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John P Leonard

Publications and source records attributed to John P Leonard.

At least 19 recordsLinked to original sources
PubMed2026

Venetoclax added to dose-adjusted EPOCH-R for newly diagnosed double-hit lymphomas: phase 2 results from ALLIANCE A051701, an open-label, randomised, controlled, phase 2-3 trial.

BACKGROUND: High-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6, known as double-hit lymphoma, is a highly aggressive malignancy with poor outcomes after standard chemoimmunotherapy. We aimed to study whether the addition of the BCL2-inhibitor venetoclax to chemoimmunotherapy in patients with double-hit lymphoma resulted in superior efficacy compared with chemotherapy alone. METHODS: ALLIANCE A051701 is an open-label, randomised, controlled, phase 2-3 trial in separate cohorts of patients with double-hit lymphoma and patients with double-expressor lymphoma. In this analysis, we report phase 2 results from the double-hit lymphoma cohort. Patients aged 18-80 years with newly diagnosed double-hit lymphoma and Eastern Cooperative Oncology Group (ECOG) performance status 0-2 were recruited from 41 hospitals and outpatient clinics in the USA. Patients were randomly assigned (1:1) to receive DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) either alone (DA-EPOCH-R group) or with venetoclax (DA-EPOCH-R plus venetoclax group) using permuted block randomisation schedule. All patients and investigators were aware of group assignment. DA-EPOCH-R was administered on a 21-day schedule for up to six total cycles. Venetoclax was given as 600 mg by mouth daily on days 4-8 of cycle 1 and on days 1-5 of cycles 2-6. The primary endpoint was progression-free survival in the modified intent-to-treat population inclusive of all eligible patients with centrally confirmed double-hit lymphoma. The safety analysis population consisted of all evaluable patients who received at least one dose of protocol treatment. This trial is registered with ClinicalTrials.gov (NCT03984448) and is closed to enrolment. FINDINGS: 36 patients were randomly assigned to the DA-EPOCH-R group and 37 to the DA-EPOCH-R plus venetoclax group between Oct 22, 2019, and Sept 18, 2020. Median age was 65 years (IQR 56-73) and baseline demographic factors were well balanced between groups, with 30 (45%) female and 36 (55%) male patients. Most patients (59 [89%]) were white, two (3%) were Asian, one (2%) was Black or African American, and four (6%) had unknown or unreported ethnicity. The majority of patients had MYC-BCL2 double-hit lymphoma (59 [89%] patients), advanced stage disease (57 [86%] patients), and high-intermediate/high-risk IPI score (42 [64%] patients). Median follow-up was 34·7 months (IQR 30·1-36·8). Median progression-free survival was 28·4 months (95% CI 5·2-not estimable) in the DA-EPOCH-R group (n=30) and 7·7 months (95% CI 4·7-NE) in the DA-EPOCH-R plus venetoclax group (n=36; hazard ratio [HR] 1·13, 95% CI 0·53-2·37; p=0·75). Deaths on treatment occurred in one (3%) patient in the DA-EPOCH-R group (due to dyspnoea; possibly related to treatment) and six (17%) patients in the DA-EPOCH-R plus venetoclax group (four due to sepsis [three at least possible related and one unrelated], two due to cardiac arrest [at least possibly related]), prompting early closure of the double-hit lymphoma cohort. The most common grade 3-4 non-haematological adverse event was febrile neutropenia, occurring in 15 (43%) of 35 patients in the DA-EPOCH-R plus venetoclax group and 11 (37%) of 30 patients in the DA-EPOCH-R group. The median overall survival has not been reached in either group. The 24-month overall survival estimates were 72% (95% CI 52-85) in the DA-EPOCH-R group compared with 52% (95% CI 33-68) in the DA-EPOCH-R plus venetoclax group (HR 2·49, 95% CI 1·03-6·04; p=0·038). INTERPRETATION: The addition of venetoclax to DA-EPOCH-R resulted in excess mortality, prompting early study closure. Robust accrual shows that prospective multicentre trials are feasible in double-hit lymphoma, and the outcomes in the DA-EPOCH-R group serve as a benchmark for future studies. FUNDING: National Cancer Institute of the National Institutes of Health.

Humans↗
PubMed2022

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee.

Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.

Advisory Committees↗
PubMed2006

FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease.

BACKGROUND: Early prediction of response to therapy may offer the potential to identify patients who will benefit from standard conventional therapy. The objective of this study was to determine the predictive value of FDG-PET as an early response indicator after 1 cycle of chemotherapy for progression-free survival (PFS) in diffuse large cell lymphoma (DLCL) and classic Hodgkin disease (HD). METHODS: FDG-PET was performed before, after 1 cycle, and after completion of chemotherapy in 47 patients. The patients were followed with a median follow-up of 21 months (range, 3-47 months). PFS was compared between PET-positive and PET-negative patients after 1 cycle and after completion of therapy. RESULTS: All PET-negative patients after 1 cycle (n = 31) had sustained complete remission with a median follow-up of 28 months. Fourteen of 16 PET-positive patients after 1 cycle had refractory disease or relapsed (median PFS, 5.5 months). There were 2 false-positive results, 1 with an active infection at the biopsy site and the other in a patient who had been in remission after radiation therapy. There was good agreement between the results obtained after 1 cycle and at completion of therapy (kappa, 0.80); however, the negative predictive value was higher for FDG-PET after 1 cycle than after completion of chemotherapy (100% vs 91.4%), although not statistically different (P = .40). CONCLUSIONS: FDG-PET had a high prognostic value after 1 cycle of chemotherapy, thus it can be a valid alternative for posttreatment evaluation of DLCL and HD and may offer the potential for change in treatment paradigms.

Adolescent↗
PubMed2006

A phase 2 study of rituximab in combination with recombinant interleukin-2 for rituximab-refractory indolent non-Hodgkin's lymphoma.

PURPOSE: The incidence of non-Hodgkin's lymphoma (NHL), the fifth most common malignancy in the United States, has increased over 70% in the last 30 years. Fifty percent to 75% of patients with low-grade or follicular NHL respond to rituximab therapy. However, responses are generally of limited duration, and complete responses are rare. Preclinical work suggests that human recombinant interleukin-2 (rIL-2; aldesleukin, Proleukin) enhances rituximab efficacy. Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action of rituximab. rIL-2 induces expansion and activation of Fc receptor (FcR)-bearing cells, thereby enhancing ADCC. Therefore, a large, multicenter phase 2 trial to assess the effects of rIL-2 on rituximab therapy in patients with rituxumab-refractory low-grade NHL was conducted. EXPERIMENTAL DESIGN: The combination of rituximab and rIL-2 was studied in 57 patients with rituximab-refractory low-grade NHL (i.e., patients must have received a single-agent course of rituximab and showed no tumor response, or had a response lasting <6 months). I.V. rituximab was given at 375 mg/m(2) (weeks 1-4). S.C. rIL-2 was given thrice a week at 14 MIU (weeks 2-5) and at 10 MIU (weeks 6-9). RESULTS: Rituximab plus rIL-2 combination therapy was safe and generally well tolerated, but responses were low. Fifty-seven patients were enrolled with 54 evaluable for response; however, only five responses (one complete and four partial) were observed. Correlative data indicate that rIL-2 expanded FcR-bearing cells and enhanced ADCC. However, other factors, such as FcgammaR polymorphisms in patients refractory to single-agent rituxumab and heterogeneous tumor biology, may have influenced the lack of clinical efficacy seen with this combination therapy. CONCLUSIONS: rIL-2 expands FcR-bearing cellular subsets in vivo and enhances in vitro ADCC of rituxumab. However, these findings do not directly translate into meaningful clinical benefit for patients with rituxumab-refractory NHL.

Adult↗
PubMed2006

Magnitude of stromal hemangiogenesis correlates with histologic subtype of non-Hodgkin's lymphoma.

PURPOSE: Tumor stromal microenvironment promotes neoplastic growth and angiogenesis. We have previously shown that recruitment of marrow-derived vascular endothelial growth factor receptor-1(+) (VEGFR-1(+)) proangiogenic hematopoietic progenitors contributes instructively and structurally to neoangiogenesis in mouse models. Here, we investigated whether stromal incorporation of CD68(+) hemangiogenic cells and alpha-smooth muscle actin(+) (alpha-SMA(+)) stromal cells correlates with neoangiogenesis and progression in human non-Hodgkin's lymphoma subtypes. EXPERIMENTAL DESIGN: Spatial localizations of vascular and stromal cells expressing CD34, VEGFR-1, alpha-SMA, and CD68 were examined by immunohistochemistry in 42 cases of non-Hodgkin's lymphoma, including diffuse large B-cell lymphoma, Burkitt lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and compared with benign follicular hyperplasia. RESULTS: Compared with indolent lymphomas, there was a profound increase in recruitment of CD68(+) cells and VEGFR-1(+) neovessels in aggressive subtypes (including those transformed from indolent subtypes), where CD68(+) cells were localized to the perivascular region of neovessels as well as the stromal compartment. The perivascular CD68(+) cells expressed VEGFR-1 and VEGF-A. In contrast, there was a diffuse increase in alpha-SMA incorporation throughout the stromal compartment of indolent subtype of CLL/SLL compared with the scant perivascular pattern in aggressive subtypes. Overall, there was no correlation between CD34(+) microvessel density and lymphoma histologic subtype. CONCLUSIONS: Heightened stromal hemangiogenesis as marked by infiltration of proangiogenic VEGFR-1(+)CD68(+)VEGF-A(+) cells and their paracrine cross-talk with neovasculature appears to be a distinct feature of aggressive lymphoma, providing novel targets for antiangiogenic therapy, whereas alpha-SMA(+) stromal vascular network may be differentially targeted in CLL/SLL.

Actins↗
PubMed2006

Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma.

PURPOSE: Evaluate response rate, duration of response (DOR), time-to-progression (TTP), overall survival (OS), and safety of bortezomib treatment in patients with relapsed or refractory mantle cell lymphoma (MCL). PATIENTS AND METHODS: Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 of a 21-day cycle, for up to 17 cycles. Response and progression were determined using International Workshop Response Criteria, both using data from independent radiology review and by the investigators. Primary efficacy analyses were based on data from independent radiology review. RESULTS: In total, 155 patients were treated. Median number of prior therapies was one (range, one to three). Response rate in 141 assessable patients was 33% including 8% complete response (CR)/unconfirmed CR. Median DOR was 9.2 months. Median TTP was 6.2 months. Results by investigator assessments were similar. Median OS has not been reached after a median follow-up of 13.4 months. The safety profile of bortezomib was similar to previous experience in relapsed multiple myeloma. The most common adverse events grade 3 or higher were peripheral neuropathy (13%), fatigue (12%), and thrombocytopenia (11%). Death from causes that were considered to be treatment related was reported for 3% of patients. CONCLUSION: These results confirm the activity of bortezomib in relapsed or refractory MCL, with predictable and manageable toxicities. Bortezomib provides significant clinical activity in terms of durable and complete responses, and may therefore represent a new treatment option for this population with usually very poor outcome. Studies of bortezomib-based combinations in MCL are ongoing.

Adult↗
PubMed2006

Proteasome inhibition with bortezomib: a new therapeutic strategy for non-Hodgkin's lymphoma.

The incidence of non-Hodgkin's lymphoma (NHL) has markedly increased in the US and other westernized countries in recent years and presents a considerable clinical challenge. NHL is divided into subtypes that follow an aggressive or indolent course. Follicular lymphoma (FL), the most common indolent subtype, and mantle cell lymphoma (MCL), an aggressive subtype that accounts for approximately 5% of cases, are generally incurable. MCL has a relatively poor prognosis, with a median survival of 3-4 years. Despite improving response rates with new agents and regimens, the lack of demonstrated improvement in overall survival in many subtypes supports the development of novel approaches, such as proteasome inhibition. Bortezomib is the first proteasome inhibitor to be evaluated in human studies. It has already been approved as second-line treatment in multiple myeloma and is now under active investigation in NHL. The US FDA has granted bortezomib fast-track designation for relapsed and refractory MCL. In vitro and in vivo studies have demonstrated single-agent activity against various lymphoid tumors, and additive or synergistic effects in combination with other agents, including standard chemotherapy drugs employed in NHL. Phase 2 clinical trials indicate that bortezomib is well tolerated and active in several NHL subtypes, with response rates of 18-60% in FL and 39-56% in MCL. A number of combination trials are currently underway with a range of standard agents. Bortezomib has the potential to play a significant role throughout the NHL treatment algorithm in the future.

Animals↗
PubMed2006

Phase II trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin's lymphoma resulting in durable clinical responses.

PURPOSE: To evaluate idiotype (Id) vaccination as a single agent in previously treated patients with indolent non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients underwent biopsy for determination of their lymphoma-specific Id sequence. Recombinant Id protein was manufactured and covalently linked with keyhole limpet hemocyanin (KLH) to generate Id/KLH. Patients received Id/KLH 1 mg on day 1 subcutaneously, with granulocyte-macrophage colony-stimulating factor 250 mug on days 1 to 4, monthly for 6 months. Booster injections were administered until progression. Both clinical and immune responses were evaluated. RESULTS: Thirty-two previously treated patients received at least one injection of Id/KLH, and 31 were assessed for efficacy. Responses were observed in four patients (one complete response and three partial responses). Median time to onset of response was 5.9 months (range, 2.3 to 14.1 months). Median duration of response has not been reached but should be at least 19.4 months (range, 10.4 to 27.2+ months). Median time to progression is 13.5 months. The most common adverse events were mild to moderate injection site reactions. Six (67%) of nine patients tested demonstrated a cellular immune response, and four (20%) of 20 patients demonstrated an antibody response against their Id. CONCLUSION: This trial demonstrates that Id/KLH alone can induce tumor regression and durable objective responses. Further study of Id/KLH is recommended in other settings where efficacy may be further enhanced as in first-line therapy or after cytoreductive therapy.

Adult↗
PubMed2006

Subsequent therapy can be administered after tositumomab and iodine I-131 tositumomab for non-Hodgkin lymphoma.

BACKGROUND: Iodine I-131 tositumomab is a well tolerated and effective therapy for recurrent low-grade and transformed low-grade non-Hodgkin lymphoma (NHL). Hematologic reserve after radioimmunotherapy (RIT) is an important consideration when subsequent therapy is required. METHODS: One hundred fifty-five patients who received treatment with I-131 tositumomab were assessed, and 68 patients had progressive disease after RIT. The median age (n=68 patients) was 59 years (range,18-82 yrs), and patients received a median of 2 pre-RIT regimens (range,1-8 regimens), including 66% who received anthracycline, 19% who received platinum, and 50% who received fludarabine. RESULTS: The median time to disease progression (among progressors) was 168 days (range, 19-771 days). At the time they developed recurrent disease, patients had median white blood cell count (WBC) of 4.9 K cells/microL (range, 1.1-21.4 K cells/microL), a median absolute neutrophil count (ANC) of 3.25 K cells/microL (range, 0.59-8.20 K cells/microL), a median platelet count of 130 K cells/microL (range, 9-440 K cells/microL), and there was no significant difference between pre-RIT and recurrence values except for the platelet count (P<0.05). No patient demonstrated a WBC<1.0 K cells/microL or an ANC<0.5 K cells/microL, although 1 patient had a platelet count<10 K cells/microL. Twenty-four patients subsequently received no further chemotherapy; and, in 21 patients (88%), hematologic parameters appeared to allow subsequent chemotherapy if necessary (blood counts: National Cancer Institute Grade 0-2). Among 44 patients (65%) who received further chemotherapy (median, 2 regimens; range, 1-4 regimens), 19 patients (43%) were treated with anthracyclines, 17 patients (39%) were treated with platinum, 10 patients (23%) were treated with fludarabine, and 13 patients (30%) underwent stem cell transplantation. Disease improvement occurred in most patients, although 18 patients died (40%) after further chemotherapy, predominantly from refractory lymphoma. CONCLUSIONS: Most patients with progressive disease after treatment with iodine I-131 tositumomab were able to receive subsequent therapy, including cytotoxic chemotherapy and stem cell transplantation.

Adolescent↗
PubMed2006

A study of a reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation for patients with hematologic malignancies using Campath-1H as part of a graft-versus-host disease strategy.

Nonmyeloablative transplantation (NMT) is intended to be less toxic than traditional allografts, but such regimens as fludarabine/melphalan still pose a significant risk of graft-versus-host disease (GVHD). We used Campath-1H in an attempt to reduce the risk of GVHD in NMT. Patients with hematologic malignancies suitable for allogeneic transplantation underwent transplantation using a regimen of fludarabine 30 mg/m(2) on days -5 to -2 (total, 120 mg/m(2)), total body irradiation of 200 cGy on day -1, and Campath-1H 20 mg/day on days -7 to -3 (total dose, 100 mg). After loss of graft in 5 of the first 6 patients, the protocol was amended by decreasing the Campath-1H dose to 20 mg on days -4 and -3 and 10 mg on day -2 (total dose, 50 mg) for all subsequent patients. GVHD prophylaxis consisted of only cyclosporine, due to the immunosuppressive effect of Campath-1H. Patients received prophylactic acyclovir, fluconazole, and a quinolone. Other requirements included creatinine clearance > or = 25 mL/min, diffusing capacity > or = 45% of predicted, and cardiac ejection fraction > or = 40%. Twenty-five patients with hematologic malignancies entered the study. The median age was 40 years (range, 26-71 years). Median time to engraftment (defined as a neutrophil count of 500 mm(3) and a platelet count of 20,000 mm(3) without platelet support on at least 2 days) was 19 days (range, 9-32 days). All patients who were treated after the amendment engrafted with 90%-100% donor cells by day 100 except for 2 early deaths. Acute GVHD developed in 40% of the patients. Patients who underwent related transplants developed GVHD after donor lymphocyte infusions for poor engraftment or relapse whereas those undergoing unrelated transplants developed GVHD de novo. Two patients (8%) developed chronic GVHD, and 48% had cytomegalovirus reactivation, which was easily managed medically. Nonrelapse mortality within the first 12 months was 12%; 32% of the patients survived at a median of 269 days. We conclude that Campath-1H, fludarabine, and melphalan is a reasonable preparative regimen for reduced-intensity transplantation with a low nonrelapse mortality, but that issues of GVHD remain problematic, due to either the use of donor lymphocyte infusions or the use of volunteer unrelated donors.

Adult↗
PubMed2006

Lymphoma in elderly patients: novel functional assessment techniques provide better discrimination among patients than traditional performance status measures.

BACKGROUND: Age > 60 years and impaired performance status (PS) are adverse prognostic features in the International Prognostic Index for non-Hodgkin's lymphoma; however, patients aged > 60 years compose a heterogeneous population, and commonly used PS measures are subjective and incomplete. PATIENTS AND METHODS: Validated tests are used in geriatric populations to predict mortality and functional decline. The timed "up and go" test measures the time required to stand, walk a set distance, and return. The Tinetti Gait and Balance test measures gait and balance, and the hand grip assesses grip strength. We evaluated these tests in a heterogeneous cohort of older patients with lymphoma, as a first step in identifying prognostic subsets that might differ in the ability to tolerate disease and treatment. The mean age of the patients (N = 25) was 70 years, with 13 men and 12 women. Five patients were newly diagnosed, 15 had aggressive histology, and 10 had indolent disease. Two subjects had Eastern Cooperative Oncology Group PS 0, 20 had PS 1, and 3 had PS 2. Assessments could be conducted in < 5 minutes. Within the largest group (PS 1; n = 20), these tests demonstrated a range of functional status measures. RESULTS: The interquartile range/median (higher values reflect greater variance) was 73.1 for the handgrip, 42.3 for the "up and go," and 1.8 for the Tinetti test. CONCLUSION: Accepted geriatric assessment tools can identify subgroups of older patients with lymphoma with distinct functional status. Prospective trials in larger and more homogeneous patient populations will define the potential of these tools to assist in guiding therapy and predicting outcomes.

Aged↗
PubMed2006

Should all patients with indolent lymphoma be treated with rituximab maintenance therapy? An overview of the data.

Indolent non-Hodgkin's lymphoma remains a generally incurable malignancy. Administration of the anti-CD20 monoclonal antibody rituximab as a single agent or in combination with chemotherapy has become widely employed in this patient population. Although the addition of maintenance treatment after 1 course of single-agent rituximab prolongs time to progression in patients with indolent non-Hodgkin's lymphoma, a similar "duration of rituximab benefit" is observed when rituximab is administered at the time of relapse. Progression-free survival is clearly improved when rituximab is administered with chemotherapy whether it is given concomitantly, in a maintenance fashion, or both. In fact, the available data show a trend toward survival benefit with these strategies in some settings. Further follow-up will elucidate the effect of maintenance rituximab on long-term outcomes. For now, these initial data suggest that patients with indolent lymphoma might derive significant benefit from these novel therapeutic strategies.

Antibodies, Monoclonal↗
PubMed2005

Exploiting genotypic differences to identify genes important for EAE development.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of the human autoimmune disease multiple sclerosis (MS) and is primarily driven by T helper type 1 (Th1) cells. Interleukin (IL)-12 and interferon (IFN)-gamma are important cytokines involved in the differentiation and amplification of Th1 cells, however mice deficient in either IFN-gamma or IL-12 still develop EAE. We have used microarray analysis of EAE-affected CNS tissues in wild-type, IFN-gamma -/- and IL-12 -/- animals to identify genes critical for development of EAE. Over 500 genes were regulated in at least one genotype and over 94 genes were regulated in all three. Of those, 17 were also upregulated in spleen during the disease. We show that a majority of the genes regulated in EAE are also regulated in diseased regions of human MS tissues. The genes in the pool of 94 are more likely to be found regulated in MS patients than the genes regulated in only one or two of the mouse strains suggesting that analyzing gene expression under these multiple genetic conditions may lead to better identification of the genes critical for disease development.

Animals↗
PubMed2005

Re-treatment with I-131 tositumomab in patients with non-Hodgkin's lymphoma who had previously responded to I-131 tositumomab.

PURPOSE: To study efficacy and safety of re-treatment with I-131 tositumomab in patients with low-grade, follicular, or transformed low-grade B-cell lymphoma who relapsed following a response to I-131 tositumomab. PATIENTS AND METHODS: A prior response > or = 3 months to I-131 tositumomab was required. The single therapeutic dose following a dosimetric dose was adjusted to give the same total body dose (in Gy) as that used for the original dose, or was attenuated if the platelet count was less than 150,000 per mm(3) or if the prior treatment resulted in grade 4 cytopenias lasting longer than 7 days. RESULTS: Of 32 patients enrolled, 28 completed the therapeutic dose. A median of four therapies were given before re-treatment. Eighteen (56%) of 32 patients had a complete or partial response (median duration, 15.2 months); eight (25%) had a complete response (median duration, 35 months). Five continue in response from 1.8 to 5.7 years, with a median follow-up of 35 months. The overall median response duration was not significantly different for the two treatments, with no clinical factors predicting response or its duration. Ten of 18 re-responders had longer responses with re-treatment, with five having responses > or = 1.5 years longer. Grade 3/4 neutropenia and thrombocytopenia occurred in 50% and 43% of patients, respectively, similar to initial treatment. Antimouse antibodies developed in 10% of patients, and 12% developed elevated serum thyroid-stimulating hormone. Six patients were diagnosed with second malignancies, including four patients who developed myelodysplastic syndrome (one who had not received the therapeutic dose) and one with acute myelogenous leukemia. CONCLUSION: Re-treatment with I-131 tositumomab following a previous response can produce second responses that can be durable.

Adult↗