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Biomedical subjects

S O'Brien

Publications and source records attributed to S O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1994

Prognostic factors for survival in patients treated in phase I clinical trials.

BACKGROUND: Patients with advanced or metastatic cancer treated in Phase I clinical trials are considered to have a poor prognosis. Survival from first treatment in a Phase I trial was determined for 349 patients. Univariate and multivariate survival analyses were performed to determine whether potential prognostic factors and distinct risk groups could be identified. METHODS: Patients were identified retrospectively from a large data base of patients with advanced or metastatic cancer treated in Phase I clinical trials at the University of Chicago between February 1987 and October 1991. RESULTS: With a median follow-up of 29 months, 10% of patients were alive at the time of analysis. Twenty-nine percent were alive 1 year after the initiation of Phase I chemotherapy, and the median survival from first treatment in a Phase I study was 6.5 months. Multivariate analysis indicated that a better pretreatment performance status, a higher pretreatment serum albumin concentration, a lower pretreatment platelet count, no prior cisplatin chemotherapy, and a genitourinary or gynecologic cancer diagnosis were predictive of better survival. Three risk groups incorporating these five variables were identified, with median survivals of 12.7, 7.4, and 3.5 months for the good, intermediate, and poor risk groups, respectively. CONCLUSION: Patients treated in Phase I clinical trials have a median survival of 6.5 months, even though some patients have been treated at early (subtoxic and potentially subtherapeutic) dose levels. The results of this study may allow the identification of patients who are likely to survive long enough to contribute information on acute and cumulative drug-related toxicities and, possibly, tumor response.

Adult↗
PubMed1994

2-Chlorodeoxyadenosine therapy in patients with T-cell lymphoproliferative disorders.

Mature T-cell lymphoproliferative disorders comprise a heterogenous group of diseases for which there is no standard therapy. These disorders are uncommon, and are usually treated similarly to their B-cell counterparts, but with less success. Nucleoside analogues have proven effective in indolent B-cell disorders but have been less well explored in T-cell malignancies. We treated 22 patients with mature T-cell lymphoproliferative diseases with 2-chlorodeoxyadenosine (2-CDA) administered as a continuous infusion at a daily dose of 4 mg/m2 over 7 days. Nineteen of the patients had received prior therapy with a median number of prior regimens of three. Eleven patients had leukemia or large granular lymphocytosis, eight patients had mycosis fungoides, and three had T-cell lymphoma. Nine patients (41%) responded to 2-CDA. Four of the patients had responses that were complete remissions, and three of these four patients remain in remission at 23, 24, and 23 months. The only important toxic effects were fever or infection, seen during 38% of courses. In conclusion, 2-CDA appears to be an effective therapy in T-cell lymphoproliferative disorders and deserves wider evaluation in this subset of patients.

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

Antifungal prophylaxis during remission induction therapy for acute leukemia fluconazole versus intravenous amphotericin B.

BACKGROUND: Fungal infection is a frequent and often fatal complication in patients undergoing remission induction therapy for acute leukemia. Although candidiasis is the most common infection, mold infections are increasing in frequency. Fluconazole (FLU) is a new antifungal agent that has been used successfully to treat Candida infections and has modest activity against aspergillosis in animal models. Subtherapeutic doses of amphotericin B (AMB) have been considered effective as prophylaxis in these patients. This study was designed to compare the efficacy and toxicity of these agents as antifungal prophylaxis. METHODS: Adults with acute leukemia undergoing remission induction chemotherapy randomly were assigned to receive antifungal prophylaxis with AMB (0.5 mg/kg three times weekly) or FLU (400 mg daily). Trimethoprim-sulfamethoxazole was administered as an antibacterial prophylaxis. Prophylaxis was continued until the patient achieved complete remission or was treated for 8 weeks without antileukemic response. Prophylaxis was discontinued if the patient experienced a possible or proven fungal infection or a serious toxicity. RESULTS: Overall, 58% of the 36 patients assigned to AMB successfully completed prophylaxis compared with 80% of the 41 patients assigned to FLU (< 0.05). Proven, probable, or possible fungal infections occurred in 31% and 17% of the patients, respectively. The risk of discontinuing prophylaxis due to fungal infection or toxicity increased with time in the study and was significantly greater for AMB (P = 0.02). CONCLUSIONS: At the dose used in this study, AMB was no more effective and was more toxic than FLU for prophylaxis of fungal infections in patients undergoing remission induction chemotherapy for acute leukemia.

Acute Disease↗
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

Retinoblastoma protein expression is frequently altered in chronic lymphocytic leukemia.

The detection of abnormalities at the retinoblastoma (RB) locus by cytogenetics, Southern blot, and fluorescence in situ hybridization studies suggests that the RB gene has a role in chronic lymphocytic leukemia (CLL). To further study this role, we determined the level of RB protein present in the mononuclear cell fraction derived from peripheral blood or bone marrow samples from 74 patients with CLL, by Western blotting. Compared to similarly prepared samples from the peripheral blood of normal individuals, the level of RB in CLL cells was less than normal in 42% of patients, equal to normal in 22% of patients, and in excess of normal in 36% of patients. Regardless of whether the source of the sample was blood or marrow or if the patients were untreated or previously treated, similar rates of low, normal, and elevated RB levels were observed. RB protein in the CLL patient samples was never phosphorylated. RB levels showed no correlation with the lymphocyte doubling time or with proliferating cell nuclear antigen levels. Low RB levels could arise from genetic alterations of the RB gene or altered regulation of expression. To determine which was occurring, we stimulated the cells from 27 CLL patients in culture with either phytohemagglutinin or pokeweed mitogen in an attempt to induce RB expression and phosphorylation. Among patients with low levels of RB, expression was induced in 46% (6 of 13), and phosphorylation of RB was seen in 31% (4 of 13). Increased expression of phosphorylated RB was induced in 80% (4 of 5) of patients with normal levels of RB and in 78% (7 of 9) of patients with high levels of RB. This study demonstrates that absent RB expression occurs commonly in patients with CLL. Intrinsic abnormalities of the RB gene may be present in those patients with low levels of RB that could not be stimulated by mitogens, while regulatory abnormalities located in trans to the RB gene may occur in the other half. Given the importance that RB levels play in other cancers, the prognostic implication of low RB levels should be studied in CLL.

Blotting, Western↗
PubMed1994

Philadelphia-chromosome-positive adult acute lymphocytic leukemia: characteristics, treatment results, and prognosis in 41 patients.

BACKGROUND: Philadelphia-Chromosome-positive (Ph-positive) acute lymphocytic leukemia (ALL) is associated with poor outcome in children as well as in adults. We report our experience in patients with Ph-positive ALL and review their clinico-laboratory characteristics, response to different therapies, and overall prognosis. PATIENTS AND METHODS: Since 1980, 41 newly diagnosed patients with Ph-positive ALL were referred to our service. In addition to confirmation of their diagnosis by morphologic studies of bone marrow aspiration and biopsy specimens, patients underwent cytogenetic, immunophenotypic, and molecular studies. Thirty-five patients received vincristine-Adriamycin-dexamethasone (VAD) or cyclophosphamide (CVAD) induction regimens, and 6 patients were treated with other combinations. Thirty-seven patients received salvage therapy that included VAD, high-dose cytosine arabinoside (ara-C)-containing regimens, methotrexate-asparaginase, and high-dose chemotherapy with autologous or allogeneic bone marrow transplantation (BMT). RESULTS: The 41 patients were among 334 patients with ALL (12%) seen during that same period. Patients with Ph-positive ALL were older and had a significantly lower incidence of anemia and a higher incidence of peripheral leukocytosis, FAB L2 (French-American-British) morphology, common acute lymphocytic leukemia antigens (CALLA), and CD34 marker positivity. With induction chemotherapy, 23 of 41 Ph-positive ALL patients (56%) achieved complete remission, and their median survival and remission duration were 11 months and 9 months, respectively. Thirteen of 31 Ph-positive ALL patients (42%) achieved complete response with high-dose ara-C regimens during salvage therapy. CONCLUSIONS: In our experience, patients with Ph-positive ALL are usually older, have FAB L2 morphology, and are CALLA-positive and CD34-positive. These patients have a poor prognosis when treated with conventional approaches with lower overall complete response rate, shorter remission duration, and shorter survival. There appears to be a selective sensitivity to high-dose ara-C in these patients that suggests a possible role of this agent as part of early consolidation or induction regimens.

Adult↗
PubMed1994

The role of fludarabine in hematological malignancies.

Fludarabine monophosphate, a synthetic nucleoside analog, has been shown to have considerable activity in a number of lymphoid malignancies. In chronic lymphocytic leukemia the response rates can exceed 70% with a considerable proportion of complete remissions being attained. These rates are markedly superior to earlier therapies with which complete remission was uncommon. It also has significant activity in previously treated patients for whom effective salvage regimens were unsatisfactory. In addition, fludarabine shows substantial activity in low grade non-Hodgkin's lymphoma, both as initial treatment and as salvage therapy. Fludarabine is effective in Waldenstrom's macroglobulinemia and is active in other low grade lymphoid malignancies. Major toxicities are reversible myelosuppression and depletion of T lymphocytes. The use of fludarabine in hematological malignancies will be reviewed, with reference to its mode of action and future use in combination therapies.

Adult↗
PubMed1994

A non-invasive optical technique for intrapartum fetal monitoring: preliminary clinical studies.

A relatively new optical method based on near infra-red spectroscopy was evaluated in preliminary clinical trials for noninvasive intrapartum fetal monitoring. The measurements were performed using mainly the light reflection mode of monitoring. Continuous monitoring of changes in the concentrations of oxygenated and deoxygenated haemoglobin and thus changes in total haemoglobin concentration in the fetal brain was achieved. It was found that uterine contractions can influence in a distinctive manner the near infra-red derived cerebral haemoglobin concentration changes in the fetus. The results indicate that near infra-red spectroscopy could offer a non-invasive real-time monitoring method for in vivo monitoring of blood oxygenation in the fetal brain. We conclude that this technique may be useful for intrapartum fetal monitoring and in predicting fetal cerebral hypoxia.

Brain Chemistry↗
PubMed1994

Fludarabine--present status and future developments in chronic lymphocytic leukemia and lymphoma.

BACKGROUND: Fludarabine monophosphate (fludarabine) is an adenine nucleoside analogue active in indolent lymphoproliferative diseases which has an increasing role in studies incorporating combinations of agents which exploit biochemical modulation, inhibition of DNA repair, and radiosensitizing effects. PATIENTS AND METHODS: Patients with lymphoma and chronic lymphocytic leukemia (CLL) treated at the M. D. Anderson Cancer Center (MDACC) and reports in the literature form the basis of this report. RESULTS: CLL has traditionally been treated with alkylating agents and corticosteroids. In this study, fludarabine has shown marked cytoreductive ability in both previously treated patients and untreated patients. In the former group, there has been a 55% response rate in 374 patients, and 79% in the untreated CLL group. Fludarabine has also been very active in the management of low-grade lymphomas, with two-thirds of patients with follicular lymphoma and half of those with other indolent lymphomas responding. Waldenstrom's macroglobulinemia is also sensitive to the effects of fludarabine. Combination regimens were developed incorporating the substantial effectiveness of fludarabine and mitoxantrone where in the previously treated low-grade lymphoma group 25 of 28 patients (89%) responded. Fludarabine has the effect of increasing the triphosphate form of cytosine arabinoside in acute and chronic leukemic cells. This modulation has now been translated into therapy for acute leukemia and combined with cisplatinum in refractory CLL. Fludarabine inhibits DNA repair and enhances cross-linking of DNA by cisplatinum. The combination of fludarabine, ara-C, and cis-platinum is now being used in refractory CLL. Fludarabine is a radiation sensitizer, inhibiting repair of DNA damage. Studies are ongoing with this combination. CONCLUSIONS: Fludarabine is a potent molecule with a wide range of biochemical effects. Optimal use of this drug alone and in combination is continuing to be explored.

Adrenal Cortex Hormones↗
PubMed1994

Chronic myelogenous leukemia.

The Ph chromosome, the abnormality characteristic of chronic myelogenous leukemia, was discovered in 1963. However, the events responsible for the pathogenesis and transformation to accelerated and blastic phases are still unknown at the molecular level and are subjects of ongoing research. The positive outcome in a subset of patients with interferon therapy and the potential for cure with bone marrow transplantation have evoked controversy regarding the best approach for different groups of patients according to prognostic characteristics. At the same time, new therapies with promising results are being developed, both in the setting of chemotherapy and biologic therapy and in bone marrow transplantation. Homoharringtonine chemotherapy, the use of matched unrelated donors for bone marrow transplantation, and new modalities of purging for autologous bone marrow transplantation are some examples. Sensitive molecular techniques that allow for the detection of small numbers of bcr-abl-positive hematopoietic cells may provide new means of assessing the results of current and future therapies.

Antibodies, Monoclonal↗
PubMed1994

Acute lymphocytic leukaemia in the elderly: characteristics and outcome with the vincristine-adriamycin-dexamethasone (VAD) regimen.

To analyse the pretreatment characteristics, response to therapy, and overall prognosis of elderly patients with acute lymphocytic leukaemia (ALL), 268 consecutive adults with newly-diagnosed ALL who received the vincristine-adriamycin-dexamethasone (VAD) regimens were reviewed. Pretreatment characteristics, response to VAD therapy, and overall outcome were analysed in patients 60 years or older, and compared to younger patients. Fifty-two patients (19%) were 60 years or older. Compared with younger patients, elderly patients with ALL had a significantly worse performance status at presentation (P < 0.001); higher incidences of FAB L2 morphology (P = 0.03), thrombocytopenia (P < 0.01), hypoalbuminaemia (P < 0.001) and renal dysfunction (P = 0.03); and trends for worse anaemia (P = 0.06) and a higher rate of myeloid markers positivity (P = 0.06). With VAD induction therapy, elderly patients had a lower CR rate than younger patients following two induction courses (CR rate 58% v 82%; P < 0.01), and overall (CR rates 65% v 90%; P < 0.01). The response rate to VAD chemotherapy, however, appeared superior to the 30-35% CR rates reported from other series in elderly ALL patients. The lower CR rate was due to both higher induction mortality (P = 0.02) and more resistant disease (P < 0.01). The long-term CR rate was 20% in elderly patients achieving CR, but the overall survival was poor (< 10% at 3 years). There were strong associations between older age and other poor prognostic features. However, multivariate analyses identified older age to be an independent poor prognostic factor for response to chemotherapy. In summary, elderly patients with ALL have an appreciable CR rate with the VAD regimens. Patients achieving CR may have durable remissions. The myelosuppression-associated mortality in both remission induction and maintenance may be reduced with the addition of growth factors in both treatment phases, and by using standard maintenance therapy without consolidation-intensification phases.

Age Factors↗
PubMed1994

Primary therapy of Waldenström's macroglobulinemia with 2-chlorodeoxyadenosine.

PURPOSE: To assess the activity of 2-chlorodeoxyadenosine (2CdA) as primary therapy for patients with Waldenström's macroglobulinemia. PATIENTS AND METHODS: 2CdA was given to 26 consecutive, previously untreated and symptomatic patients with Waldenström's macroglobulinemia. 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 up without further therapy and were scheduled to receive two additional treatments with 2CdA on disease relapse. RESULTS: Twenty-two of 26 patients responded to the 2CdA therapy (85%; 95% confidence interval [CI], 65% to 96%), including three patients who achieved a complete response and 19 patients who had a partial response. Treatment was well tolerated, with no acute hematologic toxicity. A marked and sustained reduction of CD4+ lymphocytes occurred in all patients and may have contributed to a fatal infection with disseminated herpes simplex in one patient. With a median follow-up of 13 months, five patients have relapsed and all re-treated patients have responded again to 2CdA. CONCLUSION: 2CdA is highly active in previously untreated patients with Waldenström's macroglobulinemia. A limited program of treatment induced responses of good quality and long duration in more than 80% of patients.

Adult↗
PubMed1994

Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor.

PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF) administered before, during, and after fludarabine plus cytarabine (ara-C; FA) chemotherapy affected complete response (CR) rate, infection rate, blood count recovery, or survival in patients with newly diagnosed acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). PATIENTS AND METHODS: A total of 112 patients with newly diagnosed AML (n = 69) or MDS (n = 43) received G-CSF 400 micrograms/m2/d 1 day before (presenting WBC count < 50,000/microL) and/or during (all patients) fludarabine 30 mg/m2/d and ara-C 2 g/m2/d for 5 days (FLAG). G-CSF continued until a CR was achieved. Results were compared with those in 85 newly diagnosed patients (54 AML, 31 MDS) previously treated with FA without G-CSF. RESULTS: Patients in both groups were relatively old (median age of all patients, 63 years), and were likely to have prognostically unfavorable cytogenetic abnormalities (36% had abnormalities of chromosomes 5 and 7 [-5/-7]). G-CSF accelerated recovery to > or = 1,000 neutrophils (P < .0001; median, 34 days for FA, 21 days for FLAG), but logistic regression provided no evidence that the CR rate was higher with FLAG than with FA (P = .50), with unadjusted CR rates of 63% and 53%, respectively. This may reflect relatively high rates of death before neutrophil recovery in both groups. Rates of infection were similar in both groups. The follow-up duration in remission is short, and much of these data remain censored. To date, survival is similar with FA and FLAG. CONCLUSION: On average, G-CSF before, during, and after FA had no effect on CR or infection rates in this population, in which elderly patients and poor prognostic factors were prevalent. The use of FA and laminar airflow rooms rather than more usual therapy needs to be considered when analyzing the results.

Aged↗
PubMed1994

Clinical experience with fludarabine in leukaemia.

Fludarabine (Fludara) is a new purine analogue that was first entered into clinical trials in 1982. Results of initial studies with high dosages (> 96 mg/m2/day for 5 to 7 days) of fludarabine in acute leukaemia showed significant cytoreductive activity but a high incidence of severe irreversible neurotoxicity. The results of subsequent studies with lower dosages of 25 to 30 mg/m2/day for 5 days in chronic lymphocytic leukaemia (CLL) and low grade lymphomas have shown this regimen to be effective and safe, with almost no significant neurotoxicity. At present, the major role of fludarabine in leukaemia is in the management of CLL. In previously treated patients with CLL, responses are obtained in more than 50% of patients, with two-thirds of those responses being complete remissions according to the National Cancer Institute Working Group (NCIWG) criteria for complete response and partial response. The major causes of morbidity associated with fludarabine in CLL are infections and febrile episodes. These occur more frequently in previously treated patients and those with advanced stage of disease. Myelosuppression is dose limiting and a small proportion of patients with CLL develop moderate to severe and sometimes protracted myelosuppression. Administration of combined fludarabine and cytarabine (cytosine arabinoside; ara-C) alone (FA regimen) or together with granulocyte colony-stimulating factor (FLAG regimen) produced high response rates in previously treated refractory patients with acute leukaemia and previously untreated patients with acute myelogenous leukaemia or myelodysplastic syndrome. The wide range of biochemical and biological activities of fludarabine suggests that it will have an expanding role in future combinations in the treatment of both acute and chronic leukaemias.

Antineoplastic Agents↗
PubMed1994

Phase I trial of a genetically engineered interleukin-2 fusion toxin (DAB486IL-2) as a 6 hour intravenous infusion in patients with hematologic malignancies.

DAB486IL-2 is a recombinant fusion toxin, created by replacement of the receptor binding domain sequences of the diphtheria toxin gene with the sequences for human interleukin-2 (IL-2). It selectively binds to and intoxicates cells expressing the high-affinity IL-2 receptor. A total of 17 patients with refractory hematologic malignancies were entered in a phase I study of DAB486IL-2, administered as a 6 hour continuous intravenous infusion on days 1, 2, 8, 9, 15, and 16 of each 28 day cycle. Cohorts of 3 to 6 patients were treated with escalating doses. The starting dose was 0.1 mg/kg/day with increments of 0.1 mg/kg/day per dose level up to 0.3 mg/kg/day. Significant adverse effects included transient asymptomatic elevation of liver transaminases, hypersensitivity, anemia, thrombocytopenia, fever, and creatinine elevation. A partial response of approximately nine months duration was observed in a patient with small cell lymphocytic non-Hodgkin's lymphoma, previously refractory to high-dose chemotherapy and autologous bone marrow transplantation. The observance of antitumor activity in a patient highly refractory to chemotherapy suggests that DAB486IL-2 may have efficacy in selected patients whose malignant cells express the IL-2 receptor.

Adult↗
PubMed1994

Leukemia cutis in acute promyelocytic leukemia: report of three cases after treatment with all-trans retinoic acid.

Acute promyelocytic leukemia (APL) is a distinct form of acute myelogenous leukemia characterized by an abundant number of abnormal progranulocytes, a severe coagulopathy and a distinct chromosomal abnormality t(15;17). Recently all-trans retinoic acid (ATRA) has been shown to induce complete remissions in APL. We report three patients with APL treated with ATRA, who at the time of relapse had leukemic infiltration of the skin (leukemia cutis), a manifestation which we had not seen previously in over 60 patients with APL treated with chemotherapy alone and has only rarely been reported in the literature. We hypothesize that ATRA treatment for APL may be associated with an increased incidence of extramedullary disease at the time of relapse, which may be mediated through an increase in expression of adhesion molecules. Careful observation for extramedullary relapses in patients treated with ATRA for APL will be needed to confirm our observation.

Adult↗