Palliative Care for Patients With Hematologic Malignancies in a Low-Middle Income Country: Prevalence of Symptoms and the Need for Improving Quality of Attention at the End of Life.

BACKGROUND: Palliative care (PC) for patients with malignant hematological diseases is scarcely documented, particularly in low- and middle-income countries. This study aimed to document PC provided to patients with hematologic malignancies. METHODS: Bidirectional study conducted from July 2016 to June 2019 at the hematology and palliative care departments at a reference center in Northeast Mexico for low-income open population uninsured patients. Clinical records and electronic files of patients with malignant hematological diseases of both sexes and all ages attending an academic hematology center were reviewed. Statistical analysis was performed with the SPSS version 22 program. Acute and chronic leukemias, multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma, and others were included. RESULTS: Five-hundred ten patients were studied, of which 148 (29%) died. Eighty-one (15.88%) patients including 31 (20.9%) who died received PC. Median age at palliative diagnosis was 42 (2-91) years. The most common symptom was pain (69.7%). The most frequent reason for palliative referral was treatment-refractory disease (39%). During the last week of life, 19 (95%) of 20 patients had blood sampling; 17 (85%) received antibiotics; 16 (80%) had a urinalysis performed; 16 (80%) received analgesia, including paracetamol (11, 35.5%) and buprenorphine (7, 22.6%); 10 (50%) received blood products; 9 (45%) were intubated; and central venous catheters were inserted in 5 (25%) patients. CONCLUSIONS: Palliative care was provided to a minority of patients with hematologic malignancies and considerable improvement is required in its timely use and extension.

Survival Rates of Adults With Acute Lymphoblastic Leukemia in a Low-Income Population: A Decade of Experience at a Single Institution in Mexico.

BACKGROUND: The therapeutic progress for adults with acute lymphoblastic leukemia (ALL) has been slow, with a 5-year survival of 30% to 45% in developed countries. Scarce information is available regarding the treatment and survival rates from nonindustrialized populations. In the present study, the characteristics of adults with ALL at a single institution were documented. PATIENTS AND METHODS: The clinical files of patients aged ≥ 18 years who had been diagnosed with ALL from 2005 to 2015 at a reference center in Mexico were scrutinized. Overall survival (OS) and event-free survival (EFS) were determined using the Kaplan-Meier method. The hazard ratios for death and relapse were estimated using Cox regression analysis. RESULTS: A total of 94 adults were included. Their median age was 33 years; 69 (73.4%) had high-risk and 25 (26.6%) had standard-risk ALL. Of the 94 patients, 67 (71.3%) achieved complete remission (CR), 20 (21.3%) experienced disease resistance, and 7 (7.4%) died early during induction to remission, mainly of sepsis. The 5-year EFS and OS was 23.4% and 31.1% for the whole group and 24.9% and 38.9% for patients who achieved CR, respectively. Of the 94 patients, 50 (43.9%) died of sepsis or disease progression. Relapse developed in 43 patients (45.7%). The median survival after relapse was 6.93 months. Bone marrow was the most frequent site of relapse (21 patients [48.8%]) and conferred a significantly lower 5-year OS of 16.4%. CONCLUSION: Adults with ALL in Mexico had high-risk characteristics and an increased relapse rate; however, the OS after CR was similar to the greatest achieved in developed countries, suggesting that a threshold for curing adult ALL with current therapeutic strategies has been reached.

Cost structure and clinical outcome of a stem cell transplantation program in a developing country: the experience in northeast Mexico.

BACKGROUND AND OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) in developing countries is cost-limited. Our primary goal was to determine the cost structure for the HSCT program model developed over the last decade at our public university hospital and to assess its clinical outcomes. MATERIALS AND METHODS: Adults and children receiving an allogeneic hematopoietic stem cell transplant from January 2010 to February 2011 at our hematology regional reference center were included. Laboratory tests, medical procedures, chemotherapy drugs, other drugs, and hospitalization costs were scrutinized to calculate the total cost for each patient and the median cost for the procedure. Data regarding clinical evolution were incorporated into the analysis. Physician fees are not charged at the institution and therefore were not included. RESULTS: Fifty patients were evaluated over a 1-year period. The total estimated cost for an allogeneic HSCT was $12,504. The two most expensive diseases to allograft were non-Hodgkin lymphoma ($11,760 ± $2,236) for the malignant group and thalassemia ($12,915 ± $5,170) for the nonmalignant group. Acute lymphoblastic leukemia ($11,053 ± 2,817) and acute myeloblastic leukemia ($10,251 ± $1,538) were the most frequent indications for HSCT, with 11 cases each. Median out-of-pocket expenses were $1,605, and 1-year follow-up costs amounted to $1,640, adding up to a total cost of $15,749 for the first year. The most expensive components were drugs and laboratory tests. CONCLUSION: Applying the cost structure described, HSCT is an affordable option for hematological patients living in a developing country.

Chemotherapy alone or HSCT after reduced-intensity conditioning for patients with malignant hematologic diseases are not associated to metabolic syndrome: a cross-sectional observational study.

The relationship between treatment for hematologic malignancies and risk of developing metabolic syndrome (MS) is controversial; in addition, metabolic changes following hematopoietic stem cell transplantation (HSCT) is an area of growing interest. We documented the presence of MS in patients with hematological malignancies treated with chemotherapy and HSCT. Nutritional status, anthropometrics, and pertinent laboratory parameters were used to evaluate the presence of MS using the Adult Treatment Panel (ATP III) criteria. In the study, 115 patients were included. Using ATP III criteria, MS was identified in 42 (44.7%) patients treated only with chemotherapy and in 8 (33.3%) patients with an HSCT. There was an important but not significant difference in the mean fasting glucose, which was higher in the chemotherapy group (108.32 ± 54.28 vs. 94.48 ± 18.25, P = 0.300). Mean values of biochemical markers and blood pressure were not different between the groups. An increase in central obesity in men with hematological diseases in comparison to the rest of the population was also found (46.7% vs 32.4%). There was no difference in the prevalence of MS between patients with hematologic malignancies receiving an HSCT and those treated with chemotherapy alone.

Characteristics and clinical evolution of patients with acute myeloblastic leukemia in northeast Mexico: an eight-year experience at a university hospital.

BACKGROUND/OBJECTIVE: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. We documented the characteristics and results of treatment of patients with AML at a single reference center. METHODS: Patients diagnosed with AML between June 2003 and July 2011 at a university hospital in northeast Mexico were studied. Overall survival (OS) and event-free survival (EFS) were determined, and risk factors were analyzed with respect to their influence on prognosis. RESULTS: A total of 132 AML patients were included. Median age was 32 years. Complete remission (CR) was achieved by 55% of patients. CR was achieved by 65.1% of patients <60 years (n = 109), compared to 8.7% of those >60 years (n = 23; p < 0.001). In all, 39% of patients >60 years suffered an early death, compared to 14.7% of those <60 years (p < 0.001). OS for patients with AML was 35%, whereas EFS was 32%. On multivariate analysis, patients >60 years had a lower OS and EFS (p < 0.001). A total of 28% of patients received a transplant, and they had high er OS and EFS. Conclusions: Our patients were considerably younger and had remarkably lower survival rates than reported for other populations; those >60 years had a higher early death rate, and fewer of these patients achieved CR.

Obesity is associated with higher overall survival in patients undergoing an outpatient reduced-intensity conditioning hematopoietic stem cell transplant.

BACKGROUND: The impact of obesity on hematopoietic stem cell transplantation (HSCT) outcome remains controversial and has been considered a relative contraindication for the procedure. We investigated the influence of Body Mass Index (BMI) on the clinical course of adults undergoing an ambulatory HSCT after a non-myeloablative conditioning regimen. METHODS: Adults with hematologic diseases undergoing an autologous or allogeneic HSCT after reduced intensity conditioning (RIC) and supported exclusively with enteral nutrition (EN) were studied. BMI and body fat were sequentially determined. Patients were divided into three BMI subgroups: underweight; normal, and overweight/obese. RESULTS: Seventy-seven patients with a median follow-up of 21months were evaluated. Fourteen (18.2%) were underweight, 21 (27.3%) had a normal weight, and 42 (54.5%) were overweight/obese. A significant weight loss was observed among all three weight groups after HSCT (P=0.014). No correlation was found between time to engraftment and BMI (P=0.91), serum albumin (P=0.387), and fasting glucose (P=0.64), nor between BMI and acute (P=0.456) or chronic (P=0.209) graft versus host disease (GVHD). On multivariate analysis a higher overall survival (OS) was documented for obese patients (P=0.037). DISCUSSION: A BMI >30/kg/m(2) was independently associated with a higher survival rate after HSCT. Obese patients should not be excluded as transplant candidates based only on this parameter.

Improving acute promyelocytic leukemia (APL) outcome in developing countries through networking, results of the International Consortium on APL.

Thanks to modern treatment with all-trans retinoic acid and chemotherapy, acute promyelocytic leukemia (APL) is now the most curable type of leukemia. However, this progress has not yielded equivalent benefit in developing countries. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) was established to create a network of institutions in developing countries that would exchange experience and data and receive support from well-established US and European cooperative groups. The IC-APL formulated expeditious diagnostic, treatment, and supportive guidelines that were adapted to local circumstances. APL was chosen as a model disease because of the potential impact on improved diagnosis and treatment. The project included 4 national coordinators and reference laboratories, common clinical record forms, 5 subcommittees, and laboratory and data management training programs. In addition, participating institutions held regular virtual and face-to-face meetings. Complete hematological remission was achieved in 153/180 (85%) patients and 27 (15%) died during induction. After a median follow-up of 28 months, the 2-year cumulative incidence of relapse, overall survival (OS), and disease-free survival (DFS) were 4.5%, 80%, and 91%, respectively. The establishment of the IC-APL network resulted in a decrease of almost 50% in early mortality and an improvement in OS of almost 30% compared with historical controls, resulting in OS and DFS similar to those reported in developed countries.

The impact of medical education and networking on the outcome of leukemia treatment in developing countries. The experience of International Consortium on Acute Promyelocytic Leukemia (IC-APL).

OBJECTIVES: Several clinical trials conducted in Europe and US reported favorable outcomes of patients with APL treated with the combination of all trans retinoic acid (ATRA) and anthracyclines. Nevertheless, the results observed in developing countries with the same regimen was poorer, mainly due to high early mortality mainly due bleeding. The International Consortium on Acute Promyelocytic Leukemia (IC-APL) is an initiative of the International Members Committee of the ASH and the project aims to reduce this gap through the establishment of international network, which was launched in Brazil, Mexico and Uruguay. METHODS: The IC-APL treatment protocol is similar to the PETHEMA 2005, but changing idarubicin to daunorubicin. All patients with a suspected diagnosis of APL were immediately started on ATRA, while bone marrow samples were shipped to a national central lab where genetic verification of the diagnosis was performed. The immunofluorescence using an anti-PML antibody allowed a rapid confirmation of the diagnosis and, the importance of supportive measures was reinforced. RESULTS: The interim analysis of 97 patients enrolled in the IC-APL protocol showed that complete remission (CR) rate was 83% and the 2-year overall survival and disease-free survival were 80% and 90%, respectively. Of note, the early mortality rate was reduced to 7.5%. DISCUSSION: The results of IC-APL demonstrate the impact of educational programs and networking on the improvement of the leukemia treatment outcome in developing countries.

Assessment of nutritional status in children with acute lymphoblastic leukemia in Northern México: A 5-year experience.

Nutritional status is an important variable when planning the treatment of children with acute lymphoblastic leukemia (ALL). We determined the nutritional status of children from Northern Mexico diagnosed with ALL during a 5-year period at a public university hospital. One hundred and two children were included. Evaluation by a clinical nutritionist through a food frequency questionnaire and anthropometrical measurements was carried out. Dual energy X-ray absorptiometry (DEXA) for body composition analysis was performed. Based on their body mass index (BMI) percentile, children were classified in four groups as underweight, normal weight, at-risk for overweight and overweight. Fifty-four patients were boys (53%) and 48 (47%) girls. Median values were: age, 6.0 years; weight, 23 kg, height, 118 cm. BMI median value was 16.7. In 78 patients studied by DEXA, median body mass was 24,335 g, with 66.4% from lean tissue, 23.5% from fat. Bone mineral content was 10.6%. Bone density was 0.754 g/cm(2). The majority of children with ALL in Northern Mexico are well nourished at diagnosis and have a normal body composition. Early nutritional intervention is important to maintain this status and correct specific abnormalities.

Successful father-to-son stem cell transplantation in a child with hemophagocytic lymphohistiocytosis using a reduced-intensity conditioning regimen.

OBJECTIVE: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon disorder, usually lethal without allogeneic stem cell transplantation (SCT). MATERIALS AND METHODS: We report a 9-month-old boy, the first child of consanguineous parents, diagnosed with HLH and neurological involvement demonstrated by magnetic resonance imaging (MRI), who received an allogeneic SCT from his HLA genetically matched father. Transplant was performed after a reduced-intensity conditioning (RIC) regimen consisting of cyclophosphamide, fludarabine, and melphalan. Graft vs. host disease (GVHD) prophylaxis included cyclosporine a and methotrexate. RESULTS: An absolute neutrophil count of 0.5 x 10(9)/L was documented on day +20 and a platelet count >20 x 10(9)/L was shown by day 33. Full donor chimerism was showed on day +175. A follow-up brain MRI was reported normal. Twenty months after SCT, the child shows no evidence of HLH or GVHD activity, and has a normal psychomotor development. CONCLUSION: Given the reduced toxicity of SCT with RIC, it could represent an attractive transplant method for children with HLH, in whom myeloablation plays no role in disease eradication, and in whom mixed chimerism may be enough to cure the disease.