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A Atra

Publications and source records attributed to A Atra.

At least 19 recordsLinked to original sources
PubMed2004

Acute neurotoxicity in children with advanced stage B-non-Hodgkin's lymphoma and B-acute lymphoblastic leukaemia treated with the United Kingdom children cancer study group 9002/9003 protocols.

We reviewed the pattern of acute neurotoxicity in children with B-non-Hodgkin's lymphoma (B-NHL) and B-acute lymphoblastic leukaemia (ALL) treated with the UKCCSG 9002/9003 protocols. Among 175 patients, 21 (12%) developed acute neurotoxicity: 9002 protocol (n=11/112) and 9003 (n=10/63). There were 20 boys and the median age was 10 years. Patients with neurological symptoms due to other causes were excluded. Acute neurological symptoms developed following induction chemotherapy in 7 patients, or after a more intensive course of chemotherapy containing high-dose methotrexate (n=14). Nine patients required their chemotherapy to be altered because of the acute neurotoxicity. One patient died of cerebral haemorrhage but none of the remaining six deaths was attributed to acute neurotoxicity. We conclude that acute neurotoxicity is common in children treated with the 9002/9003 protocols and tends to be transient. Intrathecal and systemic chemotherapy including high-dose methotrexate is probably the most common predisposing factor. Modification of subsequent chemotherapy is not invariably necessary.

Acute Disease↗
PubMed2003

Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease.

Thalidomide was used to treat acute (n=21) or chronic (n=59) graft-vs-host disease (GVHD) in 80 haematopoietic stem cell allograft recipients after failure to respond to the combination of cyclosporine and corticosteroids with or without other agents. The median time to onset of acute GVHD was 11 days, and thalidomide was started at a median of 48 days post transplant. In addition to corticosteroids and cyclosporine, 13 patients had also received other agents before thalidomide. None of the patients responded and all died of acute GVHD. For chronic GVHD (limited in 13, extensive in 46), thalidomide was started at a median of 385 days post transplant. In addition to corticosteroids and cyclosporine, 34 patients received azathioprine concomitantly. In all patients, thalidomide was added to the ongoing immunosuppressive regimen. The median duration of therapy with thalidomide was 60 days (range, 11-1210; <2 weeks in 11). In total, 13 patients (22%) had complete response, eight (14%) partial response and 38 (64%) no response. Response rates were comparable for limited (39%) and extensive (33%) chronic GVHD. At a median of 53 months, 19 patients are alive, 13 without evidence of chronic GVHD. Survival was significantly better in patients who responded to thalidomide. The principal causes of death were progressive chronic GVHD (n=29) and relapsed leukaemia (n=7). In conclusion, thalidomide has no activity in acute GVHD, but has some activity in chronic GVHD in combination with other agents.

Acute Disease↗
PubMed2001

Outcome of relapsed or refractory childhood B-cell acute lymphoblastic leukaemia and B-cell non-Hodgkin's lymphoma treated with the UKCCSG 9003/9002 protocols.

Twenty-six children with B-cell acute lymphoblastic leukaemia (B-ALL) or Murphy Stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) progressed or relapsed after first-line therapy with a short, intensive multiagent chemotherapy regimen [United Kingdom Childhood Cancer Study Group (UKCCSG) 9003] (n = 62) or a slightly less intensive regimen (UKCCSG 9002) (n = 112). Eight patients (4.6%) never achieved complete remission (CR) and 18 (10.3%) relapsed. Second-line therapy resulted in remission for eight patients (30%). All patients initially treated with the 9003 protocol died. Three patients (11.5%) in the 9002 group, including one who never achieved CR in the primary site, are alive after second-line therapy. This study confirms that the prognosis of relapsed or refractory B-ALL/B-NHL is poor and exceptionally so if relapse occurred less than 6 months from diagnosis. High-dose therapy with stem cell rescue was used in only seven patients; its role needs to be studied further.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Melphalan/TBI is not more carcinogeneic than cyclophosphamide/TBI for transplant conditioning: follow-up of 725 patients from a single centre over a period of 26 years.

As there is concern regarding the high carcinogenic potential of melphalan (Mel), 725 patients with haematological malignancies who received allogeneic (n = 714) or syngeneic (n = 11) transplants over the last 26 years were followed-up to evaluate if melphalan was more likely to result in secondary malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ninety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients developed non-haematological SMN. Median time to develop a SMN was 7 years (range 2-17 years). Age-adjusted rate was significantly higher than in the general population (observed 12 expected 1.2, risk 10; P < 0.0001). The cumulative overall risk of developing a SMN at 2, 5, 10 and 15 years post transplant was 0.4% (95% CI 0.1-2.6%), 1.7% (95% CI 0.6-4.4%), 6.4% (95% CI 2.8-10.8%) and 6.6% (95% CI 3.4-12.4%), respectively. Even though age-adjusted rates were higher than the general population melphalan/TBI was not associated with higher age-adjusted risk than Cy/TBI (increased risk 7.9 vs 11.4; P = NS). The cumulative overall risk of SMNs was not different with CY/TBI or Mel/TBI (8/393 vs 4/363; 10 year risk 4.4%, 95% CI 1.8-10.6 vs 8.4%, 95% CI 2.9-22.9; P = NS). The risk was significantly higher with use of additional cranial or cranio-spinal irradiation (17.5% vs 2.7% at 10 years; P = 0.0241). Transplants for acute lymphatic leukaemia resulted in a higher incidence of SMNs than did transplants for other diseases (ALL: 17.4%, 95% CI 6.3-42.6%; other diseases: 3.4% (95% 1.3-8.5%, P = 0.0469). The risk of SMN for patients with chronic GVHD was 8.4% (95% CI 3.7-18.7%) as compared to 3.5% (95% CI 1-11.1%) for patients without chronic GVHD (P = NS). No factor was associated with independently increased risk in multivariate analysis. Use of melphalan and TBI for transplant conditioning does not appear to be associated with higher risk of second malignant neoplasms than cyclophosphamide and TBI.

Adolescent↗
PubMed2000

Autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission - long-term follow-up.

From 1984 to 1996, 31 consecutive children without sibling donors, aged 5-19 years (median 8) with acute lymphoblastic leukaemia (ALL) in second complete remission (CR), received unpurged autologous bone marrow transplantation (ABMT) after melphalan and single fraction total body irradiation (TBI). ABMT was performed using fresh unmanipulated marrow harvested after standard reinduction and consolidation therapy 2-11 months (median 5) after relapse. With a median survival of 2.9 years the probability of survival for all patients in continuing second CR was 45.1% (95% CI, 24%-62%) after 5 years. Regimen-related and non-leukaemia mortality was 7% (95% CI, 2%-26%). The longest time to second relapse from ABMT was 3.1 years. Pituitary and gonadal dysfunction requiring hormonal replacement therapy occurred in the majority of long-term survivors. Twelve patients developed cataracts. ABMT with melphalan/single fraction TBI has proved an effective anti-leukaemia treatment with low regimen-related mortality but significant long-term morbidity. The current approach of allogeneic BMT from an unrelated donor when no sibling donor is available, following conditioning with cyclophosphamide/ fractionated TBI has resulted in a reduced relapse rate and improved short-term overall survival in the treatment of relapsed childhood ALL. However, long-term results are awaited.

Adolescent↗
PubMed2000

Improved outcome in children with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL): results of the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol.

From July 1990 to March 1996, 112 children with stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) with up to 70% FAB L3-type blasts (n = 42) in the bone marrow without central nervous system (CNS) disease were treated on the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol (identical to the French LMB 84). The median age was 8.3 years. There were 81 boys and 31 girls. According to the extent of the primary disease, patients were sub-staged into three groups: IIIA with unresectable abdominal tumour (n = 39); IIIB with abdominal multiorgan involvement (n = 57) and IIIX with extra-abdominal primary lymphoma often presenting as pleural effusion (n = 16). Univariate and multivariate analyses were carried out to evaluate the prognostic significance of lactate dehydrogenase (LDH) level at diagnosis, the sub-stage and the time to achieve complete remission (CR). With a median follow up of 48 months (range 12-92), the overall and event free survival (EFS) is 87% (95% confidence interval (CI) 79.2-92.1 %) and 83.7% (95% CI 76.3-89.2%) respectively. Six patients (5.4%) never achieved CR, of whom one is alive following high-dose therapy. Eight patients (7.1%) relapsed after achieving CR, three are alive after second-line therapy. There were three early toxic deaths (2.7%), mainly from infection, and one late death from a second cancer. There was no significant difference in EFS according to LDH level at diagnosis, the sub-stage or the time to CR. This study confirms the overall good prognosis and low rate of toxic deaths in patients with advanced B-NHL treated with this intensive regimen. No significant difference in EFS according to the sub-stage, the time to achieve CR or LDH level at diagnosis making it difficult to identify a group that should not receive intensive therapy.

Adolescent↗
PubMed1999

Local therapy and other factors influencing site of relapse in patients with localised Ewing's sarcoma. United Kingdom Children's Cancer Study Group (UKCCSG).

Relapse patterns have been documented in 191 children with localised Ewing's sarcoma treated with the United Kingdom Children's Cancer Group (UKCCSG) Ewing's Tumour regimen ET2. All received chemotherapy comprising ifosfamide, vincristine, doxorubicin and actinomycin D. Local treatment modality was excision and or radiotherapy depending on tumour site and response to primary chemotherapy. Although not strictly comparable, due to the clinical indications used for each modality, local relapse rates were very low and were similar, irrespective of the type of local treatment modality: radiotherapy (3/56), surgery (7/114) or a combination (0/20). Combined relapse (local + distant) rates were similarly low irrespective of the type of local therapy: radiotherapy (4/56), surgery (4/114) or a combination (0/20). Overall survival was lower in females (P = < 0.04), older children (P = < 0.002) and those with primaries at sites other than long bones (P = < 0.02). It is concluded that with effective intensive chemotherapy combined with either radiotherapy or surgery, local control in this study was excellent at sites other than the pelvis. Preventing distant relapse, predominantly to lung and bone, remains the major challenge.

Adolescent↗
PubMed1999

Acute erythroid leukemia (M6): outcome of bone marrow transplantation.

Erythroid leukemia is an uncommon form of acute myeloid leukemia (AML) which has previously been associated with a poor prognosis. We present the outcome of 27 patients with AML-M6 (19 de novo and 8 secondary) treated with intensive regimens including bone marrow transplantation (BMT). In the de novo group, median age was 30 years (2-72); 5 cases were under 15 years. Remission rate after induction chemotherapy was 95%. Consolidation in those achieving remission with BMT was 82%. Transplant related mortality was 36%. Median survival for de novo M6 was 2.9 years which was not significantly different to matched controls with AML (non M6). Overall relapse rate was 35%. In contrast, patients with secondary disease had a poor prognosis with lower remission rates (57%) and higher relapse rates (75% of those achieving remission after induction chemotherapy). In our series, the prognosis of patients with AML-M6 was most closely related to age and disease status at presentation (de novo or secondary). The disease is sensitive to AML induction regimens and long-term survival can be achieved with BMT in first complete remission.

Adolescent↗
PubMed1999

Outcome of biphenotypic acute leukemia.

BACKGROUND AND OBJECTIVE: Although biphenotypic leukemia is now a defined entity, outcome of this rare form of acute leukemia has not been well documented. We present the first comprehensive study analyzing induction and consolidation therapy of biphenotypic leukemia and correlate outcome to prognostic factors. DESIGN AND METHODS: In this retrospective study, the incidence of biphenotypic leukemia was found to be 3.6% from 693 adult and pediatric acute leukemias referred to our center for treatment over the last 8 years. Of these, 15 were B-lymphoid/myeloid, 8 were T-lymphoid/myeloid, one was T/B lymphoid and one had trilineage differentiation. RESULTS: Induction of remission in de novo cases was achieved in 70% of patients and relapse of disease occurred in 15%. The use of combined lymphoid and myeloid drugs for induction resulted in a high incidence of early deaths (25%). The overall probability of survival at 2 years was 39.4%. Patients with secondary disease had a uniformly poor outcome with low remission rates and high relapse rates. INTERPRETATION AND CONCLUSIONS: Prognosis was most strongly related to the presence of the Philadelphia chromosome (p=0.03) and age under 15 years (p=0.01). We conclude that patients with biphenotypic leukemia should have risk stratification with treatment tailored to their prognostic factors.

Acute Disease↗
PubMed1998

A limited role for VEEP (vincristine, etoposide, epirubicin, prednisolone) chemotherapy in childhood Hodgkin's disease.

The VEEP regimen (vincristine, etoposide, epirubicin, prednisolone), with or without involved field radiotherapy, has been shown to be an effective treatment in adult Hodgkin's disease. In an attempt to avoid the late sequelae of both alkylating agents and radiotherapy this regimen has been studied in a series of 54 children and young adults. Early analysis suggested that the relapse rate was higher with VEEP than with standard alkylating agent-based regimens. Sufficient follow-up has now been achieved to evaluate the likelihood of sustained remission following second-line treatment and therefore the overall long term survival with this treatment approach. The 5-year Overall Survival (OS) and 5-year Progression Free Survival (PFS) for patients with stage I-III disease was 93% and 82% respectively. However, the 5-year OS and PFS for stage IV patients was only 44% and 50%, respectively. Of 13 patients who were initial treatment failures on VEEP, 7 of whom had advanced disease, only 6 were salvaged with second-line therapy. 8 of 33 who attained a complete response (CR) relapsed and there were 2 relapses in those achieving a partial response (PR) (n = 8). All those relapsing from CR/PR were salvaged by second-line alkylating agent chemotherapy +/- radiotherapy, +/- high dose chemotherapy. In conclusion, patients with stage I-IIIA, non-bulky disease, the moderately high relapse rate did not adversely affect the overall high cure rate, although VEEP failures were subjected to a high total treatment burden. VEEP alone is inadequate in patients with stage IV disease, bulky mediastinal disease in/or those with B symptoms in whom there is a high primary failure rate and relatively poor results with second line therapy.

Adolescent↗
PubMed1998

Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non-Hodgkin's lymphoma (B-NHL)--results of the UKCCSG 9003 protocol.

From June 1990 to February 1996, 35 patients with B-cell acute lymphoblastic leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to 16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide, vincristine, daunorubicin, high-dose methotrexate (COPADM) and etoposide/high-dose cytarabine (CYVE) with frequent intrathecal (i.t.) triple therapy (methotrexate, cytarabine and hydrocortisone). Cranial irradiation (24 Gy in 15 fractions) was recommended in patients with overt CNS disease. One patient with Wiskott-Aldrich syndrome was withdrawn after entry and has been excluded from the analysis. Ten patients (16%) have relapsed (CNS, four; BM, two; combined CNS and BM, three; and jaw, one) 4-11 months after diagnosis and two patients never achieved complete remission (CR). All have died. In seven of the patients who relapsed, treatment had been modified or delayed because of poor clinical condition. Seven patients (11%) died of toxicity 11 days to 4 months after diagnosis. The cause of death was sepsis (n = 5) or sepsis with renal failure (n = 2). With a median follow-up of 3.1 years from diagnosis (range 9 months to 6.3 years), 43 patients (69%) survive in CR. This study confirms the effectiveness of this regimen with regard to the relapse rate (16%), although the rate of toxic death is of concern.

Adolescent↗
PubMed1998

Conservative management of follicular non-Hodgkin's lymphoma in childhood.

Among 447 children with non-Hodgkin's lymphoma (NHL) on the childhood U.K. registry, seven children with follicular (NHL) were identified. Four were male and their age ranged from 4.25 to 13.5 years (median 7.5); all had localized disease, Murphy's stage I (n = 4) and II (n = 3). Sites involved at presentation were cervical lymph nodes and tonsils (n = 5), ileum (n = 1) and parotid gland (n = 1). Three had complete surgical excision only and four had complete (n = 1) or incomplete excision (n= 3) followed by a short multi-agent chemotherapy regimen (UKCCSG 9001 protocol). With a median follow-up of 1.5 years (range 0.25-5 years) from diagnosis, six are alive in complete remission (CR) including three who had no chemotherapy. These results confirm previous reports that follicular lymphomas in children are rare (1.5%) and tend to be localized at presentation. Their rarity makes it difficult to produce guidelines about treatment, but in localized cases a period of non-intervention may be justified.

Antineoplastic Agents↗
PubMed1998

Metastatic cardiac osteosarcoma--imaging features.

There are several reports of osteosarcoma metastases to the heart. A rare case of a metastatic osteosarcoma to the endocardium of the left atrium in a 17 year old patient is described. The radiological features are discussed in detail.

Adolescent↗
PubMed1997

High-dose busulphan/melphalan with autologous stem cell rescue in Ewing's sarcoma.

Eighteen patients with poor risk Ewing's sarcoma (including 11 patients with metastatic disease at presentation) received consolidation therapy of busulphan and melphalan with autologous stem cell rescue. There were nine females. The median age at diagnosis was 14.2 years (range 2.75-30 years). There was one early death due to cytomegalovirus pneumonitis. One patient developed a single generalised convulsion during busulphan therapy. Severe renal toxicity was not encountered. One patient developed veno-occlusive disease of the liver (VOD) which eventually resolved. With a median follow up of 2 years, 13 patients survive including six with initial metastatic disease. We conclude that high-dose busulphan/melphalan is well-tolerated and should be evaluated for efficacy in a larger series of patients with high risk Ewing's sarcoma.

Adolescent↗
PubMed1997

Donor lymphocyte infusion for childhood acute lymphoblastic leukaemia relapsing after bone marrow transplantation.

Four children with acute lymphoblastic leukaemia (ALL) who relapsed after allogeneic bone marrow transplantation (BMT) were treated with donor lymphocyte infusion (DLI) without prior conditioning. Three patients had previously received a non-T-cell-depleted matched sibling BMT and the fourth had a T-cell-depleted matched unrelated BMT. Two patients developed grade III-IV acute graft-versus-host-disease (GVHD) of the skin, which required intervention. Both are alive in complete haematological remission 7 and 10 months from DLI with chronic GVHD of the skin requiring immunosuppressive therapy. A third patient went into haematological remission 6 weeks after DLI, but with no clinical evidence of GVHD. His bone marrow remained in remission 11 months post-DLI despite the disease (ALL) relapsing in extramedullary sites. The fourth patient showed no clinical or haematological response to three consecutive doses of DLI given at 4-weekly intervals and died from progressive disease 11 months after relapse. These preliminary observations indicate that in constrast to experience in adult ALL, DLI may be effective in inducing sustained remission in children with ALL relapsing after BMT, and a response may occur even in the absence of clinical evidence of GVHD.

Adolescent↗
PubMed1997

An economic evaluation of the use of granulocyte colony-stimulating factor after bone marrow transplantation in children.

Studies that have assessed the use of granulocyte colony-stimulating factor (G-CSF) following bone marrow transplantation have shown a significantly reduced time to neutrophil recovery with the use of this agent, which may translate into a reduced duration of antimicrobial therapy and hospitalisation. We performed a pharmacoeconomic study evaluating the elective use of G-CSF after bone marrow transplantation in children. 22 consecutive children who underwent bone marrow transplantation and received G-CSF 5 micrograms/kg/day were compared with 18 such children (control group) who did not receive G-CSF. Despite a significant reduction in time to recovery of the absolute neutrophil count (ANC) to > 0.5 x 10(9)/L in G-CSF recipients compared with the control group (14 days vs 20.9 days; p < 0.0001), there was only a trend towards a reduction in the duration of intravenous antimicrobial therapy (14.5 days vs 18.6 days; p = 0.15), and there was no significant difference in the duration of hospitalisation (25.3 days vs 29.8 days). Reasons for prolonged hospitalisation beyond ANC recovery included continued use of total parenteral nutrition, treatment of graft-versus-host disease and treatment of ongoing infection. Overall, the mean total cost for patients receiving G-CSF was Pounds 15001, compared with Pounds 15482 for the control group (1995 values). In conclusion, while there appears to be no benefit in financial terms, the release of a child from strict isolation as a result of early ANC recovery must be taken into consideration.

Bone Marrow Transplantation↗
PubMed1997

Quantitative flow cytometry can predict childhood acute lymphoblastic leukaemia presenting with aplasia.

Acute lymphoblastic leukaemia (ALL) presenting as a transient pancytopenia is known to occur in children and less commonly in adults. The period of pancytopenia usually resolves after about 5-38 weeks, to be followed by overt ALL. The pathogenesis is not known and there are no specific cytogenetic abnormalities. Diagnosis is often difficult during the period of bone marrow hypoplasia. Quantitative flow cytometry can help to establish early diagnosis, and can be used on more patients presenting in a similar way.

Adolescent↗