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A Z Rohatiner

Publications and source records attributed to A Z Rohatiner.

At least 19 recordsLinked to original sources
PubMed2001

Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-Hodgkin's lymphoma.

PURPOSE: To assess whether pre-high-dose therapy (HDT)-related factors play a critical role in the development of therapy-related myelodysplasia (tMDS) or secondary acute myelogenous leukemia (sAML). PATIENTS AND METHODS: Twenty-nine of 230 patients with a primary diagnosis of non-Hodgkin's lymphoma (NHL) developed tMDS/sAML after HDT comprising cyclophosphamide and total-body irradiation (TBI) supported by autologous hematopoietic progenitor cells. G-banding and fluorescence in-situ hybridization (FISH) were used to detect clonal cytogenetic abnormalities. RESULTS: The majority of patients showed complex karyotypes at diagnosis of tMDS/sAML containing, in particular, complete or partial loss of chromosomes 5 and/or 7. Using single locus-specific FISH probes, significant levels of clonally abnormal cells were found before HDT in 20 of 20 tMDS/sAML patients screened, compared with three of 24 patients screened who currently have not developed tMDS/sAML, at a median follow-up of 5.9 years after HDT. CONCLUSION: Prior cytotoxic therapy may play an important etiologic role and may predispose to the development of tMDS/sAML. Using a triple FISH assay designed to detect loss of chromosomal material from 5q31, 7q22, or 13q14, significant levels of abnormal cells can be detected before HDT and may predict which patients are at increased risk of developing secondary disease. Further prospective evaluation of this FISH assay is warranted to determine its predictive power in this setting.

Chromosome Aberrations↗
PubMed2001

Lung cancer after Hodgkin's disease: a nested case-control study of the relation to treatment.

PURPOSE: To investigate the causes of the raised risk of lung cancer in patients who have had Hodgkin's disease, and in particular the relationship to treatment. PATIENTS AND METHODS: A nested case-control study was conducted within a cohort of 5,519 patients with Hodgkin's disease treated in Britain during 1963 through 1993. For 88 cases of lung cancer and 176 matched control subjects, information on treatment and other risk factors was extracted from hospital case-notes, and odds ratios for lung cancer in relation to these factors were calculated. RESULTS: Risk of lung cancer was borderline significantly greater in patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy than those who did not receive this treatment (relative risk [RR] = 1.66; 95% confidence interval [CI], 0.99 to 2.82), and increased with number of cycles of MOPP (P =.07). Exclusion of lung cancers for which histologic confirmation was not available strengthened these associations (RR = 2.41; 95% CI, 1.33 to 4.51; P =.004 for any MOPP and P =.007 for trend with number of cycles of MOPP). Risks were not raised, however, after chlorambucil, vinblastine, procarbazine, and prednisone treatment. There was evidence that the raised risk of lung cancer occurring in relation to radiotherapy was restricted to histologies other than adenocarcinoma. CONCLUSION: The results suggest that MOPP chemotherapy may lead to elevated risk of lung cancer, at least in certain subgroups of patients. The role of chemotherapy in the etiology of lung cancer after Hodgkin's disease deserves further investigation.

Adult↗
PubMed2001

Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia.

Between 1972 and 1988, 832 consecutive patients were treated for acute leukaemia at St. Bartholomew's Hospital; a retrospective analysis has been conducted to determine the clinical course and outcome for 101 who have survived > or = 10 years following treatment. At a median follow-up of 16 years (range 10-28 years), 86 patients (86 out of 834 total, 11%) were still alive. Long-term follow-up of patients who have survived > or = 10 years following treatment for acute leukaemia revealed that most patients were in normal health, although a significant number of complications had occurred.

Acute Disease↗
PubMed2001

Loss of CD20 expression following treatment with rituximab (chimaeric monoclonal anti-CD20): a retrospective cohort analysis.

A retrospective analysis of CD20 expression following rituximab for B-cell non-Hodgkin's lymphoma demonstrated a significant change in immunophenotype in 6/25 (24%) patients with persistent bone marrow (BM) infiltration. In three out of six patients, the B cells were uniformly CD20-/CD79alpha+, consistent with frank loss of CD20 expression. In the remaining three cases, the BM infiltrate was predominantly (> 80%) CD20-/CD79alpha+. Two of the former but none of the latter three cases achieved a clinical response. In three further cases, the post-treatment BM infiltrate was composed entirely of benign or reactive CD3+ T cells. Frank loss of CD20 was not seen in 25 post-treatment lymph node biopsies. Immunophenotyping is therefore an important adjunct in the diagnosis of BM infiltration following rituximab.

Antibodies, Monoclonal↗
PubMed2000

Successful therapy of transplant-associated veno-occlusive disease with a combination of tissue plasminogen activator and defibrotide.

A 36-year-old man underwent matched unrelated donor bone marrow transplantation for chronic myeloid leukaemia. He developed severe hepatic veno-occlusive disease as an early post-transplant complication. Tissue plasminogen activator was initially felt to be contraindicated since the patient had concomitant pericarditis. Defibrotide was therefore commenced as treatment for veno-occlusive disease. The pericarditis improved but the veno-occlusive disease continued to worsen (peak bilirubin 353 micromol/l). Tissue plasminogen activator followed by a heparin infusion was therefore administered. However, he proceeded to develop haemorrhagic cardiac tamponade that required drainage. Thrombolysis was therefore discontinued and treatment with defibrotide resumed after an interval of 48 h. The veno-occlusive disease gradually resolved and defibrotide was discontinued once the bilirubin had plateaued. He was discharged home on day +52 post-transplant.

Adult↗
PubMed2000

High-dose treatment with autologous bone marrow support as consolidation of first remission in younger patients with acute myelogenous leukaemia.

BACKGROUND: Debate and controversy remain as to the optimal post-remission therapy for younger patients with acute myelogenous leukaemia (AML). The aim of this study was to evaluate high-dose treatment (HDT) with autologous bone marrow support (ABMS) as consolidation of first complete remission (CR). PATIENTS AND METHODS: One hundred forty-four patients (AML-M3 excluded, median age 38 years, range 15-49 years) received remission induction therapy comprising: adriamycin 25 mg/m2, days 1-3, cytosine arabinoside (ara-C) and 6-thioguanine, both at 100 mg/m2 bid, days 1-7. Patients in whom CR was achieved received two further cycles of the same treatment prior to bone marrow being harvested and cryopreserved. HDT comprised ara-C: 1 g/m2 b.i.d. x six days and total body irradiation (TBI): 200 cGy b.i.d. for three days. Thawed autologous marrow was then re-infused. RESULTS: Complete remission was achieved in 106 of 144 patients (73%) who were thus eligible to receive ara-C + TBI + ABMS; 61 actually received it. Following HDT, the median time to neutrophil recovery (> 0.5 x 10(9)/l) was 25 days (range 11-72 days) and to platelet recovery (> 20 x 10(9)/l), 42 days (range 15-159 days). There were eight treatment-related deaths. Analysis by 'intention to treat' shows both remission duration (log-rank, P = 0.001) and survival (log-rank, P = 0.004) to be significantly longer for the 106 patients eligible to receive HDT than for a historical control group (n = 133) who received identical remission induction and consolidation therapy but without ara-C + TBI + ABMS. With a median follow-up of 5.5 years, 39 of 106 patients remain in CR (37%) and 54 (51% of those in whom CR was achieved) remain alive, with a predicted actuarial survival of 52% at 5 years. CONCLUSIONS: The addition of ara-C + TBI + ABMS to conventional consolidation therapy significantly improved remission duration and survival over those of a historical control group of patients with AML (aged < 50, AML-M3 excluded). HDT was, however, associated with significant treatment-related mortality and slow blood count recovery. The use of ara-C + TBI supported by peripheral blood progenitor cells should make the treatment safer and more widely applicable in AML.

Adolescent↗
PubMed2000

Low-dose continuous chemotherapy (LBCMVD-56) for refractory and relapsing lymphoma.

BACKGROUND: Although lymphoid malignancies are generally chemosensitive, relapse is common. The use of high-dose therapy can make subsequent cytotoxic therapy intolerable. There is a need to develop regimens with low acute toxicity which are suitable for use in patients post-high dose therapy and following the failure of standard protocols. PATIENTS AND METHODS: Twenty-six patients with lymphomas, fifteen of whom had received high-dose therapy, were treated with a novel regimen consisting of low-dose lomustine, chlorambucil, daily subcutaneous bleomycin, vincristine and methotrexate with dexamethasone on an eight-week cycle (LBCMVD-56). A median of three cycles was given. RESULTS: The overall response rate at 12 weeks was 67% (21% complete remission (CR)) with a median overall survival of 13 months. A symptomatic response was seen in 72%. Previous high-dose therapy did not compromise the response rate. Toxicity was acceptable with grade 3-4 haematological toxicity seen in 27% of cycles, gastrointestinal toxicity seen in 11% and pulmonary toxicity seen in 8%. Thirty-one percent of patients required hospitalisation at some point during this treatment most commonly for neutropenic sepsis. CONCLUSIONS: LBCMVD-56 is an inexpensive, outpatient-based regimen with low acute toxicity and a high response rate in this heavily pre-treated group of patients.

Adolescent↗
PubMed2000

Patterns of relapse and subsequent management following high-dose chemotherapy with autologous haematopoietic support in relapsed or refractory Hodgkin's lymphoma: a two centre study.

BACKGROUND: High-dose chemotherapy has an established role in recurrent or refractory Hodgkin's lymphoma (HL) although a significant proportion of patients subsequently relapse. This manuscript describes the clinical characteristics of such patients and documents their further management at two major UK cancer centres. PATIENTS AND METHODS: Between 1987 and 1996 one hundred patients with recurrent or refractory HL received high-dose chemotherapy (HDCT) with autologous haematopoietic rescue. All had recurred within 12 months of initial therapy or had two or more recurrences. RESULTS: With a median follow-up of 2 years, 56 patients are currently progression-free. There were six treatment-related deaths. One patient died of pneumonia in remission. Thirty-seven patients have relapsed, intrapulmonary disease being seen for the first time in 53% and recurrence at previous sites of disease in 81%. Following recurrence, therapy was determined by circumstances: either one agent at a time was used (single sequential approach) or multiagent chemotherapy was chosen. There was a survival advantage for those who achieved a symptomatic response (13 vs. 4 months median, P = 0.0001). A trend towards longer survival was seen for those whose disease recurred beyond six months following high-dose chemotherapy and in those who received combination chemotherapy. CONCLUSIONS: These results confirm that HDCT with autologous haematopoietic support is inadequate for about half the patients who receive it for high-risk HL. Relapse in the site of prior disease is the most likely pattern with intrapulmonary disease for the first time occurring frequently. It is possible to administer further chemotherapy after failure of HDCT, and both objective as well as subjective benefit can be achieved. A few patients appear to get long-term benefit from further treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

A phase II study to evaluate the combination of fludarabine, mitoxantrone and dexamethasone (FMD) in patients with follicular lymphoma.

BACKGROUND: 'Molecular response' is being investigated as a therapeutic goal in follicular lymphoma (FL). High response rates in FL with the fludarabine combination 'FMD' have been associated with 'molecular remission'. A phase II study of FMD in FL was therefore conducted. PATIENTS AND METHODS: Fifty-four patients, ten of whom were newly diagnosed received FMD. Forty-four percent of the previously treated patients had 'chemoresistant' disease. Treatment comprised: fludarabine 25 mg/m2 days 1-3, mitoxantrone 10 mg/m2 day 1, and dexamethasone 20 mg days 1-5. Blood/bone marrow was collected for quantitation of t(14;18) by 'real-time' PCR. RESULTS: The overall response rate was 37 of 54 (69%), complete responses being seen in 11 patients (20%), with no difference between newly diagnosed and the previously treated patients. However, the response rate in 'chemosensitive' relapse was 84% compared to 44% in patients in whom the last prior regimen had failed. Molecular responses were seen in 17 of 25 and PCR negativity in 8 of 25, although molecular and clinical responses did not always correlate. Toxicity was moderate, 19 patients required admission. However, in 6 of 12 patients, subsequent G-CSF mobilised stem cell harvests failed. CONCLUSIONS: FMD was well tolerated but with a lower than expected response rate. Molecular responses were seen in the majority of responding patients however, 'molecular remission' was rare.

Adult↗
PubMed2000

Role of early anthracycline dose-intensity according to expression of Philadelphia chromosome/BCR-ABL rearrangements in B-precursor adult acute lymphoblastic leukemia.

INTRODUCTION: The use of anthracycline antibiotics in adult acute lymphoblastic leukemia (ALL) has resulted in an improved outcome to remission induction therapy. However,the exact role of these drugs in consolidation therapy is less clear, especially in specific ALL subsets. MATERIALS AND METHODS: A retrospective analysis was conducted on the outcome of 308 patients (median age 35 years, range 13-75) with the most frequent subtype, early-B ALL, treated between 1974 and 1998 on eight consecutive protocols. Anthracycline-related effects were assessed by evaluating the impact of planned anthracycline dose-intensity (A-DI) on long-term outcome. A-DI (in mg/m(2)/week) during the first twelve weeks of consolidation therapy was classified as either "high" (doxorubicin>20, idarubicin>7) or "low". RESULTS: Complete remission was achieved in 78% of cases. With a median follow-up of 6.5 years, on multivariate analysis, disease-free survival (DFS) correlated only with expression of the Philadelphia (Ph) chromosome and/or associated BCR-ABL rearrangements (Ph/BCR(+)) (P=0.0001) and planned A-DI (P<0.0001). On this basis, four major prognostic groups with significantly different DFS could be identified: (1) Ph/BCR(-), "high" A-DI (n=102), median 3.5 years and 41% at five years, respectively; (2) Ph/BCR(-), "low" A-DI (n=64), 1.3 years and 16%; (3) Ph/BCR(+), "high" A-DI (n=35), 1.7 years and 20%; (4) Ph/BCR(+), "low" A-DI (n=39), 0.75 years and 0%. When analyzed separately for Ph/BCR(-) (n=166) and Ph/BCR(+) (n=74) patients, the A-DI effect on DFS was preserved in the former (P=0.018) whereas, in Ph/BCR(+) patients, only age <50 years (P=0.004) and blast count <25 x 10(9)/l (P=0.02) correlated with better DFS. However, Ph/BCR(+) patients with the best prognostic profile (age <50 years and blast count <25 x 10(9)/l; n=21) who were treated on "high" A-DI regimens experienced a median DFS of 2.2 years with DFS 21% at five years, compared to 0.67-1 years and 0-10% in other cases (n=53, P<0.01). CONCLUSION: A "high" A-DI may act as a positive treatment-related prognostic factor in early B-lineage ALL. Although mainly restricted to patients with Ph/BCR(-) ALL, A-DI could also influence the outcome in Ph/BCR(+) patients with other favorable prognostic factors.

Adolescent↗
PubMed2000

Factors which predict unsuccessful mobilisation of peripheral blood progenitor cells following G-CSF alone in patients with non-Hodgkin's lymphoma.

INTRODUCTION: High-dose therapy with haematopoietic progenitor cell support has increasingly been utilised for patients with haematological malignancies. Peripheral blood is the stem cell source of choice, however, various mobilisation strategies are used by different centres. PATIENTS AND METHODS: Over a 2-year period, 52 patients with non-Hodgkin's lymphoma (median age 47 years, range 16-64 years) underwent peripheral blood progenitor cell mobilisation using G-CSF alone (16 microg/kg/day). The harvest was considered successful if > or =1 x 10(6) CD34(+) cells/kg were collected by leukapheresis. The histological subtypes of non-Hodgkin's lymphoma comprised: follicular (24 patients), diffuse large B-cell (14 patients), lymphoplasmacytoid (four patients), mantle cell (three patients), lymphoblastic lymphoma (one patient) and small lymphocytic lymphoma/chronic lymphocytic leukaemia (six patients). The median interval from diagnosis of non-Hodgkin's lymphoma to mobilisation was 27 months (range 2 months to 17 years). The median number of prior treatment episodes was 2 (range 1-5); 26 patients had received fludarabine alone or in combination. At the time of peripheral blood progenitor cell mobilisation, 20 patients were in 1st remission and 32 were in > or =2nd remission; 30 patients were in partial remission and 22 were in complete remission; the bone marrow was involved in nine patients. RESULTS: Peripheral blood progenitor cell mobilisation/harvest was unsuccessful in 19 out of 52 (37%) patients (mobilisation: 18, harvest: 1). The factors associated with unsuccessful mobilisation or harvest were: prior fludarabine therapy (P=0.002), bone marrow involvement at diagnosis (P=0.002), bone marrow involvement anytime prior to mobilisation (P=0.02), histological diagnosis of follicular, mantle cell, or lymphoplasmacytoid lymphoma, or small lymphocytic lymphoma/chronic lymphocytic leukaemia (P=0.03) and female gender (P=0.04). CONCLUSION: Although peripheral blood progenitor cells can be successfully mobilised and harvested from the majority of patients with non-Hodgkin's lymphoma after treatment with G-CSF alone, the latter is unsuccessful in approximately one-third of patients. These factors should be taken into account when patients are being considered for high-dose treatment.

Adolescent↗
PubMed2000

A UK multicentre phase II study of rituximab (chimaeric anti-CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response.

Follicular lymphoma (FL) cells express CD20 and are associated in most cases with the t(14;18) chromosomal translocation. A multicentre study was undertaken between January 1997 and January 1998 to assess the complete response rate (CR) and overall response rate (RR) to rituximab, a chimaeric anti-CD20 monoclonal antibody. Seventy patients with previously treated FL received rituximab (375 mg/m2/week x4, by intravenous infusion). Restaging studies were performed 1 and 2 months after therapy. Molecular monitoring for the presence of cells harbouring the Bcl-2/JH gene rearrangement in the peripheral blood (PB) and bone marrow (BM) was performed before and after treatment using a two-step semi-nested polymerase chain reaction (PCR) assay. The overall RR was 32/70 (46%), being highest in patients who had received only one previous treatment (12/15, 80%). However, only two patients achieved a CR. The median duration of response was 11 months. Thirteen of 21 evaluable 'PCR-positive' patients (62%) became 'PCR-negative' in PB and/or BM samples 1 month after rituximab, although this did not correlate with clinical response. Treatment was generally well tolerated, although one patient developed Stevens-Johnson syndrome. Rituximab was shown to be active in FL, and in some cases PB and/or BM became PCR negative. Studies in combination with cytotoxic chemotherapy to increase the CR rate are warranted.

Adult↗
PubMed2000

European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma.

PURPOSE: Mantle-cell lymphoma (MCL), immunocytoma (IMC), and small B-cell lymphocytic lymphoma (SLL) are B-cell malignancies that express CD20 and are incurable with standard therapy. A multicenter phase II study was conducted to assess the toxicity and the overall response rates (RR) and complete response (CR) rates to rituximab (chimeric anti-CD20 monoclonal antibody). PATIENTS AND METHODS: Between January 1997 and January 1998, 131 patients with newly diagnosed MCL (MCL1; n = 34) and previously treated MCL (MCL2; n = 40), IMC (n = 28), and SLL (n = 29) received rituximab 375 mg/m(2)/wk for 4 weeks via intravenous infusion. Restaging studies were performed 1 and 2 months after treatment. An analysis of the duration of response was conducted in December 1998. RESULTS: Eleven patients were unassessable, including one who died of splenic rupture after the first infusion. The RR among the 120 assessable patients was 30% (36 of 120 patients). The RR by histology was as follows: MCL1, 38%; MCL2, 37%; IMC, 28%; and SLL, 14%. Ten patients, all with MCL, achieved CR. The median duration of response in MCL was 1.2 years. Immediate side effects were common and usually responded to adjustments in the infusion rate. There were 31 episodes of infection after treatment; most cases were mild. Cardiac arrhythmia and ophthalmologic side effects occurred in 10 and nine patients, respectively, including one case of severe loss of visual acuity. CONCLUSION: Single-agent rituximab has moderate activity in MCL and IMC but only limited activity in SLL. The duration of response in MCL was similar to that previously reported in follicular lymphoma. Its use in combination with cytotoxic chemotherapy to increase the CR rate is warranted in MCL and IMC.

Adult↗
PubMed2000

High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up.

PURPOSE: To evaluate the long-term results of high-dose therapy (HDT) in follicular lymphoma, with specific emphasis on the prognostic significance of polymerase chain reaction (PCR)-detectable Bcl-2/IgH rearrangements. PATIENTS AND METHODS: Between June 1985 and October 1995, 99 patients with follicular lymphoma received HDT as consolidation of second or subsequent remission. Bone marrow was treated in vitro with anti-B-cell antibodies and complement. RESULTS: Sixty-five patients remained alive, 49 treatment-failure free, with a median follow-up of 5.5 years (range, 1.5 to 12.5 years). Four "early" and 10 "late" deaths occurred from treatment-related causes; seven of the latter were due to secondary myelodysplasia (s-MDS) or secondary acute myeloblastic leukemia. Overall, 12 (12%) of the 99 patients developed s-MDS or acute myeloblastic leukemia. Kaplan-Meier estimates of freedom from recurrence (FFR) and survival rates at 5 years were 63% (95% confidence interval [CI], 52% to 72%) and 69% (95% CI, 58% to 78%), respectively. For all 99 patients, in multivariate analysis, absence of the Bcl-2/IgH rearrangement at the time of diagnosis (hazards ratio [HR], 0.39; P =.04) and three or fewer treatment episodes before HDT (HR, 0.03; P =.001) were significant prognostic factors for improved survival. For patients bearing Bcl-2/IgH rearrangements, in univariate and multivariate analyses, absence of a PCR-detectable Bcl-2/IgH rearrangement during follow-up was associated with a significantly lower risk of recurrence (adjusted HR, 0.13; P <.001) and death (HR, 0.25; P =.02), whereas the PCR status of the reinfused bone marrow did not correlate with outcome. CONCLUSION: Prolonged FFR can be achieved in patients with follicular lymphoma after HDT, but as yet there is no survival advantage compared with conventional treatment. These results confirm that elimination of cells bearing the Bcl-2/IgH rearrangement is highly desirable and should be attempted. The incidence of s-MDS is of increasing concern in this setting.

Adult↗
PubMed2000

Therapy-related myelodysplasia and secondary acute myelogenous leukemia after high-dose therapy with autologous hematopoietic progenitor-cell support for lymphoid malignancies.

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q-, 15 had -7/7q-, seven had -18/18q-, seven had -13/13q-, and four had -20/20q-. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P =.009) and older age (P =.02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P =.05 and.07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.

Adolescent↗
PubMed2000

Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas.

PURPOSE: This multicenter phase II study evaluated the efficacy, dosimetry methodology, and safety of iodine-131 tositumomab in patients with chemotherapy-relapsed/refractory low-grade or transformed low-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients received a dosimetric dose that consisted of 450 mg of anti-B1 antibody followed by 35 mg (5 mCi) of iodine-131 tositumomab. Serial total-body gamma counts were then obtained to calculate the patient-specific millicurie activity required to deliver the therapeutic dose. A therapeutic dose of 75 cGy total-body dose (attenuated to 65 cGy in patients with platelet counts of 101,000 to 149,000 cells/mm(3)) was given 7 to 14 days after the dosimetric dose. RESULTS: Forty-five of 47 patients were treated with a single dosimetric and therapeutic dose. Twenty-seven patients (57%) had a response. The response rate was similar in patients with low-grade (57%) or transformed low-grade (60%) NHL. The median duration of response was 9.9 months. Fifteen patients (32%) achieved a complete response (CR; 10 CRs and five clinical CRs), including five patients (50%) with transformed low-grade NHL. The median duration of CR was 19.9 months, and six patients have an ongoing CR. Treatment was well tolerated, with the principal toxicity being hematologic. The most common nonhematologic toxicities that were considered to be possibly related to the treatment included mild to moderate fatigue (32%), nausea (30%), fever (26%), vomiting (15%), infection (13%), pruritus (13%), and rash (13%). Additionally, one patient developed human-antimouse antibodies. CONCLUSION: Iodine-131 tositumomab produced a high overall response rate, and approximately one third of patients had a CR despite having chemotherapy-relapsed or refractory low-grade or transformed low-grade NHL.

Adult↗