Papers by NANCY SOLEDAD CRISTALDO
Transplant Infectious Disease, Jun 17, 2020
Adult T-cell lymphoma is an aggressive and poor prognosis HTLV1 associated lymphoma. There is no ... more Adult T-cell lymphoma is an aggressive and poor prognosis HTLV1 associated lymphoma. There is no standard treatment, but it is known that intensive chemotherapy regimens are necessary, Accepted Article This article is protected by copyright. All rights reserved with or without concomitant antiretroviral therapy, plus consolidation with allogeneic stem cell transplantation. Our case report shows a favorable outcome after 2 cycles of chemotherapy and allogeneic stem cell transplantation without antiretroviral agents, achieving complete remission and a negative proviral load.
Clinical Lymphoma, Myeloma & Leukemia, Sep 1, 2018
Clinical Lymphoma, Myeloma & Leukemia, Sep 1, 2018
Blood, Nov 13, 2019
Classic Hodgkin Lymphoma (cHL) is a germinal center derived lymphoma with 8,500-9,000 new cases/y... more Classic Hodgkin Lymphoma (cHL) is a germinal center derived lymphoma with 8,500-9,000 new cases/year diagnosed in the US. Despite 90% stage I cHL patients can respond to current systemic therapy, this drops to 60%, when diagnosed in advanced stages. Furthermore, 20-30% of diagnosed patients, would be refractory or would relapse and have a poor prognosis. Refractory and relapsed disease (RRD) is currently the challenge when treating cHL patients. There is no specific therapy to offer rather than rescue chemotherapy schemes, which fails in 50% of the cases and associates with high risk severe toxicity. This highlights the need to deeper understand the cHL molecular biology, the screening for molecular markers suitable to identify the risk of refractory and relapse disease and specific therapeutic directed-targets. We have previously reported that the alternative NFkB pathway, mediated by Rel-B and NIK (NFkB Inducing Kinase), plays an important role in cHL survival. Its constitutive activation sustains high BCL2 expression levels and seems to be involved in the RRD. BCL2 was found as a specific Rel-B target gene in cHL cells by ChIP-Seq (Chromatin Immunoprecipitation sequencing) and expression arrays. BCL2 exogenous expression was enough to partially rescue the death induce in cHL cells, which highlight the relevance of this alternative NFkB pathway target gene. Since the BCL2 data was obtained in human cHL cell lines established from patients with refractory and relapsed disease, we decided to analyze whether mediators of this pathway and BCL2 could be useful as prognosis markers and would represent potential targetable factors in both refractory and relapsed disease. We analyzed NIK and BCL2 citoplasm expression in Hodgkin Reed-Sternberg cells (HRS) in the lymph node biopsies of 113 cHL naïve of therapy patients by inmunohistochemistry [52 female Md age and (range) 36 (6-88), 61 male 40.7 (9-78)]. The follow-up period range from 6 to 136 months. The univariate analysis showed no correlation between NIK or BCL2 expression and the prognosis clinical and pathological parameters, including the PET Scan indicated at the end of the first line treatment, neither the molecular markers routinely assayed. The statistical significance was maintained in multivariate analysis (Logistic and Cox Regression p=0.01). NIK expression did not associate with prognosis but the BCL2 expression level correlated with lack of response to conventional therapy and both early and late disease progression. The survival analysis, using the Kaplan-Meir curves, showed that patients with ≥60% positive HRS cells had a shorter disease-free survival (DFS) [Log Rank Test (Mantel Cox) p=0.002] and a reduced overall survival (OS) [Log Rank Test (Mantel Cox) p=0.02]. L1236, U-H01, KM-H2, SUPDH1 and L540, human cHL cell lines that express BCL2 protein, were sensitive to venetoclax, a specific BCL2 inhibitor. The drug induced a cell cycle arrest in S-Phase when treated with 1uM each 24 hours during 10 days, as compared to wild type cells and cells treated with the vehicle. In summary, we found that the alternative NFkB pathway plays a role in the refractory and relapsed classic Hodgkin Lymphoma disease, being BCL2 one of its key downstream target genes. BCL2 can be used as a prognosis marker determined by routine immunohistochemistry at diagnosis of the primary disease. BCL2 expression correlated with refractory disease to first line conventional therapy and disease progression. Based on the venetoclax effect in cHL cell lines we believe BCL2 directed-therapy in cHL should be considered in the subgroup of cHL patients that express this protein in ≥60% HRS cells in the lymph node biopsy performed at diagnosis. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: venetoclax used to specifically block BCL2.
Clinical Lymphoma, Myeloma & Leukemia, Sep 1, 2019
and 6 months, respectively, after diagnosis/starting dasatinib; followed until 5/30/2019. Interve... more and 6 months, respectively, after diagnosis/starting dasatinib; followed until 5/30/2019. Interventions: Lower dose dasatinib 20mg, filgrastim, imatinib, and nilotinib were given to patient 1, who then underwent MRD Allo-SCT and was restarted on nilotinib posttransplant. Patient 2 was given filgrastim, eltrombopag, cyclosporine, and imatinib. Main Outcomes Measures: Transfusion independence, BCR-ABL1 transcript (IS%), hemoglobin, platelets, ANC. Results: Patient 1 was platelet and pRBC transfusion independent for 89 weeks, last BCR-ABL1 undetectable, and last CBC showed ANC 2400, hemoglobin 12.4, platelets 337K. Patient 2 was transfusion independent for 9 weeks for platelets and 19 weeks for pRBCs, last BCR-ABL1 2.4304%, and last CBC showed ANC 1000, hemoglobin 7.7, platelets 24K. Neither patient received growth factors recently. Conclusions: We report two cases of aplastic anemia/pancytopenia 5-6 months after starting dasatinib 100mg for CML induction. Pancytopenia was unaffected by lowering the dose or holding dasatinib. Patient 1 was unable to tolerate imatinib, though patient 2 is so far tolerating it. Nilotinib was given to patient 1 as his CML had transformed to an accelerated phase, though this too caused cytopenias, and was only given briefly as a bridge to transplant (<1 year after AA diagnosis), which was successful. He was restarted on nilotinib post-transplant due to detectable BCR-ABL1 that is now undetectable. Patient 2 was treated initially with filgrastim unsuccessfully, and later given cyclosporine and eltrombopag. Four months later, imatinib was started. Three months later he was transfusion independent. His BCR-ABL1 is downtrending again. Although rare, aplastic anemia should be in the differential diagnosis of patients with CML on TKIs who develop late onset cytopenias.
Hematological Oncology, Jun 1, 2019
systemic disease. They constitute about 3% of the primary central nervous system (CNS) tumors and... more systemic disease. They constitute about 3% of the primary central nervous system (CNS) tumors and about 1% of all NHL. They are diagnosed in patients of all ages, most often in men between 60 and 70 years of age. Histologically, they form a very homogeneous group of lymphomas. The most common (> 95%) are diffuse B-cell large lymhomas (DLBCL) expressing CD20, CD19 and CD79a antigens, which are non-germinal B-cell like (non-GCB). The aim of the study was to assess the significance of neurosurgical procedure scope (total resection, partial resection, biopsy) on overall survival (OS) and progression free time (PFS). Methods: A retrospective study included 50 patients with PCNSL. There were 22 (44%) women and 28 (56%) men, aged 20-87 (mean age 62). Functional status of every patient was assessed using the Karnofsky scale, neurological examination and magnetic resonance imaging (MRI) of the head were performed. The final diagnosis was based on histopathological examination of tissue material obtained during a stereotactic biopsy or total / partial tumor resection. Results: The most frequently diagnosed histopathological type of primary brain lymphoma was DLBCL (46/92%). In the majority of patients, PCNSL was located in the hemispheres of the brain (28/56%) and the corpus callosum (10/20%). Biopsy was performed in 26 (52%), partial resection in 6 (12%) and complete resection in 18 (36%) patients. In the entire study group, median overall survival was 16 months (0-108 months), while progression-free survival was 7.5 months (0-98 months). There was no statistically significant relationship between OS and PFS and the type of neurosurgical procedure performed (total resection, partial resection, biopsy) and the number and location of lymphoma tumors. Conclusions: The lack of significant impact of complete tumor resection on OS and PFS in patients with PCNSL indicates the justifiability of performing it only in a selected group of patients, singled out on the basis of the neurological status and the location of lesions in the CNS.
Clinical hematology international, Jun 1, 2022
There are no data in Argentina on the response rates to first-line treatment of classical Hodgkin... more There are no data in Argentina on the response rates to first-line treatment of classical Hodgkin Lymphoma (cHL) outside clinical trials. A total of 498 patients from 7 public and private hospitals in Argentina were retrospectively examined. The median follow-up was 37.4 months (CI 95% 17.7-63.5). The median time from diagnosis to treatment was 22 days (IQR 14-42), which was significantly longer in public hospitals (49.3 (IC 95% 38.5-60.2) versus 32.5 (IC 95% 27-38); p = 0.0027). A total of 96.8% of patients were treated with ABVD.:84.3% achieved complete remission (CR) and 6.02% partial remission (PR), being the CR rate higher in private hospitals. End-of-treatment metabolic CR was achieved in 85.4% (n = 373). The interim PET scan was widely used in our cohort (70.5%; n = 351), but in only 23.3% (n = 116) was the treatment strategy response-adapted. The 5-year progression-free survival (PFS) was 76% (CI 95% 70-81). The 2 and 5-years-OS rates were 91% (CI 95% 88-94%) and 85% (CI 95% 80-89%), respectively. No differences in OS were found between public and private institutions (p = 0.27). This is one of the largest retrospective cHL cohorts reported. In Argentina ABVD is the chemotherapy regimen of choice and, although it is well tolerated, it is not exempt from toxicity. We showed that early initiation of treatment impacts the induction results. Although the use of PET scan is widespread, only a minority of patients was treated with respons-adapted strategies. The use of PET-guided treatment is strongly encouraged.
Blood, 2021
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype... more Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype. Early stage (I/II) disease is seen in up to 30% of all DLBCL cases, and although outcomes in this subgroup have been reported as optimal, relapses can still occur. Prognostic models such as the International Prognostic Index (Miller, NEJM, 1998) continues to be utilized for risk stratification in DLBCL. However, despite its limitations and lack of validation in specific demographic groups such as Latin American patients, no prognostic models exist for the evaluation of limited stage DLBCL. Therefore, we aim to investigate different clinico-epidemiological and laboratory variables and its impact on survival in early stage DLBCL. Methods: We conducted a retrospective study of newly diagnosed patients with early stage DLBCL. Using the Grupo de Estudio Latinoamericano de Linfroproliferativos (GELL) database, we selected patients that had early stage disease, defined as non-bulky stage I or...
Blood, 2021
Updated analysis confirms sustained poor prognosis of COVID-19 in patients with lymphoma in Latin... more Updated analysis confirms sustained poor prognosis of COVID-19 in patients with lymphoma in Latin America: A cohort of 160 patients from GELL. Introduction: Ongoing SARS-COV-2 pandemic has impacted the management of cancer patients worldwide. Several reports have demonstrated inferior outcomes of patients with hematological malignancies, including higher rates of intensive care unit admission, need for mechanical ventilation and death. The impact of COVID-19 is profound in resource-restricted countries, including Latin America. Most cohorts reported have not included patients from Latin America, and there is paucity of data of the outcome of cancer patients with COVID-19 in low- and middle-income countries. Grupo de Estudio De Linfoproliferativos En Latino-America (GELL )is a collaborative network of hematological centers in 13 countries in Latin America. We report updated outcomes of lymphoma patients diagnosed with COVID-19 in Latin America. Methods: We conducted a retrospective s...
Blood, 2020
INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm c... more INTRODUCTION: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell neoplasm caused by the Human T-cell Leukemia Virus Type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, Western Africa, the Caribbean basin and South America. Cutaneous signs of ATLL are varied and may consist of macules (M), plaques (P), multiple papules (MP), tumoral nodules (TN), erythroderma (E) or mixed-lesions (≥2 predominant lesions, ML). M and P forms are believed to carry a better prognosis. However, data on cutaneous presentation of ATLL remains scarce. Herein, we report cases of ATLL with cutaneous involvement diagnosed in 4 Latin American countries over the last 3 decades. METHODS: We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1995 and December 2019. ATLL subtypes were classified according to the Shimoyama criteria into acute, lymphomatous, chronic and smoldering. Primary cutaneous tumoral (PCT) va...
Blood, 2020
Introduction: SARS-COV-2 pandemic has infected approximately 20 million people worldwide and more... more Introduction: SARS-COV-2 pandemic has infected approximately 20 million people worldwide and more than 700.000 fatalities have been reported. Patients with malignant hematological diseases are at particular risk for unfavorable outcomes, including intensive care unit (ICU) admission, need for mechanical ventilation (MV) and death. There is paucity of data of the outcome of cancer patients with COVID-19 in low- and middle-income countries. GELL is a collaborative network of hematological centers in 13 countries in Latin America. In this retrospective study, we aimed to look at the outcome of lymphoma patients diagnosed with COVID-19 in Latin America. Methods: This is a retrospective study including patients with a diagnosis of lymphoma and COVID-19 infection. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma were excluded from the analysis. COVID-19 diagnosis was done by RT-PCR in all but 3 patients, in whom the diagnosis was done by serology. Active disease was d...
Blood, 2020
Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma subtype s... more Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma subtype seen in Western countries. However, data on FL from Latin America (LATAM) are scarce. We aimed at better understanding the clinical features, treatment patterns and outcomes of patients with FL from LATAM. Methods: This is a retrospective study that included all consecutive patients with a pathological diagnosis of FL at 18 participating centers from 12 LATAM countries. All cases were reviewed by specialized pathologists at their respective participating centers. Pertinent clinical, pathological and treatment data were collected. Responses were assessed per the Lugano criteria. Time to first treatment, progression-free survival after first treatment (PFS1) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: A total of 763 patients were included in this analysis. On clinical features, 51% of patients were ≥60 years, 46% were male, 29% had extranodal involvement...
Blood, 2020
Introduction. There are different scoring systems to differentiate risk groups in patients with D... more Introduction. There are different scoring systems to differentiate risk groups in patients with DLBCL treated with chemoimmunotherapy. Those systems have used the same 5 variables (age, performance status, LDH, stage, extranodal involvement) for 27 years. However, LATAM data have not been included in the development of previous scoring systems. It is important to mention that novel biological variables, such as albumin, beta-2-microglobulin (B2M) and platelet/lymphocyte ratio (PLR), have been reported and could improve discrimination (Villela et al. Blood 2019; 134Suppl_1: 1613). Therefore, we carried out a large, multinational study to develop and validate a LATAM-IPI score. Methods. This is a retrospective cohort of 1030 patients with a diagnosis of DLBCL treated with standard chemoimmunotherapy with curative intent between 2010 and 2018. Data were obtained from 8 LATAM countries: Argentina, Colombia, Chile, Guatemala, Mexico, Paraguay, Peru, and Venezuela. The five classic IPI va...
JCO Global Oncology
PURPOSE Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell... more PURPOSE Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease caused by the human T-cell leukemia virus type 1. Real-world data of ATLL in Latin America are lacking. PATIENTS AND METHODS We analyzed patients with ATLL (acute, lymphomatous, chronic, and smoldering) encountered in 11 Latin American countries between 1995 and 2019. Treatment response was assessed according to the 2009 consensus report. Survival curves were estimated using the Kaplan-Meier method and log-rank test. RESULTS We identified 253 patients; 226 (lymphomatous: n = 122, acute: n = 73, chronic: n = 26, and smoldering: n = 5) had sufficient data for analysis (median age 57 years). Most patients with ATLL were from Peru (63%), Chile (17%), Argentina (8%), and Colombia (7%). Hypercalcemia was positively associated with acute type (57% v lymphomatous 27%, P = .014). The median survival times (months) were 4.3, 7.9, 21.1, and not reached for acute, lymphomatous, chronic, and smoldering forms, with 4-year surv...
Revista de la Facultad de Ciencias Medicas, 2021
Introduction CNS relapse in patients with LDCGB is a poor prognosis event. The incidence of relap... more Introduction CNS relapse in patients with LDCGB is a poor prognosis event. The incidence of relapse is variable according to the literature. Data in Latin America is lacking. Methods In order to establish the incidence of CNS relapse in our cohort, time to CNS relapse and the impact of CNS relapse risk factors, a retrospective cohort study was performed, from January 2012 to June 2017. Results One hundred and forty seven patients were analyzed. The median age was 66 years (ICR 56-76); 76 patients (51.70%) were men. The IPI was low or intermediate/low in 115 (78.2%) cases. The CNS IPI was intermediate in 77 (52.4%) and high in 14 (9.5%) of cases. Thirty-five (23.81%) patients received intrathecal prophylaxis. No patient received systemic prophylaxis. During the follow-up, 8 (4.59%) patients had CNS relapse, none of them with high IPI. The median time to relapse was 6.5 months (ICR 5.5-10). Seven (87.5%) patients relapsed within the year of diagnosis. We found no risk factors for CNS ...
Blood, 2021
Introduction: The neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that ap... more Introduction: The neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in different cancers. Although the exact mechanism remains to be elucidated, reduced lymphocyte intra tumor infiltration coupled with the formation of neutrophil extracellular traps (or NETosis) have been postulated as endogenous mechanisms for tissue damage and inflammation. Along this line, serum albumin has also been studied as a biomarker of inflammation and has been associated to prognosis in certain cancers. We have previously reported on the prognostic value of the NLR and serum albumin in diffuse large B-cell lymphoma (Villela, ASH meeting, 2019; Castro, ASH meeting, 2019) and peripheral T-cell lymphoma, not otherwise specified (Idrobo, ASH meeting, 2019), but nothing on follicular lymphoma (FL) yet. Therefore, we aim to investigate the role of different biomarkers on the prognosis of patients with FL diagnosed and managed in Latin America. Methods: We analyzed p...
Life Sciences, 2021
The challenge in classical Hodgkin Lymphoma (cHL) management is the 30-40% of refractory/relapsed... more The challenge in classical Hodgkin Lymphoma (cHL) management is the 30-40% of refractory/relapsed cases.
Clinical Lymphoma Myeloma and Leukemia, 2018
We chose a common therapeutic agent, fludarabine, a purine analog, which does not require any dos... more We chose a common therapeutic agent, fludarabine, a purine analog, which does not require any dose adjustment for hepatic impairment on FDA approved labeling. Notably our patient did achieve a partial response to FR and a concurrent improvement in liver enzymes after one cycle of combination fludarabine and rituximab. Fludarabine, with or without rituximab has been used effectively as a first line regimen in patients with chronic lymphocytic leukemia, eliciting significant complete responses and has also been extensively used in low-grade B-cell lymphoma. Concerns have been raised about the tolerability and long-term toxicity of fludarabine. An alternative purine analog, pentostatin, purports advantages including improved tolerability and less myelosuppression. With limited available data regarding appropriate frontline therapy for patient with aggressive NHL and severe hepatic dysfunction, purine analogs provide a practical treatment approach either as a first line regimen or as a bridging therapy.
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Papers by NANCY SOLEDAD CRISTALDO