Anticipation of Relapse and Acute Graft-Versus-Host Disease after Allogeneic Peripheral Blood Stem Cell Transplantation: The Fundamental Role of Antigen-Presenting (Dendritic) Cells.

Background: Dendritic cells (DCs) are antigen-presenting cells. In humans two distinct lineages of DCs exist: DC1 and DC2. Efforts to explore the role of DCs in acute graft-versus-host disease (aGVHD) after allogeneic peripheral blood stem-cell transplantation (PBSCT) are gaining traction. However, further research is needed to identify particular lineages and their values in terms of developing an evidence-based aGVHD- or relapse-prevention strategy. We monitored DC counts and subsets in PBSC grafts while harvesting stem cells in recipients to elucidate their value in anticipating disease relapse or aGVHD. Methods: We enrolled 29 participants. Using fluorescence-activated cell sorting, total counts/kg of CD34+, DCs, and DC subsets were analyzed in 29 PBSC-graft components using CMRF44, CD11c, and CD4 monoclonal antibodies (MoAbs). Results: In the 29 grafts, we detected a significant positive correlation (P<0.01) between DCs and both DC1 and DC2. Significantly higher counts (P<0.01) of DCs and DC1 in those who had developed aGVHD (nine cases) were also observed. Relapsed cases (two) were also associated with higher counts of DCs and DC2. A significant positive correlation (P<0.05), was recorded between DCs and DC1 counts and the day of myeloid engraftment, while this was not detected on the day of platelet engraftment. Myeloid engraftment transpired earlier in patients without aGVHD. Increased DC-graft numbers, particularly DC1 measured by CD11c Moabs, were associated with aGVHD. Recipients of higher numbers of CD4bright DCs had an increased risk of relapse after allogeneic PBSCT. Conclusion: This study analyzed DCs in PBSC grafts, using novel specific MoAbs and flow cytometry. Our data showed that higher donor DC1 counts were linked to the incidence of aGVHD and DC2 with relapse. We propose a fundamental role for DC-graft monitoring in anticipating aGVHD and disease relapse.

Characteristics, Treatment Complexity, and Outcome of Mixed-Phenotype Acute Leukemia in Children in a Low-Middle-Income Country.

Background: Mixed-phenotype acute leukemia (MPAL) in children is an uncommon subtype of acute leukemia that cannot be definitively assigned to a specific lineage. There is no consensus on the best approach to therapy. Management is more complex in low-middle-income countries (LMICs). Aim: To evaluate the clinicopathological characteristics and outcomes of patients with MPAL in a developing country. Patients and Methods: A retrospective descriptive study of 42 pediatric patients newly diagnosed with MPAL from July 2007 until December 2017. Results: The immunophenotyping was T/Myeloid in 24 patients (57.1%) and B/Myeloid in 16 (38.1%). Three subjects had MLL gene rearrangement, two had Philadelphia-positive chromosomes, and eight had FMS-like tyrosine kinase 3 (FLT3-ITD) internal tandem duplication (FLT3-ITD) with a ratio >0.4. Two subjects died before starting chemotherapy. Ten patients (25%) received acute lymphoblastic leukemia (ALL) induction, and all achieved complete remission (CR) with no induction deaths and no shift of therapy. Thirty patients (75%) started therapy with acute myeloid leukemia (AML) induction: five (16.6%) died during induction, 17 (56.7%) achieved CR, and 10 patients received maintenance ALL therapy after ending AML treatment. Four of the eight patients with induction failure were switched to ALL therapy. The 5-year event-free survival (EFS) and overall survival (OS) rates were 56.7% [standard error (SE): 8.1%] and 61% (SE: 8%), while the cumulative incidence of relapse was 21.7% (SE: 6.7%), with a median follow-up duration of 5.8 years. Patients treated with ALL-directed therapy had a 5-year EFS rate of 111 70% (SE: 14%) and OS rate of 78.8% (SE: 13%). Patients treated with ALL-directed therapy had a 5-year EFS rate of 70% (SE: 14.5%) and OS rate of 78.8% (SE: 13%). FLT3-ITD mutation showed a significantly lower 5-year EFS rate of 28.6% (SE: 17%) vs. 75% (SE: 9%) for the wild type, p = 0.032. Undernourished patients with a body mass index (BMI) z-score ≤-2 at presentation had a significantly lower 5-year EFS rate of 20% (SE: 17%) compared to 61.8% (SE: 8%) for patients with BMI z-score >-2, p = 0.015. Conclusion: This study supports ALL-directed therapy for pediatric MPAL in a setting of LMIC. Given the poor outcome of FLT3-ITD, the role of FLT3 inhibitor needs to be explored in this subset of cases.

HBVsvp-Pulsed Dendritic Cell Immunotherapy Induces Th1 Polarization and Hepatitis B Virus-Specific Cytotoxic T Lymphocytes Production.

BACKGROUND: In chronic hepatitis B virus (CHB) patients, both dendritic cells (DCs) and T cells are functionally impaired and consequently the HBV-specific cellular immune responses are downregulated. The present study aims to investigate whether monocyte-derived DC (MoDCs)-pulsed-HBV subviral particles (HBVsvp) can polarize Th1 cells to induce HBV-specific cytotoxic T-lymphocytes (CTL) responses in CHB patients. METHODS AND MATERIALS: To this end, the human hepatoma HepG2.2.15 cell line was used to produce HBVsvp as a culturing system, and HBVsvp were concentrated for highly virus titer using the polyethylene glycol protocol. Peripheral blood mononuclear cells (PBMCs), collected from CHB patients and healthy donors, were differentiated into MoDCs and T cells. PBMCs-derived MoDCs were first pulsed with HBVsvp and then cultured with PBMCs-derived T cells. MoDCs and/or T subsets cells were identified for phenotypic activation by FACS analysis. The cytokine secretion of IL-4, IL-12, and IFN-γ in the culture supernatants was detected. RESULTS: The MoDCs were restored for their activation upon pulsing with HBVsvp in vitro, as identified by significantly overexpression of both CD86 and HLA-DR, and overproduction of IL-4 and IL-12. Furthermore, MoDCs-pulsed-HBVsvp induced Th1 frequencies and activated HBV-specific CTL to produce significantly highest amount of IFN-γ. Enhanced HBV-specific CTL led to strong cytolytic capacity against HepG2.2.15. CONCLUSION: Overall, our data suggest that in vitro activation of MoDCs with HBVsvp overcomes the functionally impaired DCs and T cells in CHB patients offering a promising tool for therapeutic or vaccine-based approaches against HBV.

Tracing Leukemia Stem Cells and Their Influence on Clinical Course of Adult Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) evolves from neoplastic transformation of stem cell disease termed "leukemia stem cells" (LSCs). An unsatisfactory response to AML therapy is determined by the presence of minimal residual disease (MRD). The predominance of LSCs might anticipate sustained MRD results. The present study aimed to demonstrate the effect of LSCs on MRD at induction days 14 and 28 on overall survival (OS) and disease-free survival (DFS) and to compare LSC expression with MRD status. PATIENTS AND METHODS: A total of 84 patients with de novo adult AML underwent testing using LSC panels for CD38/CD123/CD34/CD45 and CD90/CD133/CD45/CD33 and different regular MRD panels. RESULTS: At day 14 after induction, the high expression of CD123 and CD133 had adverse effects on both OS and DFS (P = .004 and P ≤ .001 and P ≤ .001 and P ≤ .001, respectively). Greater expression of CD34+/CD38-/CD123+ resulted in unfavorable OS and DFS (P ≤ .001 for both). Both CD34+/CD38-/CD123+ and CD34-/CD38+/CD123+ expression at day 14 after induction had an adverse effect on DFS only (P < .001 and P = .029, respectively). On multivariate analysis, CD133 expression and MRD status were independent prognostic parameters (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.2-4.4; P = .015; and HR, 2.9; 95% CI, 1.0-7.9; P = .041). At day 28 after induction, MRD and increased CD123+/CD34-, CD34+/CD38-/CD123+, CD133+/CD33- expression were associated with inferior OS (P = .016, P = .0035, P = .0.002, and P = .002, respectively). MRD and high expression of CD34+CD123+, CD133+/CD33-, CD34+/CD38-/CD123+ were associated with inferior DFS (P < .001, P = .002, P < .001, P < .001, respectively). On multivariate analysis, only CD133+/CD33- expression was the independent prognostic factor (HR, 3.1; 95% CI, 1.5-6.7; P = .003). CONCLUSIONS: Estimation of LSC expression is a sensitive indicator of the response to therapy in adult patients with AML and might be a better prognosticator than the findings from regular MRD panels.

Increased expression of brother of the regulator of imprinted sites in peripheral blood neutrophils is associated with both benign and malignant breast lesions.

BACKGROUND: BORIS, a paralog of the multifunctional CCCTC-binding factor (CTCF) gene is restricted to testis and normally not present in females. It is aberrantly activated in various human cancers including cancer breast. Using immunohistochemistry, western blot and/or RT-PCR, significantly higher levels of BORIS expression were reported in the neutrophils of cancer breast patients. We hypothesized that Flow Cytometry might be a better technique for objective quantitative evaluation of BORIS in neutrophils and we wanted to investigate if BORIS would discriminate between benign and malignant breast lesions. METHODS: The study included 85 females; 52 breast cancer, 13 benign breast lesions and 20 age-matched healthy controls. BORIS expression in the neutrophils was detected by Flow Cytometry. RESULTS: High level of BORIS was detected in all malignant (64.4 ± 16.6%) and benign cases (67 ± 12.3), mean florescent intensity ratio (MFIR) of 7.2 ± 4.1 and 7 ± 3.5, median 5.8 and 6.6%; and staining index (SI) 8.3 ± 3.9 and 8.2 ± 3.4, median 7.6 and 7.9 respectively vs.13.4 ± 11.5% MFI 1.8 ± 0.7, median1.6 and SI 2.6 ± 0.69, median 2.5 for the control. BORIS level was comparable in the malignant and benign group (P = 0.934) and significantly higher than control (P = 0.0001). There was no correlation between neutrophil BORIS expression and ER/PR status, HER-2/neu expression or tumor stage or size. CONCLUSIONS: Increased BORIS expression in peripheral blood neutrophils is associated with both benign and malignant breast lesions; apparently, increased proliferation of breast tissue is the determining factor. This excludes BORIS as a tumor marker but it does not jeopardize its value as a potential therapeutic target. © 2016 International Clinical Cytometry Society.

Adhesion molecules expression in CLL: Potential impact on clinical and hematological parameters.

BACKGROUND: B-cell chronic lymphocytic leukemia (CLL) is marked by the accumulation of CD5+ B lymphocytes within the blood, bone marrow (BM), and secondary lymphoid tissues. Abnormalities in the expression and function of cell adhesion molecules may account for the patterns of intra-nodal growth and hematogenous spread of the malignant cells. Chemokines and integrin-mediated adhesion and trans-endothelial migration (TEM) are central aspects in trafficking and retention of hematopoietic cells in the BM and lymphoid organs. AIM OF THE WORK: This work was conducted to study adhesion molecules status in CLL and its potential impact on both hematological and clinical parameters. PATIENTS AND METHODS: The study included 78 newly diagnosed CLL patients. Immunophenotyping was performed on peripheral blood using the chronic lymphoid panel. Adhesion molecules (CD11a, CD11b, CD49d, CD49C, CD29 and CD38) were tested using monoclonal antibodies and analyzed by Flow Cytometry. RESULTS: Positive correlation was encountered between adhesion molecules: CD38 with CD49d (r=0.25, p=0.028), CD11a with CD11b, CD49d and CD29 (r=0.394, p=0.001; r=0.441, p=<0.01 and r=0.446, p<0.01 respectively) and CD29 with CD49c and CD49d (r=0.437, p<0.01; r=0.674, p<0.01 respectively). CD49c showed negative correlation with Rai staging (r=-0.269, p=0.033). CD11a and CD29 showed a significant relation with splenomegaly (p=0.04 and 0.03 respectively) and CD49d showed a significant relation with lymphadenopathy (p=0.02). CONCLUSION: The level of different adhesion molecules expression in CLL is apparently reflected on the potential migratory behavior of the leukemic cells to different organs.

The prognostic significance of minimal residual disease in adult Egyptian patients with precursor acute lymphoblastic leukemia.

BACKGROUND: Minimal residual disease (MRD) studies in adult acute lymphoblastic leukemia (ALL) give highly significant prognostic information superior to other standard criteria as age, gender and total leucocytic count (TLC) in distinguishing patients at high and low risk of relapse. OBJECTIVES: We aimed to determine the value of MRD monitoring by flowcytometry (FCM) in predicting outcome in adult Precursor ALL patients. PATIENTS AND METHODS: Bone marrow (BM) samples were analyzed by 4-color FCM collected at diagnosis and after induction therapy (MRD1) to correlate MRD positivity with disease free survival (DFS) and overall survival (OS). RESULTS: Study included 57 adult ALL patients (44 males and 13 females) with a median age of 22 years (18-49). DFS showed no significant difference with age, gender and initial TLC (p=0.838, 0.888 and 0.743, respectively). Cumulative DFS at 2 years was 34% for B-lineage ALL (n: 35) and 57% for T-lineage ALL (n: 18) (p = 0.057). Cumulative DFS at 2 years was 7% for MRD1 positive (high risk, HR) versus 57% for MRD1 negative patients (Low risk, LR) (p < 0.001). Cumulative DFS at 2 years was 29% for HR patients (n: 26) versus 55% for LR (n: 27) according to GMALL classification (p = 0.064). Cumulative OS did not differ according to age, gender and TLC (p = 0.526, 0.594 and 0.513, respectively). Cumulative OS at 2 years was 36% for B ALL (n: 39) versus 77% for TALL (n: 18) (p = 0.016) and was 49% for Philadelphia chromosome (Ph) negative patients versus 0% for Ph-positive patients (p < 0.001). Regarding MRD1, OS at 2 years was 18% for MRD1 HR (n: 17) versus 65% for MRD1 LR (n: 38) (p < 0.001). OS was 35% for high-risk patients (n: 30) and 62% for low-risk patients (n: 27) classified according to GMALL risk stratification (p = 0.017). CONCLUSION: MRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients.

Induction and repair of DNA double-strand breaks using constant-field gel electrophoresis and apoptosis as predictive markers for sensitivity of cancer cells to cisplatin.

This study was designed to evaluate some parameters that may play a role in the prediction of cancer cells sensitivity to cisplatin (CIS). Sensitivity, induction and repair of DNA double-strand breaks (DSB), cell cycle regulation and induction of apoptosis were measured in four cancer cell lines with different sensitivities to CIS. Using a sulphorhodamine-B assay, the cervical carcinoma cells (HeLa) were found to be the most sensitive to CIS followed by breast carcinoma cells (MCF-7) and liver carcinoma cells (HepG2). Colon carcinoma HCT116 cells were the most resistant. As measured by constant-field gel electrophoresis (CFGE), DSB induction, but not residual DSB exhibited a significant correlation with the sensitivity of cells to CIS. Flow cytometric DNA ploidy analysis revealed that 67% of HeLa cells and 10% of MCF-7 cells shift to sub-G1 phase after incubation with CIS. Additionally, CIS induced the arrest of MCF-7 cells in S-phase and the arrest of HepG2 and HCT116 cells in both S phase and G2/M phase. Determination of the Fas-L level and Caspase-9 activity indicated that CIS-induced apoptosis results from the mitochondrial (intrinsic) pathway. These results, if confirmed using clinical samples, indicate that the induction of DNA DSB as measured by CFGE and the induction of apoptosis should be considered, along with other predictive markers, in future clinical trials to develop predictive assays for platinum -based therapy.

Flow cytometric platelet cross-matching to predict platelet transfusion in acute leukemia.

A great variety of patient- and product-related factors influence the outcome of platelet transfusions. Our study assessed the predictive value of a flow cytometric platelet cross match test for the outcome of HLA matched and unmatched platelet transfusions in patients with acute leukemia. Thirty nine patients (26 adults and 13 children) received 60 ABO compatible apheresis platelet unites ranging from 1 to 4 per patient (mean = 1.54; median = 2). We performed flowcytometric platelet cross-matching, HLA Class I typing by sequence-specific primer (SSP) for patients and complement-dependent cytotoxicity (CDC) for donors and screening of HLA Class I antibodies by ELISA. Effectiveness of platelet transfusion was evaluated using the corrected count increment which was calculated at 60 min and 18- to 24-h posttransfusion. Multivariate analysis was performed to detect which variable can predict transfusion response more than others. Cross-matched platelet transfusions associated with good response in 51.4% of transfusion events in adults and 73.3% in children. The noncrossmatched platelet transfusions associated with poor response in 83.3% in adults and 100% in children (P-values 0.143, 0.041, respectively). In the presence of clinical factors or HLA alloimmunization in adults, cross-matched platelets were associated with good response in 29.6 and 22.2% respectively. In children this occurred in 81.8 and 66.7%, respectively. In presence or absence of HLA matching, flow cytometry platelet cross-matching was the most predictor for transfusion response (P = 0.05). Because of the difficulties to find frequent HLA matched donors for acute leukemia patients; flow cytometric platelet cross-matching may provide the most useful way for selecting donors. It is useful even in the presence of alloimunization in children.

Prevalence of anti human herpes virus-6 IgG and its receptor in acute leukemia (membrane cofactor protein: MCP, CD46).

BACKGROUND: CD46 is a membrane cofactor protein, which acts as a cofactor for factor I proteolytic cleavage of C3, so it protects the cells expressing it on their surface from autologous complement attack. It has been recently described as a receptor for HHV-6. Also, it has been shown to be highly expressed on malignant cells as compared to normal cells, thus playing a major role by which these cells, either cells of haematological malignancy or cells of other body cancers, can protect themselves against complement attack so they can survive and metastasize. PATIENTS AND METHODS: This study has been done to detect the seroprevalence of HHV-6 among 47 Egyptian adult cases of acute leukemia using the anti-HHV-6 IgG ELISA serological technique. CD46 receptor expression and immunophenotyping technique were performed using FCM. Twenty nine of the cases were ANLL, while 18 were ALL cases. Sixteen age- and sex-matched control cases were also studied for both anti-HHV-6 IgG and CD46 receptor expression. RESULTS: HHV-6 IgG antibodies were encountered in 29 (100%), 14 (77.8%) and 12 (75%) of the ANLL, ALL and the control group, cases, respectively. CD46 expression was encountered in 21 (72.4%) of the ANLL cases and in 10 (55.6%) of the ALL cases. Concordance between HHV- 6 seropositivity and CD46 expression was encountered in 31 cases (29 positive and 2 negative). Disconcordance was encountered in 16 cases with 14 showing HHV-6 IgG seropositivity with no CD46 expression and 2 showing the reverse. CONCLUSION: The lack of significant correlation between CD46 expression and seropositivity would exclude CD46 expression as a cause of contracting HHV-6 infection in leukemic patients.

Modulation of epirubicin cytotoxicity by tamoxifen in human breast cancer cell lines.

The present study was designed to investigate the modulatory effect of the anti-estrogen, tamoxifen (Tam) on epirubicin (Epi) cytotoxicity in breast cancer cell lines; MCF-7 and NCI-adr. Using sulphorhodamine-B assay, NCI-adr cell line was found to be five-folds more resistant to the cytotoxic effect of Epi as compared to MCF-7 cell line. Pretreatment of cells with Tam was observed to enhance Epi cytotoxicity by 4.3- and 6.5-folds in MCF-7 and NCI-adr cells, respectively. Tam-Epi interaction was found to be additive in MCF-7 cells and synergistic in NCI-adr cells. Flowcytometric DNA ploidy analysis revealed that, Epi induced cell arrest at G2/M phase. Tam pretreatment enhanced the blocking activity of low dose of Epi in MCF-7 and induced nearly two-fold increase in the percentage of S phase in NCI-adr cells. Determination of cellular Epi level revealed that Tam induced a significant increase in intracellular Epi accumulation only in NCI-adr cells after 48 h. However, analysis of P-gp function revealed that Tam failed to modulate P-gp function in both cell lines. Also, assessment of topoisomerae IIalpha gene expression showed that neither Epi nor Tam managed to change its expression level. In conclusion, Tam potentiates Epi cytotoxicity in sensitive and resistant breast cancer cell lines. This potentiation can be explained by an enhancement of cell accumulation in S and G2/M phase, at which the cells are most sensitive to the cytotoxic effect of Epi as well as an increase in the intracellular level of Epi in resistant cell line.

P-gp expression and Rh 123 efflux assay have no impact on survival in Egyptian pediatric acute lymphoblastic leukemia patients.

PURPOSE: In a previous work we have studied MDR status in terms of P-glycoprotein (P-gp) expression and Rhodamine 123 efflux assay in Egyptian acute leukemia patients. We have reported results comparable to the literature as regards ANLL both in pediatric and adult cases. However, higher figures were encountered for the functional assay in ALL. As our ALL cases especially in pediatric age group show worse prognosis compared to literature, we hypothesized that the higher percentage of cases with positive Rh123 efflux assay might be a contributing factor. MATERIAL AND METHODS: A total of 108 cases were studied including 80 ALL and 28 ANLL. ALL cases included 48 male and 32 female with an age range of 6m to 18 yrs and a median of 7 yrs. ANLL cases included 18 male and 10 female with an age range of 6m to 18 yrs and a median of 8 yrs. P-gp expression was evaluated using 4E3 and UIC2 mAb, analyzed by Coulter XL flow cytometer and expressed as a ratio at a cut off of >or= 1.1 and/or >or= 5% positive cells. For the evaluation of MDR function Rh123 efflux assay using cyclosporine as a blocker and expressed as a ratio at a cutoff of >or= 1.1 and/or >or= 10% positive cells was performed. MDR expression and function were correlated to age, Hb, TLC, CD34 expression, immunophenotype and DNA index in ALL, FAB subtypes in ANLL as well as to CR, DFS and EFS in ALL. RESULTS: In ALL, P-gp expression was encountered in 26.4% of cases. Positive Rh efflux was reported in 61.5%. No correlation was encountered between neither expression nor functional assay with age, Hb, TLC, CD34 expression or immunophenotype. CR was achieved in 89.8%; neither P-gp expression nor Rh123 efflux had an impact on CR except for Rh123 efflux in T-ALL where a cutoff of 1.25 could predict CR at a total accuracy of 70.6%. DFS was 92.3% while EFS was 72.2% for the whole group. No significant difference was encountered neither between cases expressing or lacking P-gp nor between cases with negative or positive Rh123 efflux assay. In ANLL P-gp expression was encountered in 47.6% of cases, while positive Rh123 efflux assay was encountered in 75% of cases. No correlation as encountered between neither expression nor Rh123 efflux assay and neither age, Hb, TLC, CD34 expression nor FAB subtypes. CONCLUSION: Neither P-gp expression nor Rh123 efflux assay has any impact on survival in pediatric ALL. Rh123 ratio of 1.25 is predictive of CR in TALL.

Outcome and prognostic factors of acute lymphoblastic leukemia in children at the National Cancer Institute, Egypt.

OBJECTIVE: To improve survival of children with acute lymphoblastic leukemia (ALL) in the authors' institute and to define significant prognostic factors. METHODS: This study included 154 children with newly diagnosed ALL below the age of 18 years during the period August 1, 1998, to December 31, 2000. All patients were treated according to the NCI, Cairo, Egypt, treatment protocol modified from study XIII for high-risk ALL of St. Jude Children's Research Hospital. RESULTS: B-cell precursor phenotype was encountered in 73.4% of patients, T-cell in 26.6%. According to NCI/Rome criteria for risk classification, 58.4% of patients were in the high-risk group (90% of T-lineage compared with 47% of B-lineage ALL, P < 0.001). Nine patients (5.8%) died during induction and 10 patients (6.5%) failed to achieve remission. With a median follow-up of 43 months, the 3-year disease-free survival and its probability at 5 years were 80 +/- 3.6% and 75.3 +/- 4%, respectively; the 3-year event-free survival and its probability at 5 years were 69 +/- 3.8% and 65.2 +/- 4%, respectively. B-cell precursor ALL had 5-year probabilities of disease-free survival and event-free survival of 80.5 +/- 4% and 71.8 +/- 4.5% compared with 60.2 +/- 8.6% and 46.7 +/- 8% for T-cell, respectively (P < 0.01, log-rank test). Prognostic factors that had a statistically significant unfavorable impact on survival by univariate analysis were age 10 years or more, central nervous system involvement, T-lineage phenotype, high-risk group, DNA index less than 1.16, and slow early response to treatment. By multivariate analysis, central nervous system involvement, high-risk group, and slow early response to treatment still had prognostic significance. Risk classification demonstrated prognostic significance for B-lineage but not T-lineage ALL. CONCLUSIONS: This treatment protocol was effective in improving ALL survival among patients at the authors' institute compared with previous trials, although the outcome remains lower than that in more industrialized countries. Prognostic factors defined in this study were similar to those identified by other cooperative groups.

The potential palliative role and possible immune modulatory effects of low-dose total body irradiation in relapsed or chemo-resistant non-Hodgkin's lymphoma.

In a group of 35 patients with relapsed and/or chemo-resistant non-Hodgkin's lymphoma (NHL), low-dose total body irradiation (LTBI) (+involved-field radiotherapy to bulky sites) achieved a complete remission rate of 29%, 2-years progression-free survival of 32% and a median progression-free survival of 12 months. The 2-year survival was 42% and the median survival was 17 months. Immuno-staining and flow cytometry of peripheral blood in 14 patients showed that LTBI leads to a significant increase in the percentage of CD4+ cells with a consequent significant increase in the CD4+/CD8+ ratio. High lymphocytic percent and a high percentage of CD4+ cells before LTBI were significantly correlated with longer response duration and overall survival. These data may suggest that the palliative potential of LTBI should be investigated as an alternative to chemotherapy in NHL patients. The pre-treatment percentage of lymphocytes and CD4+ cells may be used as predictors for response to LTBI.