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Antimetabolites
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The most common side effects of fludarabine treatment include diarrhea, anorexia, edema, pneumonia, cough, peripheral neuropathy, visual disturbances, chills, fever, malaise, weakness, and rash. Less common side effects include immune-mediated hemolytic anemia, thrombocytopenia and neutropenia, and myelosuppression may be cumulative. If immunosuppression occurs, co-trimoxazole is co-administered to prevent pneumocystis infection. Patients must also be monitored for signs of hemolysis, neurological toxicity, and worsening of existing (or increased susceptibility to) skin cancer. It follows that fludarabine is contra-indicated in hemolytic anemia. The dose must be reduced in patients with renal impairment, and due to its teratogenic effects, a six-month contraceptive policy for both males and females is recommended.
Haematological malignancy
Published in Peter Hoskin, Peter Ostler, Clinical Oncology, 2020
Oral alkylating agents are usually relatively trouble free, provided careful attention is paid to the blood count and treatment stopped when there are signs of significant bone marrow depression. Fludarabine may exacerbate haemolytic anaemia.
Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Ann E. Traynor, Richard K. Burt, Alberto Marmont
There certainly will be further refinements verging on conditioning regimens, more specifically lympholytic, such as the combination of cyclophosphamide and Rituximab to achieve B-cell depletion. Fludarabine may also be considered, but it would be ill advised to use fludarabine due to known CNS toxicity of fludarabine in patients with renal insufficiency. A phase III NIH funded trial is being developed to compare the efficacy of HSCT to a continuation of the currently accepted standard of care, intravenous monthly cyclophosphamide in persistent, active SLE. The same mobilization and conditioning regimen will be used in the phase III trial as in the phase I/II Northwestern trial discussed above. Stem cells will mobilized with cyclophosphamide (2.0 g/ m2) followed 48-72 hours later with daily G-CSF (10 mcg/kg/ day). The conditioning regimen will be cyclophosphamide (200 mg/kg) and equine ATG (90 mg/kg). In selecting candidates for this Phase III trial, it was imperative that rheumatologists feel that the standard approach appeared to be failing before they randomize their patient. Therefore, patients with nephritis as their eligibility criterion will need to have received 6 cycles of cyclophosphamide and still have active disease. For other organ systems, the standard of treatment is less well established.
Current therapies for chronic lymphocytic leukemia: risk and prophylaxis strategies for secondary/opportunistic infections
Published in Expert Review of Hematology, 2023
Lucia Diella, Davide Fiore Bavaro, Giacomo Loseto, Crescenza Pasciolla, Carla Minoia, Daniela Di Gennaro, Alessandra Belati, Maria Stella De Candia, Francesco Di Gennaro, Annalisa Saracino, Attilio Guarini
Risk of reactivation of latent tuberculosis infection (LTBI) is higher in patients affected by CLL if compared to general population, due to immunosuppression related either to disease or to chemotherapy [36]. Therefore, screening for LTBI should be preferably performed by Quantiferon TB Gold at time of CLL diagnosis, particularly in countries where incidence of tuberculosis is high [60]. Overall, antitubercular prophylaxis is advisable in patients with LTBI who will be exposed to immunosuppressive therapies or novel agents. Interestingly, among different drugs used for CLL therapy, the use of fludarabine is considered particularly at risk of developing active tuberculosis [61]. According to Sánchez-García et al., no specific safety and adherence issues are expected in CLL patients, since studies showed that incidence of adverse events related to anti-tuberculosis therapy is comparable among hematological patients and general population [62].
Recommendations for pregnancy in Fanconi anemia
Published in Expert Opinion on Biological Therapy, 2021
Charbel F. Matar, Rayan Bou-Fakhredin, Roberta Russo, Immacolata Andolfo, Achille Iolascon, Ali T. Taher
It is important to underline that because there is an increased sensitivity to DNA-damaging agents in FA, the use of an attenuated conditioning regimen before HSCT is necessary to avoid fatal toxicity [56]. However, FA patients who have undergone HSCT may still present with toxicity levels that are comparable to that of patients who have been transplanted for other diseases given conventional conditioning regimens. A major association between severity of toxicity after HSCT and severity of FA has been shown by Guardiola et al. [58]. Sterility was found to be among the most frequent toxicities observed after HSCT [53,54]. Therefore, the risk of permanent secondary amenorrhea and sterility appears to be higher in female patients grafted for FA. Therefore, all patients must be aware and presented with all potential risks before HSCT. Current regimens use fludarabine, which can decrease toxicity and improve engraftment. The use of fludarabine and low-dose cyclophosphamide has also shown favorable outcomes. In the case of HSCT from an HLA-unrelated donors, most centers are currently using fludarabine, low-dose cyclophosphamide and TBI 2 Gy [58–62].
Exploiting gene mutations and biomarkers to guide treatment recommendations in mantle cell lymphoma
Published in Expert Review of Hematology, 2021
While maintenance is currently a part of the standard of care, several questions are still unanswered. First, the benefit of maintenance depends on the type of induction chemoimmunotherapy used. After FCR, rituximab maintenance has been associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). The toxicity of rituximab maintenance has been found to be low after R-CHOP (grade 3–4 leukopenia or infection < 5%), however, it is more prominent in patients on rituximab maintenance after FCR, frequently carrying grade 3–4 leukopenia (up to 40%) and infections (up to 15%). The well-established immunotoxicity of fludarabine may be responsible for this increased toxicity. Similarly, bendamustine has been reported to be associated with lymphopenia [86], which may explain the discordant data obtained with B-R maintenance in various trials; for instance, in the MAINTAIN trial (B-R x 6 cycles followed by either maintenance rituximab (1 q 2 mos x 2 years) vs observation) involving 120 patients with newly diagnosed MCL, maintenance rituximab did not improve outcome [87]. This was also seen in a recent meta-analysis in which six trials involving 858 patients with MCL were included, suggesting a benefit for rituximab maintenance, while it remained unclear if maintenance was beneficial after induction chemotherapy with bendamustine or fludarabine [88]. Newer regimens of maintenance with R2 or BTKi may help overcome this issue and provide a rationale for studies that are still ongoing in both younger and elderly patients.