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1.
Biol Blood Marrow Transplant ; 20(5): 717-23, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24525280

RESUMO

Several algorithms for early prediction of poor-mobilizing patients after chemotherapy and granulocyte colony-stimulating factor administration have been proposed. They generally define peripheral blood cut-off levels of CD34+ cells at a fixed day after starting chemotherapy, mostly with cyclophosphamide. To define an algorithm for early addition of plerixafor regardless of the chemotherapy regimen used, we retrospectively analyzed 280 chemomobilization attempts in 236 patients treated at our institution between 2002 and 2012. In multivariate analysis, CD34+ absolute count and CD34+ percentage upon total leukocyte count at day 1 (defined as the first day in which leukocytes reached a value > 1 × 10(9)/L) were the only factors able to predict a total harvest ≥ 2 × 10(6) CD34+/kg. In patients with day 1 CD34+ lower than 20/µL, the CD34+ percentage was a more reliable predictor of stem cell harvest in the following days than CD34+ absolute count. Upon definition of the best CD34+ cut-off value for identification of poor-mobilizing patients, an algorithm was set up to guide plerixafor administration. It was prospectively validated in 20 patients in 2013 with encouraging results in terms of low incidences of both mobilization failure and plerixafor use. Large prospective trials that define the most cost-effective strategy for just-in-time rescue plerixafor are warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Compostos Heterocíclicos/uso terapêutico , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Transplante de Células-Tronco de Sangue Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Idoso , Antígenos CD34/metabolismo , Benzilaminas , Biomarcadores/metabolismo , Ciclamos , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/imunologia , Doença de Hodgkin/patologia , Humanos , Contagem de Leucócitos , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos Retrospectivos , Fatores de Tempo , Transplante Autólogo
3.
Clin Case Rep ; 9(3): 1066-1071, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33768784

RESUMO

Abnormal NIPT results, contrasting with normal fetus development, could disclose maternal malignancy, and this possibility should always be explained during pretest counseling. In this case, a complete diagnostic assessment is recommended and should be managed by a multidisciplinary team to define the best timing for diagnostic procedures, delivery, and treatment.

4.
Transplant Cell Ther ; 27(5): 406.e1-406.e11, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965179

RESUMO

HLA molecules are important for immunoreactivity in allogeneic hematopoietic stem cell transplantation (HSCT). The Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti promoted a retrospective observational study to evaluate HLA matching and the impact of allelic HLA mismatching and non-HLA factors on unrelated Italian HSCT outcomes. From 2012 to 2015, 1788 patients were enrolled in the study. The average donor age was 29 years and the average recipient age was 49 years. As a conditioning regimen, 71% of the patients received myeloablative conditioning. For GVHD prophylaxis, 76% received either antithymocyte or anti-T lymphocyte globulin, cyclosporine A, and methotrexate. Peripheral blood was the stem cell source in 80%. The median duration of follow-up was 53 months. Regarding HLA matching, 50% of donor-recipient pairs were 10/10 matched, 38% had 1 mismatch, and 12% had 2 or more mismatches. A total of 302 pairs shared Italian origin. Four-year overall survival (OS), progression-free survival, GVHD-free relapse-free survival, and relapse rates were 49%, 40%, 22%, and 34%, respectively. The 4-year NRM was 27%, and the 100-day cumulative incidence of grade ≥II acute GVHD (aGVHD) was 26%. In multivariate analysis, 9/10 and ≤8/10 HLA allele-matched pairs were associated with worse OS (P = .04 and .007, respectively), NRM (P = .007 and P < .0001, respectively), and grade III-IV aGVHD (P = .0001 and .01, respectively). Moreover, the incidences of grade II-IV aGVHD (P = .001) and chronic GVHD (P = .002) were significantly lower in Italian pairs. In conclusion, 10/10 HLA matching is a favorable prognostic factor for unrelated HSCT outcome in the Italian population. Moreover, the presence of 2 HLA-mismatched loci was associated with a higher NRM (P < .0001) and grade II-IV aGVHD (P = .006) and a poorer OS (P = .001) compared with 1 HLA-mismatched locus in early or intermediate disease phases. Finally, we found that Italian donor and recipient origin is a favorable prognostic factor for GVHD occurrence.


Assuntos
Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Adulto , Alelos , Medula Óssea , Humanos , Itália , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Sistema de Registros
5.
Pharmaceuticals (Basel) ; 14(1)2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33383757

RESUMO

Elderly transplant-ineligible (NTE) patients represent the majority of patients affected by multiple myeloma (MM). Elderly patients are a highly heterogeneous population, with large variability in health and functional status. Thus, choosing their optimal treatment is challenging. A wide range of first-line treatments is available, and novel-agent combinations, including monoclonal antibodies (mAbs), have recently entered clinical practice. The combination of the anti-CD38 mAb daratumumab with bortezomib, melphalan and prednisone (Dara-VMP) or lenalidomide and dexamethasone (Dara-Rd) demonstrated impressive advantages in terms of progression-free survival and minimal residual disease negativity, as compared to VMP and Rd, without safety concerns. Another anti-CD38 mAb, isatuximab, is showing encouraging results, and new isatuximab-based combinations might enter clinical practice in the future. Nevertheless, available data come from clinical trials with selected patient populations and, to date, the manageability of these regimens in real-life patients or in frail patients remains unknown. Frailty-tailored treatments, including mAbs, are under evaluation in preliminary studies. In this review, we analyze recently approved mAb-based treatments for NTE newly diagnosed MM patients and new combinations under evaluation, focusing on the efficacy and safety of these regimens and on open issues regarding the choice of therapy for elderly patients.

6.
J Med Case Rep ; 14(1): 75, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32564775

RESUMO

BACKGROUND: Immunoglobulin M multiple myeloma and Waldenström macroglobulinemia are two different hematological diseases with the common finding of an immunoglobulin M monoclonal gammopathy of unknown significance. However, clinical characteristics of the two entities can overlap. CASE PRESENTATION: In this report, we describe two cases of immunoglobulin M neoplasm with the same histological bone marrow presentation but with different clinical behavior, cytogenetics, and biological assessment. On the basis of comprehensive diagnostic workup, these patients were considered to have different diseases and treated accordingly with different approaches. Patient 1 (Caucasian man) presented with increased serum protein and immunoglobulin M (7665 mg/L) with an M-spike electrophoresis of 4600 mg/L. His bone marrow biopsy revealed a small-cell immunoglobulin M multiple myeloma. The result of testing for the MYD88 L265P mutation was negative, while fluorescence in situ hybridization analysis showed translocation t(11,14). A diagnosis of immunoglobulin M-κ multiple myeloma was made. Patient 1 was a candidate for bortezomib plus thalidomide and dexamethasone, followed by autologous stem cell transplant consolidation. Patient 2 (Caucasian man) showed an M-spike by protein electrophoresis (300 mg/L, 4.9%), with serum immunoglobulin M level of 327 mg/L. His bone marrow biopsy revealed immunoglobulin M-κ multiple myeloma. Computed tomography showed many enlarged lymph nodes and splenomegaly. Patient 2's clinical features were suggestive of Waldenström macroglobulinemia, in contrast to the bone marrow biopsy results. The result of testing for the MYD88 L265P mutation was positive. Patient 2 was diagnosed with Waldenström macroglobulinemia and received rituximab, cyclophosphamide, and dexamethasone. CONCLUSIONS: A correct differential diagnosis between immunoglobulin M multiple myeloma and Waldenström macroglobulinemia is a critical point in the setting of a new immunoglobulin M monoclonal gammopathy onset. These patients should undergo a complete diagnostic workup with pathological, radiological, and serological examinations to establish the diagnosis and plan the most appropriate treatment in order to improve the prognosis.


Assuntos
Imunoglobulina M/sangue , Mieloma Múltiplo/diagnóstico , Macroglobulinemia de Waldenstrom/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Medula Óssea/patologia , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Mutação , Fator 88 de Diferenciação Mieloide/genética , Rituximab/administração & dosagem , Transplante de Células-Tronco , Talidomida/administração & dosagem
7.
J Hematol Oncol ; 9: 26, 2016 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-26983546

RESUMO

BACKGROUND: Interim positron emission tomography after 2 cycles of ABVD (iPET-2) is a good predictor of outcome in advanced-stage classic Hodgkin lymphoma. So far, there are no other prognostic biomarkers capable of identifying chemotherapy refractory patients with comparable accuracy. Despite the considerable amount of evidence suggesting that antitumor immune surveillance is downregulated in classic Hodgkin lymphoma (cHL), few data exist on the impairment of natural killer cell function and the role of their killer immunoglobulin-like receptors (KIRs). METHODS: We investigated KIR gene frequencies, KIR haplotypes, and KIR-ligand combinations in a cohort of 135 patients with advanced-stage classic Hodgkin lymphoma and 221 healthy controls. We furthermore evaluated the correlation of KIR genes and KIR haplotypes with the achievement of negative iPET-2. RESULTS: In the cohort of patients, the 5-year overall survival and progression-free survival were 93.6 and 79%, respectively. Homozygosity for KIR A haplotype and the HLA-C1 KIR ligand (KIR-AA/C1C1) was significantly higher in healthy controls (15.7 vs. 4.8%, p = 0.001). The KIR-AA genotype resulted to have a significant predictive power for achieving iPET-2 negativity (p = 0.039). CONCLUSIONS: Homozygosity for KIR A haplotype offers protection against classic Hodgkin lymphoma. The association found for the KIR-AA genotype and achievement of negative iPET-2 suggests that KIR-AA could be used in clinical practice to enhance the chemosensitivity predictive power of iPET-2. Our results point to the possibility of adapting treatment strategies based on the combination of KIR biomarkers and PET scan.


Assuntos
Biomarcadores Tumorais/genética , Haplótipos , Doença de Hodgkin/genética , Receptores KIR/genética , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Fluordesoxiglucose F18 , Frequência do Gene , Antígenos HLA/genética , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de Saúde , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Vimblastina/administração & dosagem
8.
Case Rep Hematol ; 2013: 896394, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23936694

RESUMO

Despite major advances in the treatment of acute promyelocytic leukemia (APL), the problem of early death (ED) remains unsolved. Alongside the currently known clinical and hematological risk factors, prognostic significance has been attributed to internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD), hypogranular variant morphology, and the bcr-3 isoform of PML-RAR α . We describe premature death of two patients with the hypogranular variant of APL who presented remarkably high expression levels of Wilms' tumor gene (WT1). Our results point to WT1 as an important prognostic factor of ED that needs to be promptly evaluated in all newly diagnosed cases of APL.

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