Is there a favorable subset of patients with prostate cancer who develop oligometastases?

OBJECTIVE: To analyze, retrospectively, the patterns and behavior of metastatic lesions in prostate cancer patients treated with external beam radiotherapy and to investigate whether patients with < or =5 lesions had an improved outcome relative to patients with >5 lesions. METHODS AND MATERIALS: The treatment and outcome of 369 eligible patients with Stage T1-T3aN0-NXM0 prostate cancer were analyzed during a minimal 10-year follow-up period. All patients were treated with curative intent to a mean dose of 65 Gy. The full history of any metastatic disease was documented for each subject, including the initial site of involvement, any progression over time, and patient survival. RESULTS: The overall survival rate for the 369 patients was 75% at 5 years and 45% at 10 years. The overall survival rate of patients who never developed metastases was 90% and 81% at 5 and 10 years, respectively. However, among the 74 patients (20%) who developed metastases, the survival rate at both 5 and 10 years was significantly reduced (p <0.0001). The overall survival rate for patients who developed bone metastases was 58% and 27% at 5 and 10 years, respectively, and patients with bone metastases to the pelvis fared worse compared with those with vertebral metastases. With regard to the metastatic number, patients with < or =5 metastatic lesions had superior survival rates relative to those with >5 lesions (73% and 36% at 5 and 10 years vs. 45% and 18% at 5 and 10 years, respectively; p = 0.02). In addition, both the metastasis-free survival rate and the interval measured from the date of the initial diagnosis of prostate cancer to the development of bone metastasis were statistically superior for patients with < or =5 lesions compared with patients with >5 lesions (p = 0.01 and 0.02, respectively). However, the survival rate and the interval from the date of diagnosis of bone metastasis to the time of death for patients in both groups were not significantly different, statistically (p = 0.17 and 0.27, respectively). CONCLUSIONS: Patients with < or =5 metastatic sites had significantly better survival rates than patients with >5 lesions. Because existing sites of metastatic disease may be the primary sites of origin for additional metastases, our findings suggest that early detection and aggressive treatment of patients with a small number of metastatic lesions is worth testing as an approach to improving long-term survival.     

Is there a role for complementary therapy in the management of leukemia?

Patients with leukemia often seek additional treatments not prescribed by their oncologist in an effort to improve their cancer treatment outcome or to manage symptoms. Complementary therapies are used in conjunction with traditional cancer treatments to decrease symptoms and side effects associated with cancer or cancer treatment, and to improve patients’ overall quality of life. Complementary therapies are distinct from so-called ‘alternative’ therapies, which are unproven, ineffective and may postpone or interfere with mainstream cancer treatment. Complementary therapies are pleasant, inexpensive, nonpharmacologic and effective. For patients with leukemia, the complementary therapies that are always appropriate include mind–body interventions, such as self-hypnosis, meditation, guided imagery and breath awareness. Massage and reflexology (foot massage) decrease symptoms with effects lasting at least 2 days following treatment. Acupuncture is very beneficial for symptom management without adverse consequences. Physical fitness with regular exercise and healthy dietary habits can significantly decrease side effects of cancer treatments and may prolong survival. Botanical extracts and vitamin supplements may interfere with active cancer treatments, and should be discussed with the oncologist or pharmacist before use.     

Extramedullary (EMP) relapse in unusual locations in multiple myeloma: Is there an association with precedent thalidomide administration and a correlation of special biological features with treatment and outcome?

Extramedullary relapse constitutes an uncommon manifestation of multiple myeloma (MM), characterized by highly malignant histology, special biological features, resistance to treatment and poor outcome. Its incidence has been increased during the last years, probably due to the introduction of novel strategies in the management of MM, including intensified treatment and immunomodulatory drugs. Here we report nine cases of extramedullary relapse of MM, presented in unusual locations, seven of which had previously been treated with thalidomide-containing regimens (TCR). Our aim was to explore the morphological, immunophenotypical, molecular and laboratory characteristics accompanying EMP-relapse and seek possible correlations with treatment and clinical outcome.     

Mean cell volume can be an early predictor for the cytogenetic response of chronic myeloid leukemia patients treated with imatinib?

Imatinib-induced macrocytic anemia was known to result from c-kit inhibition in chronic myeloid leukemia (CML). However, recent studies showed that the prevalence of anemia is increased with high trough imatinib level and increased doses of imatinib influence decreased proliferation of burst forming units-erythroids (BFU-Es). The aim of this study was to evaluate the continuously increased mean cell volume (MCV) level's correlation with cytogenetic response and the favorable outcome in early chronic phase (CP)–CML patients.Clinical importance of MCV level was evaluated to correlate with cytogenetic response and compared with Sokal score, a known excellent prognostic parameter of cytogenetic response (CCR) in 84 early CP–CML patients.The patients with early and continuously increased MCV level irrespective of anemia achieved higher CCR after 12 months of imatinib therapy than patients with non-CCR (p = 0.011). When the value was compared with low Sokal score, elevated MCV was independent predictor of CCR (RR = 12.925, p = 0.002 vs. RR = 35.445, p < 0.001). Furthermore, the patients with early and continuously increased MCV level had a higher probability of maintaining CCR than non-increased level (p = 0.019). Increased MCV level was surrogate marker of achievement and durability to CCR for early CP–CML patients in the present study.     

B-cell chronic lymphocytic leukemia risk in association with serum leptin and adiponectin: a case–control study in Greece

Aim  

Leptin and adiponectin are two well-studied adipokines in relation to malignancies. In this study, we examined the association between leptin/adiponectin and risk of B-cell chronic lymphocytic leukemia (B-CLL), as well as the relationships between adipokines and several established prognostic factors of B-CLL.     

Management and outcome of children with neuroendocrine tumors of the appendix in Spain: Is there room for improvement?

Purpose

Neuroendocrine tumors (NETs) are, after lymphomas, the most frequent gastrointestinal tumors in children, mainly located in the appendix. Best management remains unclear, given the absence of pediatric guidelines. We present the first Spanish series of pediatric patients with NETs.

Patients and methods

Retrospective study of all pediatric patients (<18 years) with NET treated in four oncology reference institutions in Spain between 1994 and 2015.

Results

Seventeen patients were included. All patients presented with acute abdomen. TNM stage was T1a (82%) and T1b (12%). Extension study was heterogenous, with only 4 patients undergoing an OctreoScan. Four patients met criteria for second surgery (affected surgical margins or mesoappendix invasion), but it was only performed in two. Despite the diverse management, none of the patients relapsed during follow-up.

Conclusions

The disparity in diagnostic tests, second surgery criteria and follow-up shown in this study highlights the need for specific pediatric guidelines.

     

Avascular necrosis of the femoral head in chronic myeloid leukemia patients treated with interferon-alpha: a synergistic correlation?

BACKGROUND: The objectives of this study were to describe cases of avascular necrosis of the femoral head (ANFH) observed in chronic myeloid leukemia (CML) patients who were treated with interferon-alpha and to review the literature. METHODS: The authors undertook a case review of the M. D. Anderson experience with ANFH occurring in CML patients who were managed with interferon-alpha-based therapy. MEDLINE (from 1966 to November 1999) and CancerLit (from 1983 to November 1999) searches were conducted to identify cases of avascular necrosis (AVN) associated with either CML or interferon-alpha. RESULTS: Three patients with ANFH were identified from the authors' experience. No common features related to the disease or therapy were seen among them, except for the presence of thrombocytosis and loss of response. A literature review revealed seven cases of ANFH associated with CML with or without interferon-alpha-based therapy. ANFH was not reported in association with interferon-alpha use for indications other than the treatment of patients with CML. CONCLUSIONS: ANFH may be the result of an interaction between CML and interferon-alpha therapy. ANFH that occurs in patients with CML who are treated with interferon-alpha should be recognized for treatment implications. Thrombocytosis with consequent microvascular thrombi and avascular necrosis manifesting in susceptible vascular or weight-bearing areas (e.g., the femoral head) may be an associated finding along with loss of response to interferon-alpha therapy.     

Is there a direct differentiation-inducing effect of human recombinant interferon on hairy cell leukemia in vitro?

We used a panel of monoclonal antibodies (moAb) to label splenic hairy cells from eight patients to determine the membrane phenotypes, the presence of cytoplasmic immunoglobulin (cIg), and the expression of maturation-associated antigens. All eight patients had responded clinically to splenectomy either alone or in combination with alpha-2b-interferon (alpha-IFN) therapy. For each sample, cytofluorimetric analysis showed distinct, and in six cases multiple, heavy chain isotypes. After short-term culture in the presence of alpha-IFN or gamma-interferon (gamma-IFN), samples from four patients displayed characteristic changes in surface immunoglobulin (sIg) expression. When compared with untreated cells, cells co-cultured with alpha-IFN or gamma-IFN showed in four and three patients, respectively, changes that were consistent with a shift to the more mature stage in B-cell ontogeny. However, in parallel with the changes in the sIg isotypes, treatment with IFN did not induce the appearance of cIg nor did the staining patterns for moAb to CD5, CD19, CD20, and CD22 antigens indicate the induction of terminal maturation. These data suggest that hairy cell leukemia (HCL), a neoplasm of "mature" B-cells, is potentially susceptible to maturation stimuli. Based on these findings, it might be of interest to examine whether co-factors, which have proved to play a role in HCL (e.g., B-cell growth factor [BCGF]), are capable of further enhancing IFN-induced differentiation.     

Dynamics of telomere erosion and its association with genome instability in myelodysplastic syndromes (MDS) and acute myelogenous leukemia arising from MDS: a marker of disease prognosis?

Telomere length was evaluated by terminal repeat fragment method (TRF) in 50 patients with myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML) arising from MDS and in 21 patients with untreated primary AML to ascertain, whether telomere erosion was associated with progression of MDS towards overt leukemia. Heterogeneity of TRF among MDS FAB subgroups (P=0.004) originated from its shortening in increased number of patients during progression of the disease. Chromosomal aberrations were present in 32% MDS patients with more eroded telomeres (P=0.022), nevertheless a difference between mean TRF in the subgroups with normal and abnormal karyotype diminished during progression of MDS. A negative correlation between individual TRF and IPSS value (P=0.039) showed that telomere dynamics might serve as a useful prognostic factor for assessment of an individual MDS patient's risk and for decision of an optimal treatment strategy.     

Allogeneic Peripheral Blood Stem Cell Transplantation: Is there an increased risk of graft vs host disease in leukemia patients?

Abstract

Fifteen patients with hematological malignancies [9 acute nonlymphoblastic leukemia (ANLL), four chronic myelogenous leukemia (CML), two acute lymphoblastic leukemia (ALL)] received allogeneic peripheral blood stem cell transplantation (alloPBSCT) from HLAidentical sibling donors. Donors received 2.5-15 μg/kg/day of recombinant human granulocyte colony stimulating factor (rhG-CSF) for 5-10 days. Administration of rhG-CSF was well tolerated except for mild to moderate bone pain occurring in all the donors which was relieved by oral paracetamol. A total of 40 leukaphereses were performed for the 15 donors using the bilateral antecubital veins. None of the donors needed central venous line insertion. The median number of apheresis procedures for each patient was 3 (2-3). A median of 7.7 (4-38.2) × 10⁸/kg mononuclear cells, 35 (2.4-90.0)x 10⁶/kg CD34+ cells, 1.85 (0.45-4.8) × 10⁸/kg CD3 and 0.3 (0.16-1.01) × 10⁸/kg natural killer cells were given without any manipulation. Cyclosporin A (CsA) plus short-course methotrexate (MTX) (12 patients) and CsA alone (3 patients) were used for graft versus host disease (GVHD) prophylaxis. Median granulocyte and platelet engraftments were done on days 11 (10-31) and 16 (11-54) respectively. Grades II-IV GVHD occurred in 62% of the patients and grades III-IV in 15%. Twelve patients are still alive with full engraftment and disease-free. In conclusion, alloPBSCT is an alternative to allogeneic bone marrow transplantation, because of the ease of collection and rapid hematological recovery. However, there is a trend for increased acute GVHD in our leukemia patients compared to allogeneic bone marrow.