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Biomedical subjects

M Keating

Publications and source records attributed to M Keating.

At least 109 records · Page 6Linked to original sources
PubMed1996

Engraftment of chronic prolymphocytic and T cell leukemia in SCID mice.

Engraftment of human acute leukemia cells in immunocompromised (SCID) mice has resulted in in vivo models for exploration of human tumor biology. Attempts at engraftment of chronic leukemia cells have been generally unsuccessful. We have engrafted cells from three human chronic leukemias in SCID mice. Cell populations were from two patients with chronic lymphocytic leukemia (CLL) and either increased proolymphocytes (CLL-Pro; patient 1), or prolymphocytic transformation (PLL; patient 2) and from a third patient with newly diagnosed T cell CLL. Both fresh and cryopreserved cells were used and were injected intravenously, intraperitoneally, or both, after conditioning with cyclophosphamide. In addition, cells derived from a mouse spleen engrafted with human leukemia were passaged into another mouse. The animals were observed daily for signs of disease or appearance of tumors and sacrificed when terminally ill. At intervals blood samples were obtained and analyzed for the presence of human cells or DNA. Human leukemic cells were demonstrated by polymerase chain reaction (PCR) analysis of the human DQalpha gene or positive staining for human leukocyte common antigen (LCA). The presence of Epstein-Barr virus (EBV)-positive cells was also investigated by PCR analysis. Disseminated tumors developed in most mice inoculated with cells from the first patient, and this was associated with shortened survival times. The methods of administration, use of fresh or frozen samples, or the size of the inoculum had no effect on the development of leukemia. Survival of the mouse receiving passaged cells was similar to mice inoculated with fresh cells. Extensive histologic, immunophenotypic, and DNA studies were performed on organs from mice engrafting with cells from patient 1. PCR analysis for EBV sequences was negative in the mice engrafting from all three cases. The successful engraftment of human CLL-Pro PLL and T cell CLL in SCID mice, and the reproducibility of this effect using frozen cells, will provide a model for exploration of disease biology and for investigations of new drugs or combinations that may be useful in the treatment of CLL.

Aged↗
PubMed1995

Myeloid markers in adult acute lymphocytic leukemia. Correlations with patient and disease characteristics and with prognosis.

BACKGROUND: The expression of myeloid markers on lymphoblasts has been associated with adverse outcome in acute lymphocytic leukemia (ALL). The purpose of the study was to analyze the experience with adults treated at the University of Texas M. D. Anderson Cancer Center with myeloid marker- (MY) positive ALL in relation to patient and disease characteristics, response to therapy, and prognosis. METHODS: Since 1988, 64 of 162 adults (40%) with newly diagnosed ALL referred to our service had MY-positive ALL. Their characteristics and outcomes were compared with the 98 patients with MY-negative ALL. Patients were treated with the vincristine-doxorubicin-dexamethasone (VAD) regimens. RESULTS: Patients with MY-positive ALL were significantly older (median ages, 47 years vs. 33 years; P = 0.03), had a higher incidence of CD34 antigen expression (59% vs. 36%; P < 0.01), and a lower incidence of common acute leukemia antigen expression (50% vs. 71%; P < 0.01), serum alkaline phosphatase elevation (58% vs. 83%; P < 0.01), and thrombocytopenia at diagnosis (49% vs. 69%; P = 0.02). Myeloid marker positivity, as expected, was significantly higher in null cell ALL (82%), and significantly lower in mature B-cell ALL (17%) (P < 0.01). Forty-one of 64 MY-positive patients achieved complete remission (CR) after induction therapy compared with 76 of 98 patients MY-negative disease (CR rate 64% vs. 78%; P = 0.06). With a median follow-up of 45 months, no statistical differences were observed in remission duration or survival between MY-positive and MY-negative patients, overall, and within immunophenotypic subsets (T-cell vs. others), or among subgroups with single marker (CD13, CD14, CD33, CD34) positivity. The 3-year remission duration rates were 32% for MY-negative and 40% for MY-positive patients (P not significant), and 3-year survival rates were 26% and 31%, respectively (P not significant). CONCLUSIONS: With VAD therapy, myeloid marker positivity is not associated with significant differences in prognosis in adult ALL.

Adolescent↗
PubMed1995

Homoharringtonine therapy induces responses in patients with chronic myelogenous leukemia in late chronic phase.

Homoharringtonine (HHT) is a plant alkaloid with potent myelosuppressive activity and little toxicity when used in a continuous infusion schedule. The antileukemic efficacy of HHT has been shown in acute myeloid leukemia, but has not been investigated in chronic myelogenous leukemia (CML). Seventy-one patients with Philadelphia chromosome-positive (Ph+) CML in late chronic phase (time from diagnosis to therapy longer than 12 months) were treated with a continuous infusion of HHT at a daily dose of 2.5 mg/m2 for 14 days for remission induction and for 7 days every month for maintenance. The median number of courses given was 6 (range, 1 to 35) and 21 patients (30%) continue on treatment. Forty-two of 58 patients (72%) evaluable for hematologic response achieved a complete hematologic remission, and 9 (16%) had a partial hematologic remission. Twenty-two of 71 patients (31%) developed a cytogenetic response; it was major (Ph+ cells less than 35%) in 11 (15%) and complete (Ph+ cells 0%) in 5 (7%). Significant myelosuppression occurred in 39% of induction courses and 9% of maintenance courses. Fever or documented infection was present in 26% of induction courses and in only 8% of maintenance courses. Nonmyelosuppressive toxicity was minimal. Homoharringtonine produced hematologic remissions in the majority of patients with advanced chronic-phase CML. Cytogenetic response occurred in some patients without an association with myelosuppression, and these responses may be prolonged. Future studies investigating homoharringtonine in combination with other active agents in CML, such as interferon, are warranted.

Adult↗
PubMed1995

The breakpoint cluster region site in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Clinical, laboratory, and prognostic correlations.

BACKGROUND: The breakpoint site of the breakpoint cluster region (bcr) has been correlated with patient characteristics, with the disease phase, and with the prognosis of patients with chronic myelogenous leukemia (CML), but the findings remain controversial. METHODS: Appropriate restriction enzymes and the 3' and universal probes were used to map the breakpoint site by Southern blot analysis into 5' and 3' breakpoints and a breakpoint in zone 3 (or fragment 2) in 362 patients in different phases of CML (238 in early chronic phase, 69 in late chronic phase, 31 in accelerated phase, and 24 in blastic phase). Standard statistical methods were used to evaluate differences in characteristics and in prognosis by the breakpoint site. RESULTS: No correlation was noted between CML phases and breakpoint site. Among patients in the early chronic phase, thrombocytosis was significantly associated with the 3' breakpoint site (P = 0.02), whereas peripheral basophilia occurred more frequently with the 5' breakpoint site (P = 0.05). Other patient and disease characteristics were similar in frequency among the breakpoint-site subgroups. There was no difference in response to alpha-interferon therapy (186 patients treated) by the breakpoint site. Survival, dated from either referral to the authors' institution or from diagnosis, was not significantly different among patients with early chronic phase CML by the breakpoint site. However, patients with a 3' deletion tended to have a shorter survival. CONCLUSION: Determination of the breakpoint site by Southern blot analysis does not help to predict prognosis of patients with CML.

Chromosomes, Human, Pair 22↗
PubMed1995

Topotecan in chronic lymphocytic leukemia.

BACKGROUND: Topotecan is one of a new class of agents that targets topoisomerase I (Topo I) and stabilizes the DNA-topo1 complex, ultimately resulting in cell death. The rationale for the use of topotecan in chronic lymphocytic leukemia (CLL) is based on the finding that levels of Topo I are elevated in the lymphocytes of patients with this disease. METHODS: Twelve patients with CLL were treated with topotecan to assess its clinical efficacy; in addition, DNA-protein cross-linking was measured after exposure of the cells to topotecan, in an attempt to correlate potential anti-CLL effects with this parameter. The median age of the patients was 63 years; all had received prior therapy with fludarabine and four (33%) were resistant to fludarabine. Four patients (33%) had also received therapy with chlorambucil, and three of them were resistant to this agent. Seven patients (58%) were Rai stage I-II and five (42%) were Rai stage III-IV. Topotecan was given as a 30-minute infusion at a daily dose of 2 mg/m2 for 5 days, and courses were repeated monthly. Cells were obtained from the patients before treatment and exposed to 2 microM topotecan or control in vitro. In addition, cells were obtained from patients after they received the first dose of topotecan and protein-bound DNA was measured with the same technique. RESULTS: No patient responded to therapy with topotecan (95% confidence interval, 0-27%). Nonhematologic toxicity was mild and thrombocytopenia occurred in four of eight patients whose conditions could be evaluated. One patients died of myocardial infarction and another died of fungal pneumonia. DNA-protein cross-linking was detected in all nine patients whose cells were assessed in vitro, with levels of cleavable complex ranging from twofold to 7.5-fold that of the control cells. Only two of eight patients with evaluable conditions had increased cross-linking detectable in circulating cells after the first dose of topotecan, which was consistent with the drug's lack of effect in vivo. CONCLUSIONS: Although exposure of cells from patients with CLL to topotecan in vitro at 2 microM resulted in detectable protein-DNA cross-linking, this effect was not seen in patients who received a bolus dose of 2 mg/m2, and no remissions were noted in 12 patients.

Adult↗
PubMed1995

Advances in the biology and treatment of B-cell chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the western hemisphere. Diagnosis and staging of CLL are usually straightforward, but predicting an individual patient's prognosis is still a challenge. Cytogenetic abnormalities provide important prognostic information in CLL and may show its molecular heterogeneity. A search for oncogene abnormalities continues, although no consistent defects have been identified. New agents such as fludarabine produce high complete remission rates and have generated interest in earlier treatment as a first step in a potential cure. Fludarabine also makes autologous bone marrow transplant feasible as a consolidation therapy. Immunologic abnormalities and minimal residual disease persist in most patients in remission. Combining fludarabine with other active agents and devising effective postremission strategies may change the natural history of CLL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

A new form of long QT syndrome associated with syndactyly.

OBJECTIVES: The purpose of this study was to characterize a possible association between long QT syndrome and syndactyly. BACKGROUND: Long QT syndrome causes syncope and sudden death from ventricular arrhythmias. Syndactyly is a developmental disorder that causes webbing of the hands and feet. Both disorders can be inherited as isolated, autosomal dominant traits, but an association between them has not been established. METHODS: We identified three children with long QT syndrome, atrioventricular (AV) block and simple syndactyly. Phenotypic and laboratory data were obtained from families, attending physicians and medical records. RESULTS: All patients had bilateral cutaneous syndactyly and were diagnosed with long QT syndrome within the 1st 2 years of life. Structural heart disease, particularly a patent ductus arteriosus, was present in all three patients. Analysis of electrocardiograms showed marked prolongation of the QT intervals with rate-corrected QT intervals of 633, 628 and 680 ms, respectively. Transient AV block was also noted. Two of the three children died suddenly despite treatment with beta-adrenergic blocking agents and permanent pacing. CONCLUSIONS: We postulate that these children have a new form of long QT syndrome associated with syndactyly and a high risk of sudden death. The association of syndactyly with long QT syndrome may provide insight into the mechanisms underlying both disorders. Patients with syndactyly should be evaluated for the presence of long QT syndrome, and if it is found, aggressive treatment may be warranted.

Child, Preschool↗
PubMed1995

Treatment of Waldenstrom's macroglobulinemia resistant to standard therapy with 2-chlorodeoxyadenosine: identification of prognostic factors.

BACKGROUND: Few effective treatments are available for patients with Waldenstrom's macroglobulinemia that is resistant to standard therapies. We assessed the activity of 2-chlorodeoxyadenosine (2CdA) in patients with resistant macroglobulinemia in order to identify those most likely to benefit. PATIENTS AND METHODS: 2-chlorodeoxyadenosine was given to 46 consecutive patients with Waldenstrom's macroglobulinemia resistant to a combination of an alkylating agent and a glucocorticoid. Two courses were administered to outpatients at a dose of 0.1 mg/kg body weight per day for a 7-day continuous infusion using a portable pump through a central venous catheter. Responding patients were followed without further therapy. RESULTS: Twenty of 46 patients responded to 2CdA therapy (43%; 95 CI; 29 to 60%) with a significantly higher frequency of benefit among patients with disease relapsing off therapy (78%) or with primary resistant disease within the first year (57%) than in those with later phases of disease (22%). The median survival after treatment was 28 months and the median progression-free survival of responding patients was 12 months. The longest survival was measured in patients with primary refractory disease (projected median 36 months) and the shortest in those with disease in refractory relapse (median 13 months). CONCLUSION: 2-Chlorodeoxyadenosine is active against macroglobulinemic lymphoma resistant to standard regimens and most effective in patients with disease relapsing off treatment or during the first year of primary refractory disease. Little benefit was observed among patients with later phases of resistant disease who should receive alternative treatments.

Adult↗
PubMed1995

Retained sacral function in children with high level myelodysplasia.

To assess the preservation of sacral function despite denervation higher on the spinal cord in children with myelodysplasia, we examined 151 myelomeningocele patients presenting for urodynamic evaluation from 1980 to 1992 with a lesion at L3 or above on neurological examination. Of the 151 patients 70 (46%) had denervation of the external sphincter on initial evaluation and 81 (54%) had sacral sparing, that is normal or near normal electrical potentials of the external urethral sphincter and/or retained reflexic bladder activity regardless of the presence or absence of sacral reflexes. Of the 81 patients with sacral sparing 57 (70%) had detrusor-sphincter dyssynergia and 21 had synergy or denervation of the sphincter in association with retained detrusor reflexia. Whereas only 18% of children age 1 year or younger with retained sacral function had upper urinary tract deterioration on initial radiological studies (manifested by reflux or hydronephrosis), 57% had deterioration when evaluated after age 1 year. None of the patients without retained sacral function had evidence of upper urinary tract damage at younger than 1 year but 28% of those studied beyond age 1 year had changes. Patients with flaccid lower extremities can retain sacral function, which puts the upper urinary tract at risk of deterioration. Our results show that this risk increases with time.

Adolescent↗
PubMed1995

Cytogenetic and clinical correlates in AML patients with abnormalities of chromosome 16.

Abnormalities of chromosome 16 in AML include del(16q), inv(16) and t(16;16). These three groups have been categorized together and have been associated with high complete remission (CR) and survival rates following Ara-C-based chemotherapy. We have reviewed the 63 AML or MDS patients with an abnormality of chromosome 16 treated at MD Anderson Cancer Center (MDACC) over the past 18 years. Marked differences in survival and remission duration (RD) were noted between the inv(16) or t(16;16) patients and those with del(16q), whose outcome was no better than other M4 AML or MDS patients treated during the same period. Other differences characterizing del(16q) included a lack of CNS relapses, lower incidences of eosinophilia and M4 FAB subtype. Half the inv(16) patients had additional karyotypic abnormalities. The overall survival and remission duration for those patients were no different from those for patients with inv(16) alone, although the probability of remaining in first CR at 2 years was higher in the inv(16) alone group. There was no difference in overall survival for the 45 patients who received HDAC vs those who did not. The incidence of CNS relapse was, however, markedly reduced for the HDAC patients. Eosinophilia did not correlate with improved survival. We conclude that del(16q) confers a different prognosis from inv(16) and t(16;16) and for the purposes of prognostication or treatment recommendations should no longer be categorized with them. Additional karyotypic changes however, which accompany inv(16) in 50% of cases do not influence the overall outcome compared to patients with inv(16) alone.

Acute Disease↗
PubMed1995

Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: evaluation of 235 patients.

Williams syndrome (WS) is generally characterized by mental deficiency, gregarious personality, dysmorphic facies, supravalvular aortic stenosis, and idiopathic infantile hypercalcemia. Patients with WS show allelic loss of elastin (ELN), exhibiting a submicroscopic deletion, at 7q11.23, detectable by FISH. Hemizygosity is likely the cause of vascular abnormalities in WS patients. A series of 235 patients was studied, and molecular cytogenetic deletions were seen in 96% of patients with classic WS. Patients included 195 solicited through the Williams Syndrome Association (WSA), plus 40 clinical cytogenetics cases referred by primary-care physicians. Photographs and medical records of most WSA subjects were reviewed, and patients were identified as "classic" (n = 114) or "uncertain" (n = 39). An additional 42 WSA patients were evaluated without clinical information. FISH was performed with biotinylated ELN cosmids on metaphase cells from immortalized lymphoblastoid lines from WSA patients and after high-resolution banding analysis on clinical referral patients. An alpha-satellite probe for chromosome 7 was included in hybridizations, as an internal control. Ninety-six percent of the patients with classic WS showed a deletion in one ELN allele; four of these did not show a deletion. Of the uncertain WS patients, only 3 of 39 showed a deletion. Of the 42 who were not classified phenotypically, because of lack of clinical information, 25 patients (60%) showed a deletion. Thirty-eight percent (15/40) of clinical cytogenetics cases showed an ELN deletion and no cytogenetic deletion by banded analysis. These results support the usefulness of FISH for the detection of elastin deletions as an initial diagnostic assay for WS.

Abnormalities, Multiple↗
PubMed1995

Clinical and prognostic significance of trisomy 21 in adult patients with acute myelogenous leukemia and myelodysplastic syndromes.

Trisomy 21 is the second most common trisomy in patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, its clinical and prognostic significance is not known. We analyzed the records of 1187 consecutive patients with untreated AML or MDS. Thirty-seven (3.3%) had trisomy 21: four (0.3%) as the only cytogenetic abnormality and 33 (2.7%) with other cytogenetic abnormalities (-5 and/or -7 in 15, +8 in nine, t(15;17) in three, inv(16) in three, t(8;21) in one, and hyperdiploid with several other additional chromosomes in two). Twenty-eight patients had AML and nine MDS. No patients had megakaryocytic phenotype (M7), common in patients with constitutional trisomy 21 (Down's syndrome) and AML. Overall, 57% achieved complete remission (CR), with median CR duration of 39 weeks, and median survival of 31 weeks. When patients with additional cytogenetic abnormalities were compared to patients with similar abnormalities but no trisomy 21, their clinical features as well as their CR rate, CR duration and survival were similar, with or without trisomy 21. We conclude that trisomy 21 in AML typically presents in conjunction with other cytogenetic abnormalities, especially -5/-7 and +8 whose presence rather than the presence of +21 dictates the clinical outcome.

Adolescent↗
PubMed1995

High remission rate, short remission duration in patients with refractory anemia with excess blasts (RAEB) in transformation (RAEB-t) given acute myelogenous leukemia (AML)-type chemotherapy in combination with granulocyte-CSF (G-CSF).

A study was made to determine CR rate, response duration and survival in patients with RAEB or RAEB-t given AML-type chemotherapy, in particular the newer agents idarubicin and fludarabine. Eighty-five adults (58 RAEB-t, 27 RAEB) received either IA (idarubicin 12 mg/m2 daily on days 1-3, ara-C 1.5 g/m2 daily on days 1-4 CI), FA (fludarabine 30 mg/m2 daily on days 1-5, ara-C 2 g/m2 daily on days 1-5) or FLAG (FA + G-CSF 400 micrograms/m2 daily from day-1 until CR). IA was given exclusively to patients with better prognosis (as assessed by pretreatment karyotype), while FA and FLAG were given first to patients with worse and then to those with better prognosis. In remission, patients received lower doses of the same regimens for 6-12 months. The 85 patients comprise the largest reported series of RAEB or RAEB-t patients given AML-type chemotherapy. Their median age was 61 years, 33% had chromosome 5 or 7 abnormalities (-5/-7), and 55% were treated in laminar air flow rooms. The CR rate was 66%. While rates were highest in younger patients with a normal karyotype, CR rates in excess of 50% were also obtained in patients over age 60 (27/47; 57%) and in patients with -5/-7 (17/29; 59%). In 11 of the 14 cytogenetically abnormal patients in whom cytogenetic analysis was repeated at the time of CR, only normal metaphases were found. In the remaining 3 the number of abnormal metaphases was substantially reduced. However, the probability of continued CR was low (e.g. 452 +/- 0.08 at 12 months), and the only patients alive in CR beyond two years were patients under age 60 without -5/-7 and with RAEB-t. Survival probability was 0.35 +/- 0.05 at one year. Eight of 56 patients died in CR. While current AML-type chemotherapy can produce higher CR rates than is perhaps usually appreciated, in some patients with RAEB or RAEB-t (e.g. older patients with -5/-7) the brevity of the remissions and the risk entailed suggest that new post-remission therapies are needed to make this approach generally worthwhile.

Adult↗
PubMed1994

All-trans retinoic acid followed by chemotherapy for salvage of refractory or relapsed acute promyelocytic leukemia.

BACKGROUND: All-trans retinoic acid (ATRA) is effective in the treatment of relapsed or refractory acute promyelocytic leukemia (APL), but relapse is the rule if response is unmaintained. METHODS: Seventeen patients with APL were salvaged with ATRA at a dosage of 50 mg/m2/day for 3 months or until complete remission (CR) was achieved; idarubicin (12 mg/m2/day for 4 days) was added if blast plus promyelocyte count either was or reached > or = 10 x 10(3)/microliters. After CR was achieved, patients received three courses of idarubicin (12 mg/m2 daily for 3 days) followed by three courses of mitoxantrone (5 mg/m2 daily for 3 days) and etoposide (250 mg/m2 daily for 3 days). Maintenance was with 6-mercaptopurine and methotrexate. RESULTS: A CR was achieved in 14 patients (82%), the disease was refractory in 2 patients, and one patient died during induction. Three patients underwent allogeneic bone marrow transplant during CR. After a median follow-up of 26 weeks, six patients remain in CR. Median CR duration is 40 weeks (range 8-56+). Patients treated with ATRA plus chemotherapy in first salvage, when compared to a historic control group treated with chemotherapy alone, had a significantly better CR rate (87% vs. 57%; P = 0.04) and a lower induction death rate (7% vs. 29%; P = 0.08), resulting in longer median survival (26 vs. 17 weeks; P = 0.13). Four patients developed the "retinoic acid syndrome", which was fatal in one case. Three patients developed thrombotic events. CONCLUSIONS: ATRA followed by chemotherapy is effective treatment for patients with APL who relapse after conventional therapy, and it may be superior to chemotherapy alone.

Adolescent↗
PubMed1994

Lack of effect of 2-chlorodeoxyadenosine therapy in patients with chronic lymphocytic leukemia refractory to fludarabine therapy.

BACKGROUND: Fludarabine and 2-chlorodeoxyadenosine are nucleoside analogues that have proved effective in patients with chronic lymphocytic leukemia (CLL). Although their mechanism of action is thought to be similar, a small number of patients who do not respond to fludarabine do respond to 2-chlorodeoxyadenosine. The extent to which 2-chlorodeoxyadenosine is effective in patients who do not respond to fludarabine is not known, however. METHODS: We treated 28 patients with CLL refractory to fludarabine therapy with a continuous infusion of 2-chlorodeoxyadenosine at a daily dose of 4 mg per square meter of body-surface area for seven days. The treatment could be repeated monthly. The number of treatments ranged from one to five; patients who responded continued to receive treatment until the maximal response was achieved. RESULTS: Two patients (7 percent) had partial remissions, but no patients had complete remissions. One other patient had a substantial response but had residual thrombocytopenia. The rate of response in most affected organs was 20 percent, but anemia or thrombocytopenia rarely improved. Myelosuppression was frequent, and 65 percent of the courses of 2-chlorodeoxyadenosine therapy were accompanied by febrile episodes or infections. Ten patients died within 60 days of starting therapy with 2-chlorodeoxyadenosine; eight deaths were related to infection. The median platelet count at the start of 2-chlorodeoxyadenosine therapy in these 10 patients was 24,000 per cubic millimeter, as compared with 109,000 per cubic millimeter in the other 18 patients. Five patients were alive after a median follow-up of 24 months. CONCLUSIONS: Patients with advanced CLL refractory to fludarabine therapy are unlikely to benefit from treatment with 2-chlorodeoxyadenosine. Although 20 percent of the patients have some response, thrombocytopenia and anemia are rarely corrected and may be made worse by 2-chlorodeoxyadenosine therapy.

Adult↗
PubMed1994

2Chlorodeoxyadenosine therapy of patients with Waldenström macroglobulinemia previously treated with fludarabine.

BACKGROUND: Fludarabine monophosphate and 2Chlorodeoxyadenosine are nucleoside analogues with activity against Waldenström macroglobulinemia. However, it is not clear whether prior exposure to one analogue precludes response to the other compound. PATIENTS AND METHODS: Fourteen patients with Waldenström's macroglobulinemia and prior exposure to fludarabine were treated with two courses of 2chlorodeoxyadenosine. RESULTS: Three out of four patients that had previously responded to fludarabine and were relapsing from unmaintained remission, achieved a partial response with 2chlorodeoxyadenosine therapy. However, only one out of 10 patients with disease resistant to fludarabine responded to 2chlorodeoxyadenosine. CONCLUSIONS: 2chlorodeoxyadenosine may be effective in patients with Waldenström macroglobulinemia sensitive to fludarabine. However, this compound has limited activity for patients with disease resistant to fludarabine.

Aged↗