2'-Chlorodeoxyadenosine: evaluation of a novel predominantly lymphocyte selective agent in lymphoid malignancies

Hickish, Tamas; Serafinowski, P.; Cunningham, David; Oza, Amit M.; Dorland, E.; Judson, Ian; Millar, B. Cherie; Lister, T. A.; Roldán, Alberto

doi:10.1038/bjc.1993.24

Cited by 50 publications

(8 citation statements)

References 12 publications

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“…Other studies reported response rates ranging from 43% to 75% in pretreated patients, but with higher proportions of CR (16,(18)(19)(20). This could be explained by the number of different chemotherapy regimens, always more than 2, that our B-NHL patients received before 2-CdA.…”

Section: -Cda In B-cell Chronic Disordersmentioning

confidence: 70%

2‐Chlorodeoxyadenosine in the treatment of relapsed/refractory chronic lymphoproliferative disorders

Rondelli

Lauria

Zinzani

et al. 1997

European J of Haematology

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2‐Chlorodeoxyadenosine (2‐CdA) is a purine analog with cytotoxic activity on both resting and cycling lymphocytes which has been used as salvage therapy in advanced/resistant chronic lymphoproliferative disorders. In our study 39 patients (19 B‐CLL, 5 B‐PLL, 9 low‐grade B‐NHL, 5 CTCL and 1 high‐grade T‐NHL) who relapsed or became resistant after 1–4 chemotherapy regimens were treated with 2‐CdA 6 mg/m2 per day by 2 h infusion for 5 d every 28 d. The overall clinical response rate, including complete remission (CR) and partial remission (PR), was 66%. Two of 19 (10%) B‐CLL patients achieved a CR lasting 9 months, while 11/19 B‐CLL (58%) and 4/5 B‐PLL (3 B‐PLL/B‐CLL and 1 B‐PLL) (80%) achieved a PR. Interestingly, 5 of 6 patients who had been previously treated with fludarabine obtained a clinical response (2 CR and 3 PR). One of 9 (11%) low‐grade B‐NHL patients achieved a CR and relapsed after 26 months, and 5/9 (55%) achieved a PR. One of 5 (20%) CTCL achieved a CR lasting 32 months, while 2/5 (40%) achieved a PR. The overall mean duration of PR was 7.4 months and no differences were observed among different groups of patients. Toxicity was acceptable, as only a transient severe hematological impairment was observed in 20% of the patients while nonhematological toxicity was not documented. Two patients died because of bacterial pneumonia, 1 of meningitis due to Listeria and 9 from progression of the disease. In conclusion, treatment with 2‐CdA in heavily pretreated patients with chronic lymphoproliferative disorders is well tolerated and obtains high response rates, even in patients relapsed after treatment with fludarabine.

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Section: -Cda In B-cell Chronic Disordersmentioning

confidence: 70%

2‐Chlorodeoxyadenosine in the treatment of relapsed/refractory chronic lymphoproliferative disorders

Rondelli

Lauria

Zinzani

et al. 1997

European J of Haematology

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“…Pancytopenia has not been a notable finding of others ad ministering this drug in multiple courses to a variety of pa tients with hematologic diseases [3][4][5][6][7], However, we re cently found that 1 of 7 solid tumor patients given two courses of cladribine, 0.1 mg/kg/day for 7 days, developed severe thrombocytopenia [8], This patient with far ad vanced malignant melanoma had been extensively pre treated with interleukin-2, interferon, and with lymphokinc-activatcd killer cells.…”

Section: Discussionmentioning

confidence: 99%

Marrow Suppression Produced by Repeated Doses of Cladribine

et al. 1994

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2-Chlorodeoxyadenosine (cladribine, Leustatin®) is being used extensively in the treatment of hematologic malignancies, but relatively little is known regarding its toxicity to the normal marrow. Long-term serial hematologic observations have been made on 29 patients with multiple sclerosis undergoing experimental therapy with monthly courses of cladribine, each of which consisted of 0.087-0.1 mg/kg per day for 7 days. The characteristic hematologic responses of the patients consisted of acute transient monocytopenia, prolonged, profound lymphopenia especially of CD4-positive cells, and modest lowering of the granulocyte count and hemoglobin with development of long-lasting macrocytosis. Two patients developed severe aplastic anemia, requiring transfusion both of red cells and platelets. One of these had previously received extensive therapy with chlorambucil, while the other had received carbamazepine (Tegretol®) and was ingesting phenytoin (Dilantin®) at the time of cladribine therapy. Both patients recovered after several months of marrow suppression.

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“…[26][27][28][29][30][31][32][33][34][35][36] Cladribine demonstrated impressive activity with overall and CR rates of up to 72% and 38%, respectively. Follicular and nonfollicular histologies appeared to be equally responsive.…”

Section: Single-agent Therapy In Previously Treated Indolent Nhlmentioning

confidence: 99%