undetermined significance (MGUS) is generally estimated at 3.4% in the general population over 50 years, and its incidence increases with age. MGUS represents a preneoplastic entity that can transform into multiple myeloma or other lymphoproliferative disorders. The risk of malignant transformation is estimated at 1% per year and persists over time. Predictors of malignant transformation have been identified such as the heavy chain isotype, The level of monoclonal proteins, increasing levels of the monoclonal component during the first years off follow-up, the percentage of bone marrow plasmocytosis, the dosage of serum free light chains, the presence of immunophenotypically abnormal plasma cells, aneuploidy, and the presence of circulating plasma cells. Prognostic scores that combine certain of these factors have been proposed and allow the identification of high-risk patients. Their use could assist in tailoring the care for each patient, based on his/her risk profile.

Chronic myelomonocytic leukemia (CMML) is a disease typically of the elderly. It is suspected when monocytosis reaches 1000/microl. It may be associated with "B" symptoms (fever, sweating, and weight loss) but also visceral, skin and autoimmune complications. Current treatment strategies aim at reducing the symptoms and have no curative goals. In this context hypomethylating agents have shown a good efficacy. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option but remains difficult to perform in elderly patients population, even if transplantation with a reduced intensity conditioning has reduced the risks. A new prognostic scoring helps to recognize the patients with poor prognosis and to better selected candidates for the HSCT.

We report the case of a multi-metastatic mucinous adenocarcinoma of the colon discovered pre-mortem in a patient with a history of multiple myeloma. This case gives the opportunity to discuss the prognostic value of histological typing of colorectal cancer and secondary neoplasms to chemotherapy and/or immunodepression.

We report the case of a 24-yr-old woman treated for lymphoma who developed bleomycin-induced interstitial pneumonia. This interstitial pneumonia was complicated by spontaneous pneumomediastinum. Pneumomediastinum is an unfrequent side effect of high dose bleomycin-induced pneumonitis (BIP) and we describe the first case occurring with low-dose of bleomycin.

Diffuse Large B Cells Lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and comprises a large number of different entities with different clinico-pathological characteristics. The role of positron emission tomography is essential during the initial staging and post treatment assessment, and potentially at early- or mid-treatment evaluation of response. First line therapy comprises immuno-chemotherapy with rituximab and different cytotoxic agents that differ for components, dosages and frequency of administration taking worldwide-recognized pre-treatment prognostic variables into account. After relapse, peripheral blood stem cells transplantation remains the only chance of cure. This review attempts to summarize the current state of our knowledge by highlighting the leads pursued to further improve current therapeutic results.

Mantle cell lymphoma is a rare form of non Hodgkin lymphomas. Diagnosis is made by demonstrating a typical immunophenotype as well as the presence of a translocation between chromosomes 11 and 14 with overexpression of cyclin D1. First line therapy for young patients consists in 3 cycles of "R-CHOP21" alternated with 3 "R-DHAP21" and followed by an autograft conditioned by total body irradiation, cyclophosphamide and aracytine. For patients over 65 years of age, the treatment of choice consists in 8 cycles of "R-CHOP21". Maintenance treatment is under evaluation. Allografting is the only chance of cure in relapsed patients with good performance status. Targeted therapies will improve the prognosis of this disease.

Treatment of myelodysplastic syndromes (MDS) has improved in recent years with better results of allogeneic stem cell therapy (SCT), the advent of new therapeutic options such as hypomethylating agents and lenalidomide, the introduction of iron chelation therapy and the implication of erythropoietic stimulating agents in the treatment of anemia. In this review, we summarize the different diagnostic and prognostic criteria and outline the different treatment options we have in 2011.

There is very limited data on isolated systemic relapses of primary central nervous system lymphomas (PCNSL). We retrospectively reviewed the clinical characteristics and outcome of 10 patients with isolated systemic disease among 209 patients with PCNSL mainly treated with methotrexate-based chemotherapy (CT) with or without radiation therapy (RT). Isolated systemic relapse remained rare (4.8%, 10/209 patients). Median time from initial diagnosis to relapse was 33 months (range, 3-94). Sites of relapse were mostly extranodal. Three patients presented with early extra-cerebral (EC) relapse 3, 5 and 8 months from the beginning of initial treatment, respectively, and 7 patients had later relapses (range, 17-94 months). Treatment at relapse included surgery alone, RT alone, CT with or without radiotherapy, or CT with autologous stem cell transplantation (ASCT). Median overall survival (OS) after relapse was 15.5 months (range, 5.8-24.5) compared to 4.6 months (range, 3.6-6.5) for patients with central nervous system (CNS) relapse (p = 0.35). In conclusion, isolated systemic relapses exist but are infrequent. Early EC relapse suggests the presence of systemic disease undetectable by conventional evaluation at initial diagnosis. Patient follow-up must be prolonged because systemic relapse can occur as late as 10 years after initial diagnosis. Whether EC relapses of PCNSL have a better prognosis than CNS relapses needs to be assessed in a larger cohort., (Copyright © 2010 John Wiley & Sons, Ltd.)

Mantle cell lymphoma comprises 3 to 10% of non-Hodgkin's lymphomas. Cyclin D1 expression due to t(11 ;14) (q13 ;32) is considered as a hallmark of this lymphoma and plays a pivotal role in the pathophysiology of lymphoma transformation. Median age at diagnosis ranges from 60 to 70 years, and diagnosis is often made at an advanced stage with widespread lymphadenopathy and extranodular (particularly bone marrow and gastrointestinal) infiltration. First line treatment consists of combination chemotherapy followed with autologous hematopoietic cell transplantation (HCT) in younger patients, while allogeneic HCT following non-myeloablative conditioning might have a role in patients relapsing after autologous HCT.

We report the occurrence of a cerebral toxoplasmosis 52 days after a non-myeloablative allogeneic stem cell transplantation as treatment for acute myeloid leukemia.

Directed against the CD20 antigen on B lymphocytes, rituximab (MabThera) is now incorporated in the first line therapy of symptomatic follicular as well as diffuse large B cell non-Hodgkin's lymphoma and offers superior response and survival rates. 90Y ibritumomab tiuxetan (Zevalin) combines the specificity of rituximab for the CD20 antigen and the therapeutic effect of beta irradiation. Given in monotherapy, it constitutes an interesting alternative therapy for follicular lymphomas in second relapse. Alemtuzumab (MabCampath) recognizes the CD52 antigen and offers encouraging results in chronic lymphocytic leukemia resistant to classical chemotherapy.

In their later stages low grade lymphoma are incurable. These lymphomas being radio-sensitive, a treatment of metabolic radioimmunotherapy, using monoclonal antibodies (anti-CD20) as the carrier has been developed. The aim of this treatment is to use these antibodies to target radiation to tumor tissues while limiting toxicity to normal cells. Ibritumomab tiuxetan (Zevalin) is currently prescribed for patients with relapsed or refractory low-grade follicular lymphoma after rituximab treatment. This outpatient treatment has a high level of overall response rate including complete response and that for a long period. The side effects are essentially hematological and reversible. In the near future many more indications should become apparent and Zevalin should become an important tool in the B-cell lymphoma (low and high grade).

This article describes the treatment of acute myeloid leukemia in older patients with good performance status, and then discusses briefly some future therapeutic perspectives.

This article focuses on recent advances in four important areas of hematology: aggressive lymphomas, allogeneic hematopoietic stem cell transplantation, multiple myeloma, and molecular therapy of cancer.

Occurrence of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL), clinically referred to as Richter's syndrome, occasionally manifests as a lymphoproliferation resembling Hodgkin's lymphoma (HL) and often containing the Epstein-Barr virus (EBV). Only a limited number of HL variants have been subject to informative analysis regarding their clonal relationship to the CLL, with evidence of a same clonal origin in some cases and of clonally unrelated neoplasms in other cases. In this paper, we performed a detailed pathologic, virologic, and molecular analysis of two cases of Richter's syndrome with HL features. The first case occurred in a 65-year-old man with a 5-year history of CLL as a mediastinal and supraclavicular mass histologically diagnosed as lymphocyte depleted HL with no background CLL. The second case occurred in a 78-year-old woman with a 4-year history of CLL as an inguinal mass with a composite histologic appearance comprising areas of CLL, areas of CLL with Hodgkin Reed-Sternberg cells, and areas of HL. Both patients had received fludarabine therapy. The HRS cells were CD20-/CD30+/CD15-/J-chain- in case no. 1 and CD20+/-/CD30+/CD15-/J-chain- in case no. 2. In both cases, the Hodgkin's Reed-Sternberg cells (HRS) were positive for type A EBV, and a 30-bp deletion of the LMP-1 gene was detected in case no. 2. Using microdissection and polymerase chain reaction amplification of the immunoglobulin heavy chain gene (IgH) complementarity determining region III of each cell type, we demonstrated a distinct clonal origin for the CLL cells and the HRS in both cases. These cases bring support to the hypothesis that EBV+ HL in CLL patients occurs as unrelated secondary neoplasms most likely as the result of the immune depression associated with CLL and also raise the question of a possible causal role of fludarabine.

In this pilot study; we assessed the immunosuppressive and the antileukemic potential of a combination of busulfan and melphalan prior to allogeneic BMT in 25 adult patients with refractory or relapsed hematological malignancies. Twelve patients were transplanted for acute myeloid leukemia (relapse: five patients; primary refractory: four patients; second remission: two patients), two patients for primary refractory acute lymphoblastic leukemia, nine patients for chronic myelogenous leukemia (accelerated phase: six patients; blastic phase: three patients) and two patients for primary refractory lymphoma. All received an unmanipulated marrow from HLA-identical siblings. All patients but one engrafted (median time to ANC > or = 0.5 x 10(9)/l = 17 days, to platelets > or = 50 x 10(9)/l = 29 days). Full chimerism was documented in the seven evaluable patients. The probability for developing acute GVHD was 58%. Complete remission was obtained in 17/18 measurable patients. With a 42 month median follow-up, eight patients are alive in unmaintained remission. The 4-year probabilities for relapse, survival, and DFS are respectively: 42%, 35%, and 31%. These results show that the combination of busulfan and melphalan ensures an effective immunosuppression allowing long-term engraftment. This regimen can provide long-term disease-free survival in patients with high-risk disease and thus represents an interesting alternative to the CY and/or TBI-containing regimens.