Search

We aimed to evaluate care for leukemia and lymphoma patients during their last hospitalization from the perspective of the bereaved family. Questionnaires were sent to the bereaved family members of adult leukemia and lymphoma patients. We used the Care Evaluation Scale (CES) and asked the bereaved family members about care satisfaction and "good death" factors during the patient's last week of life or last admission period. We distributed 177 questionnaires and were able to analyze 103 (58.2%) responses. Compared with the results of a previous study of palliative care units in Japan, the CES scores were significantly lower in 9 out of 10 domains. Assessment of the "good death" components revealed that only 33% of respondents agreed that the patient had been relieved as far as possible of pain and physical distress during the last week of life. Only 21.4% of respondents agreed that the patient had been relieved as far as possible of psychological distress, and 57% of caregivers were not satisfied with the level of care. During the last hospitalizations of leukemia or lymphoma patients, their care was insufficient and a good death was not often achieved. Improvement of end-of-life care for leukemia and lymphoma patients is needed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The TARGET system is an online database that can be easily accessed by physicians. The registration of one's own chronic myeloid leukemia (CML) patients in the TARGET system makes it possible to share experiences among physicians, and, thus, may facilitate appropriate treatment for patients. Patients were registered in the TARGET system from October 2003 to March 2010 in Japan. A total of 1236 patients from 176 hospitals were registered in Japan. We analyzed data from 639 CML chronic phase patients not receiving prior therapy registered in this system. After 90 months follow-up, high survival rates were demonstrated for imatinib-treated newly diagnosed CML patients, with event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) rates of 79.1, 94.8, and 95.1%, respectively. A landmark analysis of 296 patients who showed a complete cytogenetic response (CCyR) at 12 months after the initiation of imatinib treatment revealed that, at 90 months, 99% of patients (95% CI, 98-100) had not progressed to accelerated phase (AP) or blastic crisis (BC). The patients showing a CCyR and a reduction of at least 3log levels of BCR-ABL transcripts after 18 months of treatment had an estimated survival rate without CML progression of 100% at 84 months. The probability of achieving undetectable BCR-ABL in patients by 72 months with an major molecular response (MMR) at 12 months was 86.5%, compared with 64.7% for those without an MMR (p < 0.0001). There were no new safety issues. In summary, based on this 7-year TARGET analysis, imatinib showed a continual clinical benefit as first-line therapy for newly diagnosed CML. The TARGET system may represent a more practical and general feature compared with the IRIS study., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Aggressive natural killer cell leukemia (ANKL) is an intractable malignancy that is characterized by the outgrowth of NK cells. To identify transforming genes in ANKL, we constructed a retroviral cDNA expression library from an ANKL cell line KHYG-1. Infection of 3T3 cells with recombinant retroviruses yielded 33 transformed foci. Nucleotide sequencing of the DNA inserts recovered from these foci revealed that 31 of them encoded KRAS2 with a glycine-to-alanine mutation at codon 12. Mutation-specific PCR analysis indicated that the KRAS mutation was present only in KHYG-1 cells, not in another ANKL cell line or in clinical specimens (n=8).

We found that the ratio of CD4(+) to CD8(+) T cells (CD4/CD8 ratio) was decreased in patients with multiple myeloma (MM) and that this decrease was significantly related to an increase of human leukocyte antigen (HLA)-DR expression by CD8(+) (but not CD4(+)) T cells (P<0.005). In addition, the serum level of interleukin (IL)-16 was significantly higher in stage III MM patients than in healthy controls (P<0.001). The decrease of CD4(+) T cells in MM may be mediated by activation of CD8(+) T cells derived cytokine IL-16. In addition, these T cell phenotypic changes and the IL-16 level appear to be useful indicators of disease activity.

Adhesive ligands on acute myeloid leukemic (AML) blasts may mediate transmigration and extravascular infiltration. In this study, 30 AML samples were examined for expression and density of adhesion antigens. By univariate analysis, four patients with extravascular infiltration showed significantly higher expression of CD2, CD11a, CD11b, CD11c, CD15, CD65, CD86, and HLA-DR as compared with patients without infiltration. These four patients also showed significantly higher density of CD11a, CD11b, CD11c, CD15 and CD65 expression. By multivariate analysis, CD65 expression was the only significant independent risk factor for infiltration, suggesting that this is a critical adhesion molecule for extravascular AML infiltration.

We performed immunocytochemistry to detect mdr1 and mdr3 P-glycoproteins (P-gps) in 81 patients with acute and chronic leukemia, using the mdr1 P-gp-specific monoclonal antibody (MoAb) MRK16, and the mdr3 P-gp-specific MDR3M. Immunoreactivity for the mdr1 gene product was positive in 27 out of 81 (33%) patients. Immunoreactivity with the anti-mdr3 P-gp MoAb was positive in 20 out of 81 (25%) patients. Of 54 patients with acute leukemia, 17 (31%) were positive for mdr1 P-gp and 8 (15%) for mdr3 P-gp. A high proportion (60%) of patients with chronic lymphocytic leukemia (CLL) were mdr3 P-gp positive. Of the patients with granular-lymphocyte proliferative disorder (GLPD), a chronic T-cell or natural killer cell leukemia, 8/17 (47%) were positive for mdr1 P-gp and 6/17 (35%) for mdr3 P-gp. Of 23 patients with chronic leukemia (CLL and GLPD), 10 (37%) were positive for mdr1 P-gp and 12 (44%) for mdr3 P-gp. To clarify the function of the mdr3 P-gp, we examined the intracellular rhodamine123 (Rh123) levels of mdr1 P-gp-negative and mdr3 P-gp-positive leukemic cells from patients with acute lymphocytic leukaemia, on the addition of 10 microM cyclosporin A (CyA). The addition of CyA led to significant increases in intracellular Rh123 levels in mdr1 P-gp-negative and mdr3 P-gp-positive leukemic cells. Results of the assay for dye efflux suggested that the mdr3 P-gp has a role in drug resistance, and functional drug-efflux capacity. In 31 acute leukemia patients at initial diagnosis, mdr1 or mdr3 P-gp expression correlated significantly to an outcome of complete remission (CR). In 54 acute leukemia patients, exposure to precytotoxic agents correlated significantly to expression, with a significant higher number of patients mdr1 or mdr3 P-gp positive than negative. In the 54 patients with acute leukemia, mdr1 P-gp expression correlated to mdr3 P-gp expression significantly (p=0.0007). In the 27 patients with chronic leukemia (CLL and GLPD), mdr1 and mdr3 P-gp expression did not correlate to exposure to precytotoxic agents, nor did mdr1 P-gp expression correlate to mdr3 P-gp expression. It may be speculated that precytotoxic agents induced mdr1 and mdr3 P-gp expression in acute leukemia; however, in chronic leukemia, both P-gps were expressed independently of exposure to precytotoxic agents.

We analysed p53 mutations in 24 patients with myelodysplastic syndrome (MDS) and overt acute myeloid leukaemia after a period of MDS, using polymerase chain reaction-single strand conformation polymorphism analysis. In exons 5 to 8, mobility shifts were detected in five of the 24 patients. Sequence analysis was subsequently performed, and four missense mutations (16.7%) and one silent nucleotide substitution were identified. Patients harbouring mutations were characterized as having advanced disease. Loss of the wild type allele was observed in three of the four patients with missense mutations. No mobility shifts of the N-ras or FMS gene were detected in these four patients. We next analysed the correlation of the p53 mutations with the progression of MDS in three patients. The mutation was accompanied by the progression in two of the three patients. These findings suggest that mutations of the p53 gene are associated with progression in some cases of MDS, while being compatible with stable disease or clonal evolution in others.

The effects of leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) on blast progenitors from acute myeloblastic leukemia (AML) were examined using a blast colony assay in a serum-free culture system. LIF and IL-6 stimulated colony growth in 2 and 5, respectively, of 11 cases studied. The simultaneous addition of LIF with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3) or IL-6 produced a statistically significant increase of colony numbers in 3, 6 and 7 of 11 cases, respectively. Numbers of colonies increased significantly when IL-6 was added simultaneously with GM-CSF or IL-3 in 5 and 4 of 11 cases, respectively. LIF or IL-6 used in the primary culture did not significantly change the numbers of secondary colonies compared to GM-CSF. Previous exposure to LIF and IL-6 did not alter cellular phenotype or morphology, indicating that LIF and IL-6 did not induce the differentiation of fresh AML blasts.

The cell surface markers on the leukemic cells of 76 patients with adult acute myeloid leukemia (AML) have been analyzed by indirect immunofluorescence, and the presence of CD56+ leukemic cells was detected in ten of these patients. Four of these 10 CD56+ AML patients developed extramedullary myeloblastomas and in two of them an intracranial myeloblastoma. In contrast, in the remaining 66 CD56- AML patients, only one patient developed a myeloblastoma formation of the subcutaneous. It may be that the CD56 antigen which is an isoform of the neural cell adhesion molecule (NCAM), expressed on neurons, satellite cells of skeletal muscle cells, and on stromal cells, binds these tissues by a homophilic mechanism. CD56+ leukemic cells are capable of invading and of surviving in extramedullary tissues, where they proliferate and develop into a myeloblastoma. Because of this possibility, CD56+ AML patients should be carefully monitored for signs of myeloblastoma formation.

We investigated the proliferative effects of interleukins 1-7 (IL-1 to -7) on leukemic cells from 10 patients with T-lineage acute lymphoblastic leukemia (T-ALL). Five patients had CD7+4-8-acute leukemia, one had CD5+ acute leukemia, and four had CD1+ acute leukemia. To examine the proliferative effect of each interleukin, 3H-TdR incorporation method was used. In the presence of IL-1, no increase in 3H-TdR incorporation was observed for any of the T-ALL cells. With IL-2, 3H-TdR incorporation increased in cells from 5 out of 10 T-ALL patients, including those with CD7+4-8-, CD5+, and CD1+ acute leukemia. In the presence of IL-3 or IL-6, 3H-TdR incorporation increased in cells from 2 out of 5 patients with CD7+4-8- acute leukemia. However, CD5+ or CD1+ acute leukemia cells were not stimulated by IL-3 or IL-6. With IL-4, 3H-TdR incorporation was increased in the cells from 2 out of 5 patients with CD7+4-8- acute leukemia and in the cells of 2 of those with CD1+ acute leukemia. IL-5 increased the 3H-TdR incorporation by cells from 2 out of 5 patients with CD7+4-8- acute leukemia and 1 patient with CD1+ acute leukemia. IL-7 increased 3H-TdR incorporation in cells from all five CD7+4-8- acute leukemia and 2 of those with CD5+ or CD1+ leukemia. No synergistic effect was found when IL-7 and other cytokines were added to cells from the 3 patients with CD7+4-8- acute leukemia who were tested.

We investigated the effects of recombinant human interleukins 1 to 6 (rIL-1 to -6) on the proliferation of blast cells from patients with acute lymphoblastic leukemia (ALL). The 3H-TdR incorporation in the presence of various cytokines was examined in cells from 14 patients: 12 with B-lineage ALL, 1 with T-lineage ALL and 1 with biphenotypic leukemia. In B-lineage ALL, a significant increase in 3H-TdR incorporation was observed in 5/12 cases (42%) in the presence of rIL-1 alpha, in 10/12 cases (83%) with rIL-2, in 9/12 cases (75%) with rIL-3, in 3/6 cases (50%) with rIL-4, in 4/6 cases (67%) with rIL-5, and in 4/12 cases (33%) with rIL-6. The mean stimulation index of the cells showing a positive response was 1.74 for rIL-1 alpha, 3.40 for rIL-2, 2.55 for rIL-3, 1.86 for IL-4, 1.56 for rIL-5, and 2.97 for rIL-6. T-lineage ALL cells were stimulated only in the presence of rIL-2, and biphenotypic leukemia cells were not stimulated by any of the cytokines tested.