Jack Lindh

Art therapy improves coping resources: A randomized, controlled study among women with breast cancer

OBJECTIVE Women with breast cancer suffer from considerable stress related to the diagnosis, surgery, and medical treatment. It is important to develop strategies to strengthen coping resources among these women. Research in art therapy has shown outcomes such as an increase in self-esteem and cohesion, significant improvement in global health, and a decrease in anxiety and depression. The aim of the present article was to describe the effects of an art therapy intervention program on coping resources in women with primary breast cancer. METHOD In this article, we report some of the results from a study including 41 women, aged 37-69 years old, with nonmetastatic primary breast cancer, referred to the Department of Oncology at Umeå University Hospital in Sweden for postoperative radiotherapy. The women represented various socioeconomic backgrounds. They were randomized to a study group (n = 20) with individual art therapy for 1 h/week during postoperative radiotherapy or to a control group (n = 21). The article focuses on changes in coping resources, as measured by the Coping Resources Inventory (CRI) before and 2 and 6 months after the start of radiotherapy. The study protocol was approved by the Umeå University Ethical Committee at the Medical Faculty (archive number 99-386). RESULTS There was an overall increase in coping resources among women with breast cancer after taking part in the art therapy intervention. Significant differences were seen between the study and control groups in the social domain on the second and third occasions. Significant differences were also observed in the total score on the second occasion. SIGNIFICANCE OF RESULTS This study shows that individual art therapy provided by a trained art therapist in a clinical setting can give beneficial support to women with primary breast cancer undergoing radiotherapy, as it can improve their coping resources.

Art therapy improves experienced quality of life among women undergoing treatment for breast cancer: a randomized controlled study

Women with breast cancer are naturally exposed to strain related to diagnosis and treatment, and this influences their experienced quality of life (QoL). The present paper reports the effect, with regard to QoL aspects, of an art therapy intervention among 41 women undergoing radiotherapy treatment for breast cancer. The women were randomized to an intervention group with individual art therapy sessions for 1 h/week (n = 20), or to a control group (n = 21). The WHOQOL-BREF and EORTC Quality of Life Questionnaire-BR23, were used for QoL assessment, and administrated on three measurement occasions, before the start of radiotherapy and 2 and 6 months later. The results indicate an overall improvement in QoL aspects among women in the intervention group. A significant increase in total health, total QoL, physical health and psychological health was observed in the art therapy group. A significant positive difference within the art therapy group was also seen, concerning future perspectives, body image and systemic therapy side effects. The present study provides strong support for the use of art therapy to improve QoL for women undergoing radiotherapy treatment for breast cancer.

Clonal rearrangements in childhood and adult precursor B acute lymphoblastic leukemia: a comparative polymerase chain reaction study using multiple sets of primers

Abstract: Ig heavy chain (IgH) and T‐cell receptor (TCR) gene rearrangements were investigated by polymerase chain reaction (PCR) amplification of diagnostic tumour samples from 91 patients (57 children and 34 adults, with cut‐off at age 16) with precursor B acute lymphoblastic leukemia (ALL). Using primers directed to the framework regions (FR) 1, 2 and 3 of the IgH gene, clonal IgH rearrangements were observed in 82, 58 and 58%, respectively, whereas clonality was presented in 45 and 27% using primers hybridising to the TCR δ and γ genes. A combination of all five primer sets used resulted in 96% positive cases (children 100%, adults 88%). The frequency of clonal IgH rearrangements correlated to patient age with a significantly lower fraction of positive cases in the adult group. The concomitant usage of more than one VH family gene was similar for childhood and adult ALL, and an over‐representation of VH6 rearrangements was found in childhood ALL. Twenty‐five out of 91 cases (27%) displayed an oligoclonal pattern for either IgH or TCR gene rearrangements (children 37%, adults 12%). A comparative analysis of samples from different compartments was performed in 23 patients, and differences between two or three compartments were observed in seven cases. Unexpectedly large, clonally appearing PCR products of 540–715 bp were found in three leukemias and sequence analysis verified their clonal nature. In summary, using multiple sets of primers clonal rearrangements of IgH and TCR genes can be detected in a very high frequency, including previously neglected large size PCR products. A common heterogeneity was demonstrated in different compartments reflecting ongoing clonal evolution, which can make detection of minimal residual disease (MRD) in ALL troublesome. Therefore, we suggest that a minimum of three targets should be used to minimise false‐negative results.

Clonal evolution as judged by immunoglobulin heavy chain gene rearrangements in relapsing precursor-B acute lymphoblastic leukemia.

Abstract:  Oligoclonality and ongoing clonal evolution are common features in patients with precursor‐B (pre‐B) acute lymphoblastic leukemia (ALL), as judged by immunoglobulin heavy chain (IgH) gene rearrangement analysis. These features are considered to be results of secondary rearrangements after malignant transformation or emergence of new tumor clones. In the present study we analyzed the IgH gene rearrangement status in 18 cases with relapsing pre‐B ALL using variable heavy chain (VH) gene family specific polymerase chain reaction (PCR) amplification and single stranded conformation polymorphism (SSCP) analysis. Clonal IgH rearrangements were displayed in all leukemias but one, and altered rearrangement patterns occurred in five cases (29%), which were selected for detailed nucleotide sequence analysis. In one case, multiple subclones at diagnosis were suggested to be derived from a progenitor clone through joining of different VH germline gene segments to a pre‐existing D–JH complex (VH to D–JH joining). Evidence for VH gene replacement with identical N‐sequences at the VH‐D junction and a common D–JH region was observed in one case. Diversification at the VH–D junction consisting of heterogeneous N‐sequences were observed in one case. This molecular modification of the VH‐D region could fit a hypothesized “open‐and‐shut” mechanism. Nevertheless, despite these ongoing events at least one IgH rearrangement remained unchanged throughout the disease in most patients, indicating that the immunoglobulin heavy chain locus can be a suitable marker for detection of minimal residual disease (MRD).

Detailed clonality analysis of relapsing precursor B acute lymphoblastic leukemia : implications for minimal residual disease detection.

Genetic instability has important implications for detection of minimal residual disease (MRD) when the target is a clonal genetic marker revealed at diagnosis. A successful MRD detection approach requires a stable marker and for lymphoid leukemias clonal rearrangements of immunoglobulin (Ig) and T cell receptor (TCR) genes are commonly used. In the present study, Ig heavy chain (IgH) and TCR (gamma and delta) genes were studied in 18 consecutive, relapsing precursor-B ALL patients. At least one clonal rearrangement was found in all cases at presentation (IgH 94%, TCRgamma 39% and TCRdelta 28%). An altered rearrangement pattern between diagnosis and relapse was demonstrated in 14 patients (78%). At least one stable molecular target was found in 13 out of 18 cases (72%). Clonal differences between diagnostic and relapse samples were explained by: (1) loss of original rearrangements; (2) V(H) to DJ(H) joining; (3) V(H) gene replacement; (4) appearance of new rearrangements. In two cases with apparently new IgH gene rearrangements at relapse extended sequencing of the diagnostic samples revealed minor clonal rearrangements identical to the relapse clones. Interestingly, one patient displayed instability on both the IgH and TCR gene loci, whereas a stable Igkappa rearrangement was found at presentation and relapse. These data show that clonal diversity is common in precursor-B ALL and strongly suggest that MRD detection should include multiple gene targets to minimize false-negative samples. Even so, five of our 18 relapse cases (28%) lacked stable clonal markers and should have been unsuitable for MRD detection.

VH gene family utilization in different B-cell lymphoma subgroups

Abstract:  VH gene family specific polymerase chain reaction (PCR) amplification was performed in 87 B‐cell lymphoma samples from 4 different subgroups. No apparent restriction in the VH gene usage was found in follicular lymphomas, lymphoplasmacytoid lymphomas or large B‐cell lymphomas, whereas a biased Vh1 utilization was shown in patients with chronic lymphocytic leukemia. Eleven of 18 chronic lymphocytic leukemia cases utilized the VH1 gene family, and nucleotide sequencing of the VH1 gene rearrangements revealed that a majority utilized the DP10 (51p1) germline gene, which has been reported to be strongly associated with autoimmune disease. No VH5 or VH6 rearrangements were amplified in the chronic lymphocytic leukemia subgroup, 2 gene families which previously have been found to be over‐represented in these patients. In a high proportion (40%) of large B‐cell lymphomas, VH gene family‐specific PCR failed to amplify any rearrangement. Using primers hybridizing to the framework regions 2 and 3 and Southern blot analysis of the immunoglobulin heavy chain locus, clonal rearrangements were displayed in two‐thirds of these PCR negative cases. However, the rearrangement status could not be elucidated in 5 of 35 patients with large B‐cell lymphoma.

Individual brief art therapy can be helpful for women with breast cancer : A randomized controlled clinical study

OBJECTIVE Recent research shows that almost every second woman with breast cancer is depressed or has anxiety; the risk for younger women is even higher. Moreover, research shows that women are at risk for developing depression, also a threat for women with breast cancer. The aim of this randomized controlled clinical trial was to study the outcome of five sessions of art therapy given at a 5-week period of postoperative radiotherapy. METHODS The participants were between 37 and 69 years old; six participants in each group were below 50 years of age. Half of the participants (n = 20) received art therapy and the other half (n = 21) were assigned to a control group. At the first measurement, at least 17% (n = 7) of the participants medicated with antidepressants. Data were collected before and after art therapy and at a 4-month follow-up using self-rating scales that measure self-image (the Structural Analysis of Social Behaviour) and psychiatric symptoms (the Symptom Check List-90). RESULTS At follow-up, significant lower ratings of depression, anxiety, and somatic symptoms and less general symptoms were reported for the art therapy group compared to the control group. The regression analysis showed that art therapy relates to lower ratings of depression, anxiety, and general symptoms; chemotherapeutic treatment predicts lower depressive symptoms; in contrast to axillary surgery and hormonal treatment as well as being a parent predicts higher ratings of anxiety and general symptoms. SIGNIFICANCE OF RESULTS The conclusion suggests that art therapy has a long-term effect on the crisis following the breast cancer and its consequences.

NON-HODGKIN LYMPHOMA Multivariate analysis of prognostic factors including fraction of S-phase cells

In a material of 80 patients with non-Hodgkin lymphoma a multivariate analysis was carried out taking the following variables into account: Age, clinical stage, B-symptoms, morphologic diagnosis and fraction of S-phase cells in the tumour determined by flow cytometry. Clinical stage, proportion of cells in the S-phase, and age of the patient were significant independent prognostic factors. Morphologic malignancy grade and B-symptoms were not significant parameters in this analysis. It was concluded that DNA analysis with determination of the fraction of S-phase cells is a valuable complement to morphology in the evaluation of patients with non-Hodgkin lymphoma. In combination with the clinical stage it gives very good discrimination into groups with different prognoses.

Telomere length and telomerase activity in malignant lymphomas at diagnosis and relapse

Telomere length maintenance, in the vast majority of cases executed by telomerase, is a prerequisite for long-term proliferation. Most malignant tumours, including lymphomas, are telomerase-positive and this activity is a potential target for future therapeutic interventions since inhibition of telomerase has been shown to result in telomere shortening and cell death in vitro. One prerequisite for the suitability of anti-telomerase drugs in treating cancer is that tumours exhibit shortened telomeres compared to telomerase-positive stem cells. A scenario is envisioned where the tumour burden is reduced using conventional therapy whereafter remaining tumour cells are treated with telomerase inhibitors. In evaluating the realism of such an approach it is essential to know the effects on telomere status by traditional therapeutic regimens. We have studied the telomere lengths in 47 diagnostic lymphomas and a significant telomere shortening was observed compared to benign lymphoid tissues. In addition, telomere length and telomerase activity were studied in consecutive samples from patients with relapsing non-Hodgkins lymphomas. Shortened, unchanged and elongated telomere lengths were observed in the relapse samples. The telomere length alterations found in the relapsing lymphomas appeared to be independent of telomerase and rather represented clonal selection random at the telomere length level. These data indicate that anti-telomerase therapy would be suitable in only a fraction of malignant lymphomas.

Simultaneous immunoglobulin/T‐cell receptor gene rearrangements and multiclonality in childhood acute lymphoblastic leukemia

Twenty‐five children less than 16 years of age with acute lymphoblastic leukemia (ALL) were investigated with immunologic, cytogenetic and molecular genetic techniques at diagnosis. All pre‐B‐cell ALL showed clonal rearrangements in the immunoglobulin heavy chain gene (JH and/or Cμ). A very high proportion of the pre‐B‐cell leukemias (17 of 23 cases) also snowed clonal rearrangements in T‐cell receptor genes (Tγ and/or Tβ). The two T‐cell leukemias exhibited clonal T‐cell receptor gene rearrangements and in one Jh and kappa light chain rearrangments also. The T‐cell receptor gene rearrangements found in pre‐B‐cell leukemias appeared to occur randomly with respect to the Tβ and Tγ genes. A significant proportion of the leukemias (at least 24%) seemed to harbor more than one malignant (sub)clone at diagnosis. Cytogenetic studies revealed a clonal abnormality in 10 cases. Only 2 showed hyperdiploidy (> 50 chromosomes). The only correlation between cytogenetic findings and rearrangement patterns was extra bands corresponding to a possible trisomy of chromosome 14. Our data indicate, in line with previous studies, that childhood ALL has complex rearrangement patterns not useful for lineage sub‐classification. For this purpose immunophenotyping appears to be superior. However, molecular analysis can reveal the presence of more than one clone not detected by immunophenotyping or karyotyping, and distribution of clones in different compartments. In this study no correlation with clinical outcome was observed.