Group Of Leukemia Patients Research Articles

Identification of Long Non-Coding RNA Genes Important for Normal Hematopoiesis and Leukemogenesis Using Bioinformatics Tools

Only 1.5% of human genome encodes protein-coding genes, while more than 60% of human genome is transcribed for RNA molecules that have no-protein coding potentials. So far 6,000 long noncoding RNA genes (lncRNA) are documented (Evans et al., 2016). To investigate the functions of lncRNA genes poses huge opportunities as well as challenge to biomedical research. In this project, we interrogate important lncRNA genes that may be associated with normal and abnormal hematopoiesis using publically available databases containing RNA-seq data from different blood lineages and leukemia cells. The data mining and statistical analysis are performed by R program and oracle SQL code. Using RNA-seq data derived from purified blood lineages of human cord blood cells, we have identified long noncoding RNA genes transcribed exclusively in human hematopoietic stem cells as well as in different progenitor lineages. We have discovered two lncRNA genes: linc00028 and As-PP1 are regulated by RUNX1 in hematopoietic stem cells. Given that chromosome translocation t(8;21) generates a fusion protein RUNX1-ETO which often represses genes activated by RUNX1, we proceed to validate whether Linc00028 and As-PP1 may be regulated by transcription factor RUNX1 by chromatin immunoprecipitation assays. Further analysis implies that As-PP1 activated p53-mediated apoptosis via controlling p53 activity. Thus AML1-ETO may repress apoptosis via antagonizing the normal function of RUNX1 in repressing AsPP1 transcription. We have been studying how protein arginine methyltransferases 1 (PRMT1) promotes the progression of acute myeloid leukemia. In this vein, we found that inhibition of PRMT1 activity by small molecule PRMT1 inhibitor upregulated the expression level of the long noncoding RNA gene (As-PP1) and leads to leukemia cell apoptosis. Thus long noncoding RNA genes may serve as biomarkers for PRMT1 inhibitor treatment. By clustering genes of acute myeloid leukemia patients in TCGA database, we found unique lncRNA signature genes specifically associated to distinct groups of leukemia patients with PML-RAR alpha, FLT3 mutation and AML1-ETO (aka RUNX1-ETO) respectively. Whether these signature genes are useful to be applied as biomarkers will be further discussed in the presentation. DisclosuresNo relevant conflicts of interest to declare.

Haploidentical Stem Cell Transplantation with CD3+/CD19+ ex-vivo depletion is a therapeutic option in children without a matched donor, or after graft failure: Experience at the National Institute of Pediatrics

Hematopoietic stem cell transplantation is a widely used therapy for different diseases in the pediatric population. Haploidentical transplantation with negative immunoselection using electromagnetic fields is an alternative for those patients without an HLA-matched donor. Twenty pediatric patients under 18 years old received a haploidentical CD3+/CD19+-depleted transplant due to the absence of an HLA-matched donor. The mean age at which HSCT was performed was 6.6 years (range 1-18 years), and clinical indications were: acute lymphoblastic leukemia (9 patients), primary immunodeficiency (8 patients), acute myeloid leukemia (2 patients), and severe aplastic anemia (1 patient). The medium dose of cells infused was 10.9 (min. 2, max. 32) x 106/kg CD34+ cells, 3.2-4.1 x 105/kg CD3+ cells and 2.4-3.7 x 105/kg CD19+ cells. Results: Eleven of the twenty patients had donor engraftment (55%) and had complete chimera of their donors. From this group, nine (45%) developed primary graft failure, and four (36%) developed graft-versus-host disease. In the group of leukemia patients, overall survival was 75% while event-free survival was 40%. Haploidentical transplantation with negative immunoselection is a useful and feasible strategy for children without an ideal donor. In our cohort, patients with acute leukemia had better outcomes than patients with non-malignant diseases.

Serum lead level in children with acute lymphoblastic leukemia

Introduction: There are some reports where serum lead levels were measured and change in concentration of serum lead level was found among Acute Lymphoblastic Leukemia patients. The aim of this study was to determine serum lead levels in patients with ALL. Methods: In this cross sectional study all children suffering from acute lymphoblastic leukemia ranging 2 to 12 years (30 patients) were evaluated for serum lead levels who were admitted at the Department of Pediatrics in DMCH, from February 2013 to January 2014. Serum measurements for lead were performed by Atomic absorption spectrophotometer in Analytical Chemistry Laboratory of Atomic Energy Centre Ramna, Dhaka. Results: Among the 63 children there was no significant difference in age and sex between the patients and control. The mean serum lead level of Acute lymphoblastic Leukemia patient group (234.8±162.9 g/L) was significantly higher than that of the control group (23.6±12.6 µg/L). There was significant difference of serum lead level in children with ALL and control group(p<0.05). Conclusion: From the findings of the study it can be concluded that there is significant difference between Acute Lymphoblastic Leukemia patient and normal control in terms of serum Lead (pb) level. Key words: Children, Acute Lymphoblastic Leukemia, serum Lead. Journal of Paediatric Surgeons of Bangladesh (2016) Vol. 7 (2): 41-45

Immunoglobulin G Fragment Crystallizable Glycosylation After Hematopoietic Stem Cell Transplantation Is Dissimilar to Donor Profiles.

Immunoglobulin G (IgG) fragment crystallizable (Fc) N-glycosylation has a large influence on the affinity of the antibody for binding to Fcγ-receptors (FcγRs) and C1q protein, thereby influencing immune effector functions. IgG Fc glycosylation is known to be partly regulated by genetics and partly by stimuli in the microenvironment of the B cell. Following allogeneic hematopoietic stem cell transplantation (HSCT), and in the presence of (almost) complete donor chimerism, IgG is expected to be produced by, and glycosylated in, B cells of donor origin. We investigated to what extent IgG glycosylation in patients after transplantation is determined by factors of the donor (genetics) or the recipient (environment). Using an IgG subclass-specific liquid chromatography–mass spectrometry method, we analyzed the plasma/serum IgG Fc glycosylation profiles of 34 pediatric patients pre-HSCT and at 6 and 12 months post-HSCT and compared these to the profiles of their donors and age-matched healthy controls. Patients treated for hematological malignancies as well as for non-malignant hematological diseases showed after transplantation a lower Fc galactosylation than their donors. Especially for the patients treated for leukemia, the post-HSCT Fc glycosylation profiles were more similar to the pre-HSCT recipient profiles than to profiles of the donors. Pre-HSCT, the leukemia patient group showed as distinctive feature a decrease in sialylation and in hybrid-type glycans as compared to healthy controls, which both normalized after transplantation. Our data suggest that IgG Fc glycosylation in children after HSCT does not directly mimic the donor profile, but is rather determined by persisting environmental factors of the host.

Altered brain function in new onset childhood acute lymphoblastic leukemia before chemotherapy: A resting-state fMRI study

ObjectiveCognitive impairments had been reported in childhood acute lymphoblastic leukemia, what caused the impairments needed to be demonstrated, chemotherapy-related or the disease itself. The primary aim of this exploratory investigation was to determine if there were changes in brain function of children with acute lymphoblastic leukemia before chemotherapy. MethodsIn this study, we advanced a measure named regional homogeneity to evaluate the resting-state brain activities, intelligence quotient test was performed at same time. Using regional homogeneity, we first investigated the resting state brain function in patients with new onset childhood acute lymphoblastic leukemia before chemotherapy, healthy children as control. ResultsThe decreased ReHo values were mainly founded in the default mode network and left frontal lobe, bilateral inferior parietal lobule, bilateral temporal lobe, bilateral occipital lobe, precentral gyrus, bilateral cerebellum in the newly diagnosed acute lymphoblastic leukemia patients compared with the healthy control. While in contrast, increased ReHo values were mainly shown in the right frontal lobe (language area), superior frontal gyrus-R, middle frontal gyrus-R and inferior parietal lobule-R for acute lymphoblastic leukemia patients group. There were no significant differences for intelligence quotient measurements between the acute lymphoblastic leukemia patient group and the healthy control in performance intelligence quotient, verbal intelligence quotient, total intelligence quotient. ConclusionThe altered brain functions are associated with cognitive change and language, it is suggested that there may be cognition impairment before the chemotherapy. Regional homogeneity by functional magnetic resonance image is a sensitive way for early detection on brain damage in childhood acute lymphoblastic leukemia.

Current Status of Leukemia Cytotherapy - Exploitation with Immune Cells.

With the development of chemotherapy and hematopoietic stem cell transplantation (HSCT), the prognosis of leukemia patients has been improved greatly in the past few decades. However, relapsed and refractory leukemia is still the major cause of mortality in leukemia patients. Besides, advancing age, poor performance status and severe co-morbidities limit the applicability of cytotoxic chemotherapy in certain groups of leukemia patients. Novel agents including nucleoside analogs, kinase inhibitors targeting oncoproteins and monoclonal antibodies are under investigation for the management of leukemia. Nevertheless, the outcome remains disappointing. Since immune system plays an important role in eradicating tumor cells, a lot of studies have been conducted in the administration of cytotherapy of immune cells as an alternative method when chemotherapy and transplantation fail to cure the disease, including usage of natural killer (NK) cells, cytokine-induced killer (CIK) cells, donor lymphocyte infusion (DLI), chimeric antigen receptor (CAR)-modified T cells, dendritic cell (DC)-based vaccine and antigen-specific cytotoxic T lymphocytes (CTL). Due to overexpression of several leukemia associated antigens (LAA), leukemic cells are potentially suitable for cellular therapy approach. Here we review the recent literature regarding the different types of cytotherapy against leukemia, and talk about both efficacy and adverse effects related to the strategy.

Pentraxin 3 As a Novel Diagnostic and Prognostic Biomarker for Acute GvHD and Fungal Infections in Adult Allogeneic HSCT Recipients

BACKGROUND:Pentraxin 3 (PTX3) is an essential component of the humoral arm of innate immunity, involved in controlling infections and modulating inflammation, and acting as a new prognostic and diagnostic biomarker in these conditions. PTX3 has been recently recognized as an extrinsic oncosuppressor in cancer; its role in hematological malignancies and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is under investigation in both pediatric and adult settings.METHODS:From September 2012 we have conducted a prospective observational study to address the role of PTX3 in 35 adult patients affected by newly diagnosed AML (n=27) or ALL (8), and 73 adult pts who received allo-HSCT for acute leukemia. Stem cell donors were haploidentical (n=45), sibling (n=14), unrelated (n=14). Serial peripheral blood (PB) and bone marrow (BM) samples were collected from all patients. Time-points of sampling for leukemia patients included: diagnosis, relapse, any cycle of chemotherapy (CT; before starting and first day after the end), evaluation of treatment response (including BM), fever (first episode, or clinical suspicion of fungal infection). Samples from allo-HSCT patients were collected as following: before HSCT; at HSCT (day 0); day +7, day +14, 1 month (including BM), 2 months (including BM), 3 months (including BM) and 6 months (including BM) after HSCT; fever (first episode, or clinical suspicion of fungal infection); acute GvHD requiring systemic therapy (at onset or before starting a second line treatment, day+7 of treatment, then weekly during immunosuppressive therapy for 6 weeks). PTX3 level detection was performed with sandwich ELISA (detection limit 0.1 ng/ml).RESULTS:Firstly we analyzed the group of leukemia patients. Although PTX3 levels on PB at leukemia diagnosis were not influenced by patients (age, sex) or disease characteristics (type of leukemia, BM and PB blasts), they correlated with white blood cell counts (p=0,03). No statistical difference was found matching PTX3 levels at diagnosis with disease relapse or overall survival (OS). We did not observe any correlation between PTX3 levels before starting CT and response to treatment.When we moved to examine allo-HSCT patients, we observed an important difference in PTX3 levels on PB at day 0 among patients treated with treosulfan or busulfan-based conditioning (p=0,027). We found a trend towards an increase of PTX3 levels for patients who developed a subsequent GvHD at day +7, and for patients who received ATG instead of PT-Cy at day +14 (p =0,06 for both of them).Moreover, we evaluated 38 events of acute GvHD. Interestingly, PTX3 levels on PB at GvHD onset predict a subsequent evolution to chronic GvHD (p=0,02), also confirmed by ROC analysis (AUC 0.786) which allowed us to identify a threshold of 58 ng/ml (sens 75%, spec 85%). At day +7 from the start of therapy, PTX3 levels were correlated directly with steroid-refractory GvHD (p=0,004) and reflare (p=0,024), and inversely with GvHD resolution (p=0,003). Concomitantly, the ROC analysis identified a threshold of 18 ng/ml as predictor for steroid-resistance (AUC 0,91; sens 75%, spec 85%) and GvHD resolution (AUC 0,848; sens 70%, spec 85%).Finally, we reported 142 infectious events. No difference in PTX3 levels was reported for first and subsequent episodes, or with bloodstream infections. Importantly, in presence of invasive fungal infection (IFI), the levels of PTX3 were significantly increased (p=0,016).CONCLUSIONS:PTX3 is an early biomarker for major transplant-related complications, as IFI and acute GvHD. This study suggests that PTX3 is able to predict GvHD resolution and the risk of subsequent chronic GVHD development; moreover PTX3 predicts steroid-refractory GvHD, offering a new tool in pindividualized clinical management. DisclosuresCiceri:MolMed SpA: Consultancy.

Impact of Social Media on Power Relations of Korean Health Activism

This case study explores how the Korea Leukemia Patient Group (KLPG) uses social media in its internal communication strategy and how that empowers its relationship with external counterparts. This study’s findings indicate that the communication strategy of the local health Non-Governmental Organization (NGO) is changing in response to the increased effectiveness and impact of social media. Using social media (e.g., Twitter) the KLPG can quickly and effectively construct an issue-based advocacy group. Consequently, more legitimacy and representativeness through collected support from the general public have further empowered the KLPG. Yet, the sustainability component in the relationships built through social media use was not evidenced in the current findings. The effects of social media use were analyzed based on data from interviews with top-level KLPG executive members and general members, and from documentation and archival materials. Limitations and suggestions for future research are included.

Intestinal permeability in leukemic patients prior to chemotherapy.

ObjectiveThe objective of this study was to evaluate the intestinal barrier function in leukemia patients before the start of the chemotherapy with an intestinal permeability test using lactulose and mannitol as markers.MethodsThe study enrolled 20 patients diagnosed with leukemia (acute and chronic). Ten healthy volunteers were also submitted to the test as a control group.ResultsThe median lactulose/mannitol ratio was 0.019 for the Leukemia Patient Group, whereas in healthy controls the median was 0.009 (p-value = 0.244). The median lactulose/mannitol ratio in acute leukemia patients was 0.034 giving a p-value of 0.069 when compared to healthy controls. This same comparison was made between acute myeloid leukemia patients and healthy controls with a p-value of 0.149. There was no significant difference in the intestinal permeability between acute and chronic leukemia patients (p-value = 0.098).ConclusionThe intestinal barrier function measured using the intestinal permeability test was similar in leukemic patients overall and healthy controls, but a tendency toward a different pattern was found in the intestinal barrier function of acute leukemia patients.

Elevated expression of pleiotrophin in lymphocytic leukemia CD19+ B cells

Pleiotrophin (PTN) has been demonstrated to be strongly expressed in many fetal tissues, but seldom in healthy adult tissues. While PTN has been reported to be expressed in many types of tumors as well as at high serum concentrations in patients with many types of cancer, to date, there has been no report that PTN is expressed in leukemia, especially in lymphocytic leukemia. We isolated the CD19(+) subset of B cells from peripheral blood from healthy adults, B-cell acute lymphocytic leukemia (B-ALL) patients, and B-cell chronic lymphocytic leukemia (B-CLL) patients and examined these cells for PTN mRNA and protein expression. We used immunocytochemistry, western blotting, and enzyme-linked immunosorbent assay to show that PTN protein is highly expressed in CD19(+) B cells from B-ALL and B-CLL patients, but barely expressed in B cells from healthy adults. We also examined PTN expression at the nucleic acid level using reverse transcription polymerase chain reaction (RT-PCR) and northern blotting and detected a high levels of PTN transcripts in the CD19(+) B cells from both groups of leukemia patients, but very few in the CD19(+) B cells from the healthy controls. Interestingly, the quantity of the PTN transcripts correlated with the severity of disease. Moreover, suppression of PTN activity with an anti-PTN antibody promoted apoptosis of cells from leukemia patients and cell lines SMS-SB and JVM-2. This effect of the anti-PTN antibody suggests that PTN may be a new target for the treatment of lymphocytic leukemia.

Assay of AVP, CRP, and LPS in leukemia

The genesis and development of tumor are closely connected with immune system and neuroendocrine system. To investigate the changes of neuroendocrine and immune system in leukemia patients and their probable connection with leukemia, we studied five groups of patients including leukemia patients with normal temperature, leukemia patients with high temperature and infection (high-leukocyte count group and low leukocyte count group), general patients with fever and healthy Chinese adult blood donors as control group. We determined their blood cell counts by blood count meter, determined their arginine vasopressin (AVP) levels in blood plasma by radioimmunoassay and their cross-reacting protein (CRP), and lipopolysaccharide (LPS) levels by immunoturbidimetry. Then we studied the difference and association among these indexes. Our results revealed a significant increase of AVP, LPS, and CRP levels in the blood of leukemia patients with normal temperature vs. normal people; Individual leukemia patients had high AVP levels although they had normal LPS and CRP levels; In the group of leukemia patients with high temperature and low leukocyte counts, the CRP level is significantly higher than some of other groups, while there was no significant increase in its AVP level. We conclude that no matter the temperature is normal or not, there were always neuroendocrine disturbance, inflammation, and inapparent infection in leukemia patient; To the leukemia patients with low leukocyte counts, the relationship between inflammation and neuroendocrine is more complicated.

Elevated Serum Ras Levels in Patients with LGL Leukemia.

Background: Ras is a GDP/GTP binding G protein that acts as a molecular switch converting signals from the cell membrane to the nucleus to regulate cell proliferation, differentiation, and protein synthesis. Activation of ras oncogenes has been identified in a variety of cancers, including 30% of patients with acute myelogenous leukemia (AML). Large granular lymphocyte (LGL) leukemia is a clonal T-cell lymphoproliferative disorder associated with chronic neutropenia, anemia, or autoimmune diseases, particularly rheumatoid arthritis. The purpose of this study was to evaluate serum ras levels in patients with LGL leukemia.Methods: A novel ras p21 ELISA (Oncogene Science/Bayer HealthCare) employing two monoclonal antibodies was utilized to quantify ras levels in baseline serum obtained from 32 patients with LGL leukemia. A control group of 48 healthy subjects was also used to establish a cutoff for the upper limit of normal for serum ras levels. A 95% non-parametric cut-off was used to determine significant differences in the frequency of elevated serum ras levels in control vs. LGL leukemia patients.Results: The median serum ras level in the 48 healthy control subjects was 125 pg/mL, with a 5% to 95% range of 50–422 pg/mL. The upper limit of normal for serum ras was defined as 422 pg/mL, as determined using the 95 % non-parametric cut-off. In the LGL leukemia patient group, 19 of 32 patients (59 %) had elevated baseline serum ras levels (median 484 pg/mL) (p=0.0001) when utilizing the healthy control upper limit of normal cut-off value.Conclusions: The results of this study indicate that the majority of LGL leukemia patients have significantly elevated serum ras levels when compared to healthy controls. Serum ras should be evaluated as a potential biomarker in larger leukemia trials, especially for response to treatment with inhibitors of the ras signaling pathway.

Elevated serum ras level predicts decreased survival in patients with hematologic malignancies

6562 Background: Ras is a GDP/GTP binding G protein that acts as a molecular switch converting signals from the cell membrane to the nucleus to regulate cell proliferation, differentiation, and protein synthesis. Activation of ras oncogenes has been identified in a variety of cancers, including 30% of acute myelogenous leukemia patients. The purpose of our study was to evaluate serum ras levels and correlate with survival in hematologic cancer patients. Methods: A novel ras p21 ELISA (Oncogene Science/Bayer Diagnostics, Cambridge, MA) employing two monoclonal antibodies reactive with H, K, and N ras was utilized to quantify total ras levels in serum obtained from patients with various hematologic malignancies including acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and chronic lymphocytic leukemia (CLL). Results: The total leukemia patient group consisted of 52 patients. At the 75th percentile serum ras cutpoint (524 pg/ml) 11/52 patients were defined as elevated for serum ras. From this patient group, 38 patients had clinical followup available and were included in the Kaplan-Meier analysis of overall survival. Patients with elevated serum ras (>524 pg/ml) had significantly shorter overall survival compared to those without (median OS 205 vs. 677 days) (p= 0.04). In a multivariate analysis including serum ras level and type of leukemia, serum ras level remained a significant independent variable for shorter overall survival (p=0.004). Within leukemia subtypes 2/18 AML, 4/9 CML, 3/7 ALL, and 0/4 CLL patients had elevated serum ras levels. Conclusions: Leukemia patients with elevated serum ras levels had a significantly shorter overall survival. Serum ras should be evaluated as a potential biomarker in larger leukemia trials, especially for response to treatment with inhibitors of the ras signaling pathway. [Table: see text]

Loss of Heterozygosity and Microsatellite Instability at theMLL Locus Are Common in Childhood Acute Leukemia, but not in Infant Acute Leukemia

Rearrangements involving the MLL gene at chromosome 11q23 are associated with leukemia and are present in up to 70% of infant leukemias. Loss of heterozygosity (LOH) has been shown for anonymous polymorphic markers at 11q23 in adult leukemias. To study LOH at the MLL locus, we have identified two new polymorphic microsatellite markers: a GAA repeat (mllGAAn) in intron 6 of the MLL gene and a GA (mllGAn) repeat in the 5' flanking region of the gene, approximately 2 kb upstream of the translation initiation codon. The heterozygosity index of mllGAAn is 0.54, which renders it useful for analyzing LOH. We screened two groups of leukemia patients to study LOH at the mllGAAn marker. Group A (n = 18) was selected on the basis of presentation before 18 months. Cytogenetic and reverse transcription-polymerase chain reaction analysis showed that 9 of these 18 children had translocations involving MLL. No LOH was observed. Group B (n = 36) were randomly selected children who had presented with leukemia between 1993 and 1994. Cytogenetic analysis of this group showed a variety of different chromosomal abnormalities. LOH was shown in 9 of 20 individuals (45%) who were informative. Microsatellite instability (MSI) was demonstrated in 1 of 18 individuals in group A and 5 of 36 individuals (13.9%) in group B. MSI and LOH were observed simultaneously in three individuals. Loss of an allele was confirmed in one individual by fluorescence in situ hybridization. Individuals with MSI or LOH at mllGAAn were selected for analysis at anonymous polymorphic markers D11S1364 and D11S1356, which flank the MLL gene. No LOH or MSI was observed at these markers in those individuals who were informative. These results show that LOH at the MLL gene locus is a common event during leukemogenesis. Furthermore, the presence of MSI at this locus suggests that the region is a hotspot for genetic instability.

Pattern of neurobehavioral deficits associated with interferon alfa therapy for leukemia

We evaluated the neuropsychological and personality profiles of 25 patients with chronic myelogenous leukemia treated with interferon alfa (IFN-alpha). This group of persons performed well below expectation on tests of cognitive speed, verbal memory, and executive functions. Personality changes included depression, increased somatic concern, and stress reactions. A control group of leukemia patients not treated with IFN-alpha had significantly better cognitive speed and mood. The pattern of cognitive and personality changes in patients receiving IFN-alpha is highly suggestive of frontal-subcortical brain dysfunction.

Invasive fungal disease in pediatric acute leukemia patients with fever and neutropenia during induction chemotherapy: a multivariate analysis of risk factors.

We evaluated the courses of 115 consecutive cases of pediatric acute leukemia treated with induction chemotherapy. Seventy-two patients developed fever associated with neutropenia; 15 developed systemic fungal infections. We reviewed multiple demographic and treatment characteristics of these patients in an attempt to identify potential risk factors for the development of invasive fungal disease (IFD). Risk factors identified in a univariate analysis included duration of neutropenia after first fever (P less than .0001), diagnosis of acute nonlymphocytic leukemia (ANLL) (P = .003), onset of fever and neutropenia within 5 days of starting induction chemotherapy (P = .009), and multiple (greater than one) surveillance culture sites positive for fungal organisms (P = .02). In a multiple logistic regression analysis, duration of neutropenia (P less than .001) remained a significant risk factor. The study group of patients had a significantly higher risk of fungal infections than a matched group of leukemia patients developing fever with neutropenia due to postremission consolidation chemotherapy (P = .003). In the first 48 patients, 14 (29%) developed IFD. In the subsequent patients (n = 24), intravenous miconazole (5 mg/kg every 8 hours) was begun at the time of the first fever. One of the 24 patients (4%) given miconazole developed IFD. The use of miconazole was a negative risk factor for the development of IFD in univariate (P = .01) and multivariate (P = .05) analysis. We conclude that pediatric leukemia patients who develop fever associated with neutropenia during induction chemotherapy are at high risk for developing IFD. The role of intravenous miconazole at the time of the first fever in this group deserves further study.

A phase II study of prednimustine in acute non-lymphocytic leukemia, smouldering leukemia, and refractory anemia with excess blasts.

Prednimustine, an ester of chlorambucil and prednisolone, was evaluated for efficacy and toxicity in a selected group of leukemia patients with a poor prognosis. Disease subsets consisted of patients with acute non-lymphocytic leukemia (ANLL) over age 60; ANLL refractory to standard therapy; smouldering leukemia; and refractory anemia with excess blasts (RAEB). In agreement with previous studies, toxicity from Prednimustine was relatively mild, consisting primarily of infrequent myelosuppression, gastrointestinal side-effects, and mild hyperglycemia. This study did not, however, confirm previously reported remission rates in ANLL: in 41 evaluable patients only two complete remissions were achieved. Both occurred in the subset of patients with smouldering leukemia. We conclude that Prednimustine has limited activity in this patient population.

Leukemia patients to be given varicella vaccine

Varicella vaccine, still experimental in this country, is being used in an effort to protect leukemia patients from potentially fatal chickenpox. The project eventually will involve 500 patients with acute lymphocytic leukemia who never have had chickenpox and lack antibodies to the varicella-zoster virus. An additional group of leukemia patients— those who have survived natural varicella infection without vaccination—are being recruited as controls. The National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Md, which is supporting the study, estimates that up to 7% of immunosuppressed leukemia patients who contract varicella will die. That estimate is largely based on treatment of 77 young cancer patients at St. Jude's Children's Research Hospital, Memphis. Sixty of these patients were immunosuppressed when they developed varicella; four died ( Pediatrics 1975;56:388-397). Among presumably healthy persons, the varicella death-to-case ratio recently in this country has been 6.7/10,000, according to data compiled by Stephen R. Preblud, MD,

Immunocompetence and prognosis in children with acute lymphoblastic leukemia: Combination of two different maintenance therapies

Intensive chemotherapy in patients with leukemia produced immunosuppression. The level of immunocompetence correlates with prognosis. The immunological function of 29 children with acute lymphoblastic leukemia (ALL) in complete remission and on 2 different maintenance therapies was evaluated and compared with 16 normal children (Group A). Sixteen children (Group B) with ALL received 6 mercaptopurine (6MP) daily and methotrexate (MTX) twice a week, and 13 children (Group C) received 6MP and MTX weekly for maintenance. There was depression of both cellular immunity, measured by the number of T cells and skin tests, and humoral immunity, measured by number of B cells, primary antibody production to typhoid vaccine, and levels of immunoglobulins. However, continuous maintenance therapy (Group B) produced significantly more severe immunosuppression of cellular immunity than the intermittent therapy (Group C). Humoral immunity was equally depressed in both groups of leukemia patients, but was less altered than cellular immunity. Concomitantly, patients with intermittent maintenance chemotherapy had less hematologic depression, fewer episodes of infection, and fewer died in complete remission. Patients of both groups with higher levels of immunocompetence had better prognosis with longer duration of complete remission than patients with severe immunosuppression. Out of 6 patients with "favorable immunocompetence" only 1 relapsed at 7 months and the other 5 remain in complete remission from 8 to 31 months. Among 23 leukemic patients with "unfavorable immunocompetence," 15 relapsed and 8 remain in complete remission from 9 to 26 months.

Paper electrophoretic study of serum proteins in children with leukemia

Summary<ul><li>1.Serum protein analyses by paper electrophoresis on twenty-three children with leukemia have been presented.</li><li>2.Normal serum protein patterns were frequently observed. Variations from normal consisted of low albumin and gamma globulin and occasionally an increase in alpha₁ and alpha₂ globulins in patients with acute lymphocytic leukemia. In acute myelogenous leukemia a decrease in the albumin fraction and an increase in alpha₁ and alpha₂ globulins occurred. A low albumin and beta globulin and occasional elevation of the alpha₂ globulin were sometimes seen in patients with chronic myelocytic leukemia. The one patient studied with chronic lymphocytic leukemia showed a normal serum protein pattern.</li><li>3.The mean values for each serum protein constituent in each group of leukemia patients studied fell within the normal range; however, wide variations from the mean plus or minus (±) 1.96 standard deviations of the mean were encountered.</li><li>4.No direct correlation could be made between the alteration of serum protein constituents and the drugs employed in the therapy of these patients except for a decrease in the albumin fraction during steroid therapy.</li><li>5.Alterations in the normal serum protein fractions in patients with leukemia is probably of a nonspecific nature and may be related to tissue destruction, fever, or infection.</li><li>6.Changes in the electrophoretic serum protein components in the present study were of little value in the diagnosis of leukemia; however, the presence of abnormal patterns may lead one to suspect a relapse and progression of the disease.</li></ul>