Several studies of high-dose chemotherapy with either autologous or allogeneic bone marrow support show rapid bone loss in the first few years after transplantation.143 In of itself, standard doses of adjuvant chemotherapy cause small amounts of bone loss independent of CIOF causing hypogonadism.118 Direct and indirect effects of high-dose chemotherapy, in addition to hypogonadism, include factors that increase bone resorption (eg, renal dysfunction with decreases in 1,25[OH]2 vitamin and secondary hyperparathyroidism, glucocorticoids) and decrease new bone formation (eg, malabsorption to as a result of graft-versus-host disease or mucositis with resultant decrease in vitamin D and calcium absorption, and the direct inhibitory effects of chemotherapy on osteoblasts).144 There are several randomized studies of oral or IV bisphosphates at osteoporosis treatment dosing showing BMD increases in patients who have received allogenic transplantation.111 There are no fracture prevention data in this population.
Patients with chronic (> 6 months) glucocorticoid use.
Treatment with glucocorticoids over a long-term period can lead to drug-induced osteoporosis, which has been associated with rapid and significant bone loss.145 As such, the resulting increased vertebral fracture risk occurs at higher BMD thresholds in glucocorticoid-induced osteoporosis.145 The American College of Rheumatology recently released a guideline on the assessment, prevention, and treatment of glucocorticoid-induced osteoporosis in patients taking prednisone at doses > 2.5 mg per day for 3 or more months.79 Based on a systematic review of the literature, recommendations are made for treating only with calcium and vitamin D in adults who are at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred, when appropriate) in adults at moderate-to-high fracture risk, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive glucocorticoid treatment. The ASCO Expert Panel did not further update the American College of Rheumatology’s systematic review and supports their recommendations for the management of patients on long-term glucocorticoids.

For patients who do not have any of the high-risk conditions or treatments, the Expert Panel recommends consideration of clinical risk prediction tools to guide bone density testing. The accuracy of these tools, including simple ones that use only a few risk factors, has been judged to be moderate for predicting osteoporosis for patients without cancer. Although no study has yet validated any of the tools in cancer populations, the panel believes that they offer a valuable way to quantify risk for counseling and decision making about additional testing.
We also note the importance of incorporating cancer treatments into initial and follow-up assessments of osteoporosis and fracture risk. A number of studies have reported particularly rapid bone losses with cancer treatments that induce hypogonadism or early menopause, or directly block estrogen or testosterone effects on bone.78 Although many of these studies have not been large enough to assess fractures directly, it is clear that cumulative bone losses after several years can be very large, as summarized in Table 3, and all patients receiving these treatments should receive baseline testing and close follow up. Glucocorticoid effects on bone are also large, but a number of studies suggest that the effects of short-term regimens used in most cancer treatments are small or rapidly reversible. Long-term use (eg, 3 or more months) of glucocorticoid doses equivalent to prednisone greater than 2.5 mg per day or higher confer high fracture risk, however, and evaluation and treatment of such patients should follow guidelines that are specifically focused on them.79

Infections are a common complication in CLL patients; therefore, use of immunosuppressive agents, as for example corticosteroids, should be restricted to a possible minimum. The use of prophylactic systemic immunoglobulin does not have an impact on OS [
Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. A randomized, controlled clinical trial. Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia.
], and is only recommended in patients with severe hypogammaglobulinaemia and repeated infections [I, A]. Antibiotic and antiviral prophylaxis should be used in patients with recurrent infections and/or very high risk of developing infections (e.g. pneumocystis prophylaxis with co-trimoxazole during treatment with chemoimmunotherapies based on purine analogues or bendamustine) [IV, B]. Pneumococcal vaccination as well as seasonal influenza vaccination is recommended in early-stage CLL [IV, B].
Response evaluation includes a careful physical examination and a blood cell count. A bone marrow biopsy may be carried out to define CR [III, B] [
Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines.
Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines.
]. Patients who are MRD-negative after therapy show a longer response duration and survival. Additional clinical consequences of MRD positivity post-therapy remain unclear except for patients after an allogeneic transplantation, where a positive MRD signal may trigger the reduction of immunosuppressive therapies or the start of anti-leukaemic maintenance therapy. Therefore, MRD assessment is not generally recommended for monitoring post-therapy outside clinical studies.