Lactate dehydrogenase as a hematopoietic stem cell mobilization biomarker in autologous transplantation

ABSTRACT Introduction: Pre-apheresis peripheral blood CD34+ cell count (PBCD34+) is the most important predictor of good cell mobilization before hematopoietic stem cell transplantation, albeit flow cytometry is not always immediately available. Identification of surrogate markers can be useful. The CD34+ cells proliferate after mobilization, resulting in elevated lactate dehydrogenase (LDH) activity and correlating with the PBCD34+ count. Objective: To determine the LDH cut-off value at which adequate CD34+ cell mobilization is achieved and its diagnostic yield. Materials and methods: A total of 103 patients who received an autologous stem cell transplantation (ASCT) between January 2015 and January 2020 were included. Demographic and laboratory characteristics were obtained, including complete blood count, pre-apheresis PBCD34+ and LDH levels. Receiver operating characteristic (ROC) curves were performed to identify the optimal serum LDH activity cut-off points for ≥ 2 and ≥ 4 × 106 cells/kg post-mobilization CD34+ count and their diagnostic yield. Results: A post-mobilization serum LDH cut-off value of 462 U/L yielded a sensitivity (Se) = 86.8% (positive predictive value [PPV] = 72.7%), a pre- and post-mobilization serum LDH difference cut-off value of 387 U/L, an Se = 45.7% (PPV = 97%) and an LDH ratio of 2.46, with an Se = 47.1% (PPV = 97%) for an optimal mobilization count (CD34+ ≥ 4 × 106). Conclusion: The LDH measurement represents a fast and affordable way to predict PBCD34+ mobilization in cases where flow cytometry is not immediately available. According to the LDH diagnostic yield, it could be used as a surrogate marker in transplant centers, supporting the CD34+ count, which remains the gold standard.

Outcomes and survival predictors of Latin American older adults with acute myeloid leukemia: Data from a single center

ABSTRACT Introduction: Acute myeloid leukemia (AML) is most commonly presented in older adults; however, it appears 10 years earlier in Latin American countries. Clinical evolution in older adults from this populations has not been characterized. We analyzed outcomes and survival predictors. Methods: Patients ≥ 55 years old diagnosed with AML at a hematology referral center from 2005 to 2020 receiving intensive chemotherapy (IC), low-dose cytarabine (LDAC) and best supportive care (BSC) were included. Survival analysis included the Kaplan-Meier and Cox models and the cumulative incidence of relapse (CIR). Results: Seventy-five adults were included and the overall survival (OS) was 4.87, 1.67 and 1.16 months, using IC, LDAC and BSC, respectively. The IC led to a higher OS (p < 0.001) and was a protective factor for early death, at a cost of more days spent hospitalized and more non-fatal treatment complications; non-significant differences were found between the LDAC and BSC. Eight (10.7%) patients underwent hematopoietic cell transplantation, with a higher OS (p = 0.013). Twenty (26.7%) patients achieved complete remission; 12 (60%) relapsed with a 6-month CIR of 57.9% in those < 70 years old vs. 86.5% in those ≥ 70 years old, p = 0.034. Multivariate analysis showed the white blood cell count (WBC) and IC had a significant impact on the patient survival, whereas chronological age and the Charlson comorbidity index (CCI) did not. Conclusion: AML in low-middle income countries demands a different approach; the IC improves survival, even with a high incidence of relapse, and should be offered as first-line treatment. Eligibility criteria should include WBC and a multidimensional evaluation. The age per se and the CCI should not be exclusion criteria to consider IC.

Monthly variation in diagnosis of acute lymphoblastic leukemia and survival outcome in children and adults: 15-year trends at a single center

ABSTRACT Background: The date of acute lymphoblastic leukemia (ALL) diagnosis has been studied regarding potential etiologic roles with contrasting results and the issue remains controversial. The principal aim of this study was to analyze monthly variation of ALL diagnosis in a large homogenous Hispanic Latin American cohort over 15 years; its association with survival rates was also assessed. Methods: Clinical files and electronic records of 501 consecutive patients of all ages with ALL in northeastern Mexico over the years of 2004-2018 were scrutinized. Patients were divided into children <18 and adults >18 years. The Chi-square heterogeneity analysis was used to test for non-uniform variation. The Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data, using the month of diagnosis as a covariate in a separate model. Results: During the study period 363 children (72.5%) and 138 adults (27.5%) (p < 0.001) were diagnosed with ALL. Heterogeneity across the months of diagnosis was confirmed (p = 0.019) and the Poisson regression analysis confirmed a significant monthly variation (p < 0.001) (95% CI, 3.024-3.745), a higher annual peak being observed in the month of March (p = 0.002), followed by a second peak in October (p = 0.026). The five-year OS for children was 68.2% (95% CI, 67.64-68.74) and for adults, 43.7% (95% CI, 42.67-44.71) (p < 0.001). No significant association between the month of diagnosis and OS was found (p = 0.789). Conclusion: The monthly variation of ALL diagnosis was documented; these results confirm the heterogeneous behavior of the disease and appear to be consistent with an interplay of environmental and biologic factors. Further studies are needed to examine putative candidate agents.

Outpatient haploidentical hematopoietic stem cell transplant using post-transplant cyclophosphamide and incidence of hemorrhagic cystitis

Abstract Introduction Hemorrhagic cystitis (HC) is a common complication of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), characterized by irritative symptoms of the urinary tract and a higher morbidity and mortality rate. The worldwide incidence is reported between 10% and 70%. The use of alkylating agents and BK viral infection are the most frequent etiologies. The aim of this study was to report the HC incidence in an outpatient haplo-HCST program with a reduced intensity-conditioning (RIC) regimen, cataloguing risk factors, complications and final outcomes. Methods The medical database of patients who received a haplo-HSCT between January 2012 and November 2017 was retrospectively analyzed. Demographic variables, general characteristics and HC incidence were included. Results One hundred and eleven patients were included, 30 (27%) of whom developed HC, most of them (70%) being grade II, with a 30-day (7-149) median time of post-transplant HC onset. The BK virus was detected in 71% of the urine samples analyzed. All HC patients responded to treatment, except two (6.6%), who died due to HC complications. Conclusions There was no difference in the HC incidence or severity, compared to that reported when performing haplo-HSCT in hospitalized patients, although the donor-recipient sex mismatch did relate to a higher HC incidence.

Childhood T-cell acute lymphoblastic leukemia in a single Latin American center: impact of improved treatment scheme and support therapy on survival

ABSTRACT Background and objective T-cell acute lymphoblastic leukemia (T-ALL) in children represents a high-risk disease. There is a lack of studies assessing the outcome of T-ALL in Hispanic populations, in which it is a rare malignancy. We report the characteristics and results of treatment for childhood T-cell ALL in children over 14 years at a Latin American reference center. Material and methods From January 2005 to December 2018, there occurred the analysis of twenty patients ≤ 16 years of age from a low-income open population diagnosed at a university hospital in Northeast Mexico. Clinical and laboratory characteristics, treatment regimens and outcomes were assessed by scrutinizing clinical records and electronic databases. Diagnosis was confirmed by flow cytometry, including positivity for CD-2, 5, 7 and surface/cytoplasmic CD3. Survival rates were assessed by the Kaplan-Meier method. Results There was a male preponderance (70 %), with a 2.3 male-to-female ratio (p= .074), the median age being 9.5 years. Leucocytes at diagnosis were ≥ 50 × 109/L in 13 (65 %) children, with CNS infiltration in 6 (30 %) and organomegaly in 10 (50 %). The five-year overall survival (OS) was 44.3 % (95 % CI 41.96-46.62), significantly lower in girls, at 20.8 % (95 % CI 17.32-24.51) vs. 53.1 % (95 % CI 50.30-55.82), (p= .035) in boys; there was no sex difference in the event-free survival (EFS) (p= .215). The survival was significantly higher after 2010 (p= .034). Conclusion The T-cell ALL was more frequent in boys, had a higher mortality in girls and the survival has increased over the last decade with improved chemotherapy and supportive care.

Revisiting the complete blood count and clinical findings at diagnosis of childhood acute lymphoblastic leukemia: 10-year experience at a single center

Abstract Background Heterogeneity regarding clinical and laboratory findings at diagnosis of acute lymphoblastic leukemia exists. The frequency of complete blood count abnormalities and its combinations, symptoms and physical findings were investigated in Hispanic children from an open population at the diagnosis of acute lymphoblastic leukemia. Methods The patient charts and electronic records of under 16-year-old children diagnosed with acute lymphoblastic leukemia over 10 years at a regional hematology center of a university hospital were analyzed to retrieve data concerning the complete blood count at first evaluation. Type and distribution of abnormal data, frequency of symptoms and physical findings at presentation were documented. Results The records of 203 children aged 0-15 years diagnosed with acute lymphoblastic leukemia from 2006 to 2016 were revisited. The results of the blood workup showed a median white blood cell count of 7120 × 109/L (range: 450-600,000 × 109/L), and a median hemoglobin concentration of 7.5 g/dL (range: 2.4-15.3 g/dL), whereas the median platelet count was 47,400 × 109/L (range: 4000-544,000 × 109/L). Leukocytosis and leukopenia were present in 36.6% and 36.1% of cases, respectively; anemia was diagnosed in 82.9% children. The order of frequency for major clinical symptoms was fatigue 62%, fever 60%, bone and joint pain 39%, hyporexia 33% and weight loss 21%, while main physical findings were hepatomegaly 78%, splenomegaly 63%, lymphadenopathy 57%, pallor 48%, and purpura 30%. Conclusion Data differing from those classically expected at diagnosis of acute lymphoblastic leukemia in children were documented in a cohort of Hispanic children over one decade with a wide spectrum of complete blood count abnormalities, forms of presentation and frequency of physical findings.

High frequency of primary refractory disease and low progression-free survival rate of Hodgkin's lymphoma: a decade of experience in a Latin American center

Abstract Background: Reports dealing with clinical outcomes of classical Hodgkin's lymphoma in low- to middle-income countries are scarce and response to therapy is poorly documented. This report describes the characteristics and clinical outcomes of patients with classical Hodgkin's lymphoma from a single institution in Latin America. Method: A retrospective study was conducted over ten years of patients with classical Hodgkin's lymphoma treated at a referral center. Progression-free and overall survival rates were estimated by Kaplan-Meier analysis. The univariate Cox regression model was used to estimate associations between important variables and clinical outcomes. Main results: One hundred and twenty-eight patients were analyzed. The mean age was 28.5 years. The five-year progression-free and overall survival were 37.3% and 78.9%, respectively. Of the whole group, 55 (43%) were primary refractory cases. Only 39/83 (47%) patients with advanced disease vs. 34/45 (75.6%) in early stages (p-value = 0.002) achieved complete remission. Those with advanced disease had a five-year overall survival of 68.7% vs. 91.8% for early disease (p-value = 0.132). Thirty-one patients relapsed (24.2%) and 20 (64.5%) received a transplant. The hazard ratio for progression with bone marrow infiltration was 2.628 (p-value = 0.037). For death, an International Prognostic Score ≥4 had a hazard ratio of 3.355 (p-value = 0.050) in univariate analysis. Two-thirds of classical Hodgkin's lymphoma patients diagnosed at advanced stages had a low progression-free survival but an overall survival similar to high-income countries. Conclusion: Patients diagnosed with classical Hodgkin's lymphoma in Northeastern Mexico had a significantly low progression-free survival rate and presented with advanced disease, underscoring the need for earlier diagnosis and improved contemporary therapeutic strategies in these mainly young productive-age Hodgkin's lymphoma patients.

Experience with Evans syndrome in an academic referral center

To document the experience of one referral service with patients diagnosed with Evans syndrome, the treatment and response and to briefly review current treatment strategies and results.METHODS: Patients enrolled in this study fulfilled criteria for Evans syndrome. Data were retrieved from the clinical files and electronic databases of the Department of Hematology, Hospital Universitario "Dr. José Eleuterio González". Treatment modalities and response and the use of additional therapies were evaluated. The literature was reviewed in the context of the clinical course of the studied patients.RESULTS: Six patients were diagnosed with Evans syndrome in the study period. Patient 1 was treated with steroids, relapsed twice and was again treated with steroids. Patient 2 treated initially with steroids plus intravenous immunoglobulin was subsequently lost to follow-up. A good response was achieved in Patients 3 and 4, who were treated with steroids plus rituximab; patient 4 also received danazol as a second-line therapy. However both relapsed and subsequently underwent splenectomy at ten and nine months, respectively. One patient, number 5, treated with steroids, danazol and rituximab did not relapse within four years of follow-up and Patient 6, who received steroids plus danazol did not relapse within three years of follow-up.CONCLUSION: Evans syndrome is an uncommon hematologic condition rarely diagnosed and not widely studied. Clinicians must have it in mind when evaluating a patient with a positive direct antiglobulin test, anemia and thrombocytopenia, since prognosis depends on its early recognition and opportune therapy, but even this leads to variable results...

Evaluation of hemoglobin performance in the assessment of iron stores in feto-maternal pairs in a high-risk population: receiver operating characteristic curve analysis

By applying receiver operating characteristic curve analysis, the objective of this study was to see whether hemoglobin levels reflect body iron stores in a group of pregnant women at term who, by using serum ferritin as the reference test, had a high pre-test prob- ability of having iron deficiency anemia. Likewise, we evaluated the ability of hemoglobin and maternal serum ferritin levels to predict iron deficiency anemia in newborns. Methods: Hemoglobin and serum ferritin were measured in 187 pregnant women at term belonging to a group with a high pre-test probability of iron deficiency anemia and their newborns. Women with Hb <11.0 g/dL and newborns with cord Hb <13.0 g/dL were classified as anemic. A serum ferritin <12.0 µg/L in women and a cord blood serum ferritin <35.0 µg/L were considered to reflect empty iron stores. Receiver operating characteristic curve analysis was applied to select the cut-off points that better reflected iron stores. Results: The Hb cut-off point selected by receiver operating characteristic curve analysis in women was <11.5 g/dL (sensitivity: 60.82, specificity: 53.33%, Youden Index: 0.450). Most of the newborns had normal Hb which precluded this analysis. Maternal Hb <11.0 g/dL was the cut-off point that best reflected iron deficiency anemia in newborns (sensitivity: 55.88%, specificity: 57.24%, Youden Index: 0.217). The best cut-off point of maternal serum ferritin to reflect empty iron stores in newborns was <6.0 µg/L (sensitivity: 76.47%, specificity: 31.58%, Youden Index: 0.200). Conclusion: Hemoglobin concentration performed poorly to detect iron deficiency anemia in women at term with high risk for iron deficiency and their newborns.

Use of complementary and alternative medicine by patients with hematological diseases: experience at a university hospital in northeast Mexico

BACKGROUND: Complementary and alternative medicine includes a diverse group of medical and healthcare systems, practices and products not considered part of conventional medicine. Although there is information on unconventional practices in oncological diseases, specific data regarding the use of complementary and alternative medicine by hematology patients is scarce. OBJECTIVE: The aim of this study is to document the prevalence of this modality of unconventional therapy in patients with malignant and benign hematological diseases, particularly children with acute lymphoblastic leukemia. METHODS: An observational study of adult patients and guardians of children with malignant or benign hematological diseases was carried out by applying a structured questionnaire detailing the use and results of the most prevalent complementary and alternative medicine practices. RESULTS: One hundred and twenty patients were included; 104 had malignant and 16 had benign hematological diseases. The use of complementary and alternative medicine was greater in benign diseases but the difference was not statistically significant (64.7% versus 41.7%; p-value = 0.08). Patients and guardians with high school or college educations used these alternative practices more than patients with less schooling (60.7% versus 54.7%; p-value = 0.032). The use of folk remedies was most prevalent followed by herbal preparations and spiritual healing. Sixty-four percent of patients that used these unconventional practices reported improvement in their symptoms and increased capacity to perform daily activities. CONCLUSION: No significant difference was documented between patients with malignant or benign hematological diseases using these alternative practices. The majority of complementary and alternative medicine users reported improvement of the disease or chemotherapy-related symptoms.

Acute lymphoblastic leukemia of childhood presenting as aplastic anemia: report of two cases

Acute lymphoblastic leukemia is the most common malignancy in pediatric patients; its diagnosis is usually easy to establish as malignant lymphoblasts invade the bone marrow and peripheral blood. Some acute lymphoblastic leukemia patients may initially present with pancytopenia and a hypoplastic bone marrow leading to the initial diagnosis of aplastic anemia. In most of these patients clinical improvement occurs, with normalization of the complete blood count within six months, although recovery can also develop a few weeks after initiating steroid therapy. The etiologic relationship between the aplastic anemia features and the subsequent overt development of acute lymphoblastic leukemia has not been established. We describe the cases of two children who presented with severe infection and signs and symptoms of aplastic anemia confirmed by bone marrow aspirate and bone marrow biopsy that developed acute lymphoblastic leukemia thereafter. No specific therapy for aplastic anemia was administered, nevertheless a full spontaneous recovery was observed in both cases. Acute lymphoblastic leukemia was successfully treated with standard chemotherapy, both children remaining in complete remission 16 and 17 months after their initial aplastic anemia diagnosis.

Bone marrow transplantation in a child with hemophagocytic lymphohistiocytosis using a less toxic conditioning regimen

Background. Hemophagocytic lymphohistiocytosis (HLH) is a rare non-neoplastic, frequently fatal disease of childhood. HLA-matched bone marrow transplantation (BMT) can bring about long-term remission and an eventual cure. Methods. We report on the beneficial effect of BMT in a 2-month-old male using a less intensive conditioning regimen. The regimen included busulfan at 4 mg/kg/day (total dose 16 mg/kg), etoposide at 300 mg/m²/day (total dose 900 mg/m²), and cyclophosphamide at 50 mg/kg/day (total dose 150 mg/kg). Prophylaxis for graft-vs.-host disease included methotrexate and cyclosporine. Results. An absolute neutrophil count of 500 µL was noticed on + day 12 (engraftment day). At present, i.e., 400 days after the procedure, the patients is asymptomatic, his physical examination is normal, and a slightly increased level of gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase are the only laboratory abnormalities. Conclusions. In this case, the conditioning regimen was adequate for the eradication of the disease and allowed persistent engraftment without significant toxicity. The results in our patient suggest that a less toxic regiment is feasible and permits rapid engraftment without compromising the effectiveness of chemotheraphy