BACKGROUND

Anemia is common in cancer patients, although the prevalence is influenced both by the type of malignancy and the choice of treatment. Individual studies have compared the survival of patients with and without anemia and have shown reduced survival times in patients with various malignancies, including carcinoma of the lung, cervix, head and neck, prostate, lymphoma, and multiple myeloma. The objective of this study was to systematically review, to summarize, and to obtain an overall estimate of the effect of anemia on survival in patients with malignant disease.



METHODS

A comprehensive literature review was carried out using the MEDLINE data base and reviewing the reference lists from published studies. Two hundred papers were identified. Of these, 60 papers that reported the survival of cancer patients according to either hemoglobin levels or the presence of anemia were included. Among these papers, 25% related to patients with lung carcinoma, 17% related to patients with head and neck carcinoma, 12% related to patients with multiple myeloma, 10% related to patients with prostate carcinoma, 8% related to patients with cervicouterine carcinoma, 7% related to patients with leukemia, 5% related to patients with lymphoma, and 16% related to patients with other types of malignancies.



RESULTS

The relative risk of death increased by 19% (95% confidence interval, 10–29%) in anemic patients with lung carcinoma, by 75% (37–123%) in anemic patients with head and neck carcinoma, by 47% (21–78%) in anemic patients with prostate carcinoma, and by 67% (30–113%) in anemic patients with lymphoma. The overall estimate increase in risk was 65% (54–77%).



CONCLUSIONS

Anemia is associated with shorter survival times for patients with lung carcinoma, cervicouterine carcinoma, head and neck carcinoma, prostate carcinoma, lymphoma, and multiple myeloma. Cancer 2001;91:2214–21. © 2001 American Cancer Society.

Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review.

BACKGROUND: Treatment of cancer is increasingly more effective but is associated with short and long term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. One of these side effects is oral mucositis (mouth ulcers). OBJECTIVES: To evaluate the effectiveness of prophylactic agents for oral mucositis in patients with cancer receiving treatment, compared with other potentially active interventions, placebo or no treatment. SEARCH STRATEGY: Electronic searches of Cochrane Oral Health Group and PaPaS Trials Registers (to 16 February 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 16 February 2011), EMBASE via OVID (1980 to 16 February 2011), CINAHL via EBSCO (1980 to 16 February 2011), CANCERLIT via PubMed (1950 to 16 February 2011), OpenSIGLE (1980 to 2005) and LILACS via the Virtual Health Library (1980 to 16 February 2011) were undertaken. Reference lists from relevant articles were searched and the authors of eligible trials were contacted to identify trials and obtain additional information. SELECTION CRITERIA: Randomised controlled trials of interventions to prevent oral mucositis in patients receiving treatment for cancer. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions, outcome measures, results and risk of bias were independently extracted, in duplicate, by two review authors. Authors were contacted for further details where these were unclear. The Cochrane Collaboration statistical guidelines were followed and risk ratios calculated using random-effects models. MAIN RESULTS: A total of 131 studies with 10,514 randomised participants are now included. Overall only 8% of these studies were assessed as being at low risk of bias. Ten interventions, where there was more than one trial in the meta-analysis, showed some statistically significant evidence of a benefit (albeit sometimes weak) for either preventing or reducing the severity of mucositis, compared to either a placebo or no treatment. These ten interventions were: aloe vera, amifostine, cryotherapy, granulocyte-colony stimulating factor (G-CSF), intravenous glutamine, honey, keratinocyte growth factor, laser, polymixin/tobramycin/amphotericin (PTA) antibiotic pastille/paste and sucralfate. AUTHORS' CONCLUSIONS: Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment. The strength of the evidence was variable and implications for practice include consideration that benefits may be specific for certain cancer types and treatment. There is a need for further well designed, and conducted trials with sufficient numbers of participants to perform subgroup analyses by type of disease and chemotherapeutic agent.

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Interventions for treating oral mucositis for patients with cancer receiving treatment.

Background Adult Burkitt-type lymphoma (BL) and acute lymphoblastic leukemia (B-ALL) are rare entities composing 1% to 5% of non-Hodgkin lymphomas NHL) or ALL. Prognosis of BL and B-ALL has been poor with conventional NHL or ALL regimens, but has improved with dose-intensive regimens. Methods To evaluate the addition of rituximab, a CD20 monoclonal antibody, to intensive chemotherapy in adults with BL or B-ALL, 31 patients with newly diagnosed BL or B-ALL received the hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen with rituximab. Their median age was 46 years; 29% were 60 years or older. Rituximab 375 mg/m(2) was given on Days 1 and 11 of hyper-CVAD courses and on Days 1 and 8 of methotrexate and cytarabine courses. Results Complete remission (complete response [CR]) was achieved in 24 of 28 (86%) evaluable patients; 3 had a partial response, and 1 had resistant disease. There were no induction deaths. The 3-year overall survival (OS), event-free survival, and disease-free survival rates were 89%, 80%, and 88%, respectively. Nine elderly patients achieved CR with all of them in continuous CR (except 1 death in CR from infection), with a 3-year OS rate of 89%. Multivariate analysis of current and historical (those treated with hyper-CVAD alone) groups identified age and treatment with rituximab as favorable factors. Conclusions The addition of rituximab to hyper-CVAD may improve outcome in adult BL or B-ALL, particularly in elderly patients.

/pdf/chemoimmunotherapy-with-hyper-cvad-plus-rituximab-for-the-2yme9haeto.pdf

Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia

These studies were undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on ovarian function and reproductive outcomes. We reviewed the frequency of acute ovarian failure, premature menopause, live birth, stillbirth, spontaneous and therapeutic abortion and birth defects in the participants in the Childhood Cancer Survivor Study (CCSS). Acute ovarian failure (AOF) occurred in 6.3% of eligible survivors. Exposure of the ovaries to high-dose radiation (especially over 10 Gy), alkylating agents and procarbazine, at older ages, were significant risk factors for AOF. Premature nonsurgical menopause (PM) occurred in 8% of participants versus 0.8% of siblings (rate ratio = 13.21; 95% CI, 3.26 to 53.51; P < .001). Risk factors for PM included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score, and a diagnosis of Hodgkin's lymphoma. One thousand two hundred twenty-seven male survivors reported they sired 2,323 pregnancies, and 1,915 female survivors reported 4,029 pregnancies. Offspring of women who received uterine radiation doses of more than 5 Gy were more likely to be small for gestational age (birthweight < 10 percentile for gestational age; 18.2% v 7.8%; odds ratio = 4.0; 95% CI, 1.6 to 9.8; P = .003). There were no differences in the proportion of offspring with simple malformations, cytogenetic syndromes, or single-gene defects. These studies demonstrated that women treated with pelvic irradiation and/or increasing alkylating agent doses were at risk for acute ovarian failure, premature menopause, and small-for-gestational-age offspring. There was no evidence for an increased risk of congenital malformations. Survivors should be generally reassured although some women have to consider their potentially shortened fertile life span in making educational and career choices.

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Ovarian Failure and Reproductive Outcomes After Childhood Cancer Treatment: Results From the Childhood Cancer Survivor Study

Treatment with cytotoxic chemotherapy and radiotherapy is associated with significant gonadal damage in men, and alkylating agents are the most common agents implicated. The vast majority of men receiving procarbazine-containing regimens for the treatment of lymphomas are rendered permanently infertile, whereas treatment with doxorubicin hydrochloride (Adriamycin), bleomycin, vinblastine, and dacarbazine appears to have a significant advantage, with a return to normal fertility in the vast majority of patients. Cisplatin-based chemotherapy for testicular cancer results in temporary azoospermia in most men, with a recovery of spermatogenesis in about 50% of the patients after 2 years and 80% after 5 years. The germinal epithelium is very sensitive to radiation-induced damage, with changes to spermatogonia following as little as 0.2 Gy. Testicular doses of less than 0.2 Gy had no significant effect on FSH levels or sperm counts, whereas doses between 0.2 and 0.7 Gy caused a transient dose-dependent increase in FSH and reduction in sperm concentration, with a return to normal values within 12-24 months. No radiation dose threshold has been defined above which permanent azoospermia is inevitable; however, doses of 1.2 Gy and above are likely to be associated with a reduced risk of recovery of spermatogenesis; the time to recovery, if it is to occur, is also likely to be dose dependent.

/pdf/spermatogenesis-after-cancer-treatment-damage-and-recovery-1qduzhfzmv.pdf

Spermatogenesis After Cancer Treatment: Damage and Recovery

Gonadal functions were evaluated in 92 male patients after treatment for advanced Hodgkin's disease The patients received six to ten cycles of cyclophosphamide, vincristine, procarbazine, and prednisolone (COPP) chemotherapy All patients were in remission and were followed for 1 to 17 years (median, 6) Testicular atrophy was noticed in 89 (967%) patients All patients remained azoospermic during the period of follow-up The testosterone levels did not differ before and after treatment The follicle stimulating hormone levels rose from pretreatment values (mean +/- standard deviation) of 17927 +/- 2199 ng/ml to 57879 +/- 10236 ng/ml after the treatment; the rise was significant (P less than 0001) The luteinizing hormone levels rose from pretreatment values of 10696 +/- 2037 ng/ml to 12737 +/- 3219 ng/ml after treatment; the rise was significant (P less than 005) Testicular biopsy specimens in 19 patients showed germinal aplasia in all cases It is concluded that six or more cycles of COPP chemotherapy for advanced Hodgkin's disease in men leads to permanent sterility

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819900501%2965%3A9%3C1903%3A%3AAID-CNCR2820650905%3E3.0.CO%3B2-%23

Testicular dysfunction after cyclophosphamide-vincristine-procarbazine-prednisolone chemotherapy for advanced Hodgkin's disease. A long-term follow-up study.

Primary non-Hodgkin's lymphoma of bone.

5 patients developed acute nonlymphocytic leukemia (ANLL) 2–4 years following the use of various cytotoxic agents for other primary disease. Alkylating agents were responsible for development of ANLL in 3 patients while mitomycin-C and methotrexate appear to be linked with leukemia transformation in the remaining 2 patients. 3 patients had a prolonged preleukemic phase preceding ANLL. Pancytopenia observed in 4 of 5 patients favors drug-induced stem cell damage leading to relatively resistant leukemia. Although the incidence of secondary leukemia is not very high, careful use of cytotoxic agents is needed to minimize therapy-linked neoplasms.

Therapy-Related Leukemia

Pattern of subtypes of acute lymphoblastic leukemia in India

Acute Lymphatic Leukemia (ALL) patients seen during the period 1974-1978 at the Tata Memorial Hospital. Bombay, are analyzed retrospectively to evaluate the clinical features at presentation, results of sequential therapy, and prognostic factors. A total of 301 patients were registered during the study period. There were 153 evaluable patients. Of these 73 patients received induction therapy with vincristine and prednisolone (VP) followed by cranial prophylaxis (cranial radiotherapy, 2,400 rads, and 10 weekly intrathecal injections of methotrexate 7.5 mg/m20 and continuous oral maintenance with daily 6-mercaptopurine and weekly methotrexate (group A). Another 39 patients (group B) received pulse therapy with vincristine and prednisolone during maintenance therapy. Finally 41 patients (group C) received L-asparaginase during induction and pulse therapy in addition to drugs as in group A. Of the 153 patients, 88 (58%) achieved complete response after induction treatment. Induction remission was 53% with vincristine and prednisolone (group A and group B), whereas it was 70% in group C. The difference in complete response rate in group C was statistically significant (P less than 0.05). The 3-year survival in our series was 22%, with median survival of 11 months. Group C patients receiving L-asparaginase along with vincristine and prednisolone showed 41% 3-year survival compared to 16% for group B. The 3-year survival in group A patients was only 7%, probably owing to lack of pulse therapy during maintenance treatment. The prognostic factors such as age, sex, WBC count, and mediastinal node were compared for induction remission and total survival. Possible factors relating to poor results in our series as compared to developed countries are discussed.

Gopal R

Papers

Testicular dysfunction after cyclophosphamide-vincristine-procarbazine-prednisolone chemotherapy for advanced Hodgkin's disease. A long-term follow-up study.

Primary non-Hodgkin's lymphoma of bone.

Therapy-Related Leukemia

Pattern of subtypes of acute lymphoblastic leukemia in India

Acute lymphoblastic leukemia: end-result analysis of treatment and prognostic factors in Indian patients.