Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up.

Hoffman, Mark A.; Janson, Dale; Rose, Esther; Rai, K R

doi:10.1200/jco.1997.15.3.1138

Cited by 113 publications

(68 citation statements)

References 16 publications

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“…These results confirm prior observations seen in older HCL patient populations that single courses of cladribine induce very high response rates, the majority of which are complete and durable, but with a risk of late relapse. 10,11,14,15 Salvage rates with second courses of cladribine in young HCL patients remain high, as has been documented in older HCL patients. A small, but increased incidence of second primary malignancies was observed in this young patient population; however, this was not statistically significant.…”

Section: Discussionmentioning

confidence: 82%

Clinical characteristics and long-term outcome of young hairy cell leukemia patients treated with cladribine: a single-institution series

Rosenberg

Burian

Waalen

et al. 2014

Blood

102

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Key Points• HCL patients #40 years at diagnosis treated with cladribine obtain complete and durable responses, but ultimately relapse.• There was no increased risk of second primary malignancies in young hairy cell leukemia patients followed for protracted periods.Hairy cell leukemia (HCL) is a rare, indolent B-cell disorder in which single courses of cladribine induce high rates of complete responses. We report on 88 young HCL patients (£40 years of age at diagnosis) treated with cladribine from the Scripps Clinic HCL Database, of whom 83 were evaluable for response. Seventy-three patients (88%) achieved an initial complete response and 10 (12%) a partial response, with a median response duration of 57 months. Forty-eight patients (58%) relapsed, with a median time to first relapse for all responders of 54 months. Eight patients developed 11 second primary malignancies with an excess frequency of 1.60 (95% confidence interval, 0.80-2.89). Thirteen (15%) patients died with a mortality ratio compared with age-matched normals of 1.85 (95% confidence interval, 1.07-3.18). Median overall survival for all patients following the first cladribine course was 231 months, and 251 months from diagnosis. Single courses of cladribine induce high rates of complete and durable responses in the majority of young HCL patients and are therefore recommended for HCL patients regardless of age. (Blood. 2014;123(2):177-183)

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Section: Discussionmentioning

confidence: 82%

Clinical characteristics and long-term outcome of young hairy cell leukemia patients treated with cladribine: a single-institution series

Rosenberg

Burian

Waalen

et al. 2014

Blood

102

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“…The relapse rate, DFS and survival associated with 2-CdA in pts with HCL are not well established, because only a few studies are concerned with a longer follow-up. [5][6][7][8][9] This purine analog has dramatically improved the clinical course and prognosis of this disorder, although responsible for neutropenia and lymphocytopenia often associated with fever of unknown origin or proven infectious complications. In our analysis, we wished to address several questions with regard to a long-term follow-up evaluation: what is the long-term prognosis for pts achieving remission with 2-CdA and what is the incidence of relapse?…”

Section: Discussionmentioning

confidence: 99%

“…Following these encouraging results, several studies have reported a long-term follow-up of 3-5 years after treatment with 2-CdA. [5][6][7][8][9] In this paper, we analyze the initial and long-term results at 10 years, such as clinical outcome, duration of response, toxicity and survival of 44 HCL pts uniformly treated with a single 7-day course of 2-CdA by continuous infusion. The experience of both pretreated pts, including splenectomy, interferon a (IFN) and deoxycoformycin (dCF), as well as previously untreated pts will be described.…”

Section: Introductionmentioning

confidence: 99%

An update: 12-year follow-up of patients with hairy cell leukemia following treatment with 2-chlorodeoxyadenosine

et al. 2004

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Long-term results of both pretreated and previously untreated patients (pts) with hairy cell leukemia (HCL) using uniformly a single 7-day course of 2-chlorodeoxyadenosine (2-CdA) by continuous infusion are reported. In addition, the probability of obtaining another response with this drug in pts who relapsed after 2-CdA treatment will be addressed. A total of 44 consecutive pts (34 males, 10 females) with a median age of 57 years (range 33-77) at the time of initiation of 2-CdA treatment were analyzed. In all, 11 pts were pretreated with either splenectomy (n ¼ 6), interferon a (n ¼ 9) or deoxycoformycin (dCF) (n ¼ 3) or all procedures in sequence. Two pts treated with dCF did not respond to dCF, but only 2-CdA. The median time to the start of 2-CdA treatment of the 11 pretreated pts was 47 months (mo) (10-160). Out of 44, 43 (98%) achieved complete response (CR) (13 pts with residual disease-RD), one pt reached a good partial response with a single cycle of 2-CdA. Out of 44 pts, 13 had no nonhematologic toxicities at all. Toxicities (WHO grade I-IV) were mainly of grade I and II, in one pt grade IV infectious complication. Bone marrow biopsies were performed at the time of recovery of hematopoiesis, thereafter at 2-3 mo intervals, thereafter at 6 mo, and finally annually in 35 pts. The median follow-up is 8.5 years (0.1-12.2). Disease-free survival from the start of 2-CdA treatment is 36% at 12 years (median 8.4 years), 17/44 pts relapsed. Nine of these pts were treated with 2-CdA again, eight achieved a second CR (median 2.5 yrs), one pt did not respond. Eight of our cohort had a second malignancy before receiving 2-CdA. Six pts died in CR due to the second malignancy. The overall survival at 12 years after the start of 2-CdA treatment is 79%. 2-CdA is a safe and effective treatment of HCL inducing complete remissions in the majority of pts with only a single cycle of 2-CdA, and a paucity of toxicities. Responses are durable and long-lasting. Pts who relapsed following treatment with 2-CdA responded to subsequent retreatment with 2-CdA.

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“…Our results presented here infer a possible additional mechanism of action for cladribine, which is prescribed for the treatment of hairy cell leukemia (HCL) [28]. HCL is an indolent leukemia, and thus although cladribine is a deoxyadenosine analogue and is directed toward DNA, the RNA-directed inhibition of polyadenylation may explain, in part, the actions towards RNA.…”

Section: Discussionmentioning

confidence: 98%

Polyadenylation inhibition by the triphosphates of deoxyadenosine analogues

2008

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The nucleotide substrate specificity of yeast poly(A) polymerase (yPAP) was examined with various ATP analogues of clinical relevance. The triphosphate derivatives of cladribine (2-CldATP), clofarabine (Cl-F-ara-ATP), fludarabine (F-ara-ATP), and related derivatives were incubated with yPAP and 32 P-radiolabeled RNA oligonucleotide primers in the absence of ATP to assay polyadenylation. While 2-Cl-ATP resulted in primer elongation, ara-ATP and F-ara-ATP were poor substrates for yPAP. In contrast, the triphosphate derivatives of cladribine (2-Cl-dATP), clofarabine (Cl-F-ara-ATP) and its corresponding deoxyribose derivative (Cl-F-dATP) were substrates and caused chain termination in the absence of ATP. We further investigated whether analog incorporation at the 3′-terminus of RNA primers negatively impacts polyadenylation with ATP by generating RNA oligonucleotides containing either a terminal clofarabine, Cl-F-dAdo, or cladribine residue. Incorporation of any of these analogs blocks the ability of yPAP to extend RNA past the analog site, impeding the addition of a poly(A)-tail. To determine whether modified ATP analogues exhibit a concentration dependent effect on polyadenylation, poly(A)-tail synthesis by yPAP with modified ATP analogues in combination with a constant level of ATP was also examined. With all the ATP analogues assayed in these studies, there was a significant reduction in poly(A)-tail length with increasing amounts of analog triphosphate. Taken together, our results suggest that polyadenylation inhibition may be a component in the mechanism of action of adenosine analogues.

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Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up.

Cited by 113 publications

References 16 publications

Clinical characteristics and long-term outcome of young hairy cell leukemia patients treated with cladribine: a single-institution series

Clinical characteristics and long-term outcome of young hairy cell leukemia patients treated with cladribine: a single-institution series

An update: 12-year follow-up of patients with hairy cell leukemia following treatment with 2-chlorodeoxyadenosine

Polyadenylation inhibition by the triphosphates of deoxyadenosine analogues

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