Maintenance Therapy with Decitabine in Younger Adults with Acute Myeloid Leukemia (AML) in First Remission: A Phase II Cancer and Leukemia Group B Study (CALGB 10503, Alliance)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 44-44 ◽  
Author(s):  
William Blum ◽  
Ben Sanford ◽  
Rebecca B Klisovic ◽  
Daniel J. DeAngelo ◽  
Geoffrey Uy ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Phase Ii ◽  
Residual Disease ◽  
Autologous Transplantation ◽  
Interleukin 2 ◽  
White Blood Count ◽  
High Dose ◽  
Aberrant Methylation ◽  
Free Survival ◽  
The Impact

Abstract Abstract 44 CALGB (now part of the Alliance for Clinical Trials in Oncology) performed a non-randomized phase II study testing one year (yr) of investigational maintenance therapy with decitabine for newly diagnosed adult AML patients (pts) <60 yrs of age (CALGB 10503, Alliance). The study included induction followed by molecular and cytogenetic risk-adapted consolidation identical to that given in the prior CALGB study for younger AML pts (19808). Induction used daunorubicin 90 mg/m2 for 3 days, etoposide 100 mg/m2 for 3 days, and cytarabine 100 mg/m2 for 7 days (3+3+7). Reinduction (2+2+5) was given for residual disease on day 14. Favorable risk pts [defined here as t(8;21), inv(16), or t(16;16)] in complete remission (CR) received 3 cycles of high dose cytarabine (HiDAC); all other pts received two-step consolidation with chemo-mobilization and autologous transplantation (autoHCT) if eligible, or HiDAC-based consolidation if not. However, removal from study for alloHCT in 1st CR, instead of the two-step autoHCT, was permitted for non-favorable risk pts. Maintenance decitabine began as soon as possible after recovery from consolidation; pts had to have CR with neutrophils >1 × 109/L, platelets >75 × 109/L, and be within 90 days after day 1 of the final consolidation. Decitabine 20mg/m2 was given IV over 1 hour for 4–5 days, every 6 weeks, for 8 cycles. 546 pts enrolled with a median age of 48 yrs (range, 17–60) and median presenting white blood count (WBC) of 12.6 × 109/L (range, 0.3–380 × 109/L). 75% achieved CR (412/546). Reasons for CR pts not receiving maintenance were mainly early relapse, alloHCT in 1st CR, inadequate count recovery, and patient refusal (Blum et al. ASH 2011). 33% of CR pts (134/412) received investigational maintenance. Of these, 46 (34%) were favorable risk; among the remaining 88 pts, 73 were consolidated with autoHCT, and 15 received HiDAC-based consolidation. The median time from initial study registration to initiation of maintenance therapy was 6.3 months. Pts receiving decitabine had a median age of 45 yrs (range, 18–60) and presenting WBC of 13.5 × 109/L (range, 0.4–221 × 109/L). Treatment with decitabine maintenance was feasible and reasonably well tolerated; the primary toxicity was myelosuppression. Preplanned dose reduction criteria for neutropenia were met after the first 20 pts had been treated. After this early timepoint, all subsequent pts who had been consolidated with autoHCT received only 4 days of decitabine per cycle (HiDAC consolidated pts continued to receive 5 days per cycle). The median number of cycles of decitabine received was 7 (range, 1–8); 46% of pts (62/134) received all 8 cycles, and 75% completed at least 4 cycles. Reasons for discontinuation of decitabine before completing 8 cycles included relapse (28%, 38/134), pt refusal (13%), adverse events (4%), and others. In this selected cohort of pts who received post-CR maintenance with decitabine, 1-yr and 3-yr overall survival (OS) were 96% and 66%; 1-yr and 3-yr disease-free survival (DFS) were 80% and 53%. 1-yr “failure-free survival” calculated from the time of registration to decitabine was 68% (70% for favorable risk, 68% for others). These results are similar to the outcomes for comparable pts enrolled on our prior CALGB study 19808 who received identical chemotherapy for induction and consolidation and then were randomized to observation or maintenance with interleukin-2 (3-yr OS 61% and 68%, 3-yr DFS 45% and 56%, for observation and IL-2 respectively). Post-consolidation maintenance with decitabine appears to provide only modest, if any, benefit overall. Correlative studies for CALGB 10503 are ongoing, including investigations into the impact of decitabine in unique molecular and cytogenetic subsets of disease, the prognostic/predictive value of aberrant methylation and other molecular markers, and assessment of minimal residual disease. Supported by CA33601 and CA128377. Disclosures: No relevant conflicts of interest to declare.

Minimal residual disease (MRD) status pre- and post- high-dose therapy/autologous stem (HDC/ASCT) cell transplantation for multiple myeloma (MM) in the era of novel agents.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8605-8605
Author(s):  
Adetola Kassim ◽  
Jeremy Scott McDuffie ◽  
Claudio A Mosse ◽  
Bipin N. Savani ◽  
John P. Greer ◽  
...  
Keyword(s):  
Residual Disease ◽  
Prognostic Significance ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Disease Stage ◽  
High Dose ◽  
Free Survival ◽  
Depth Of Response ◽  
The Impact

8605 Background: MRD assayed by multi-parameter flow cytometer (MFC), has prognostic significance after HDT/ASCT for MM (Paiva et. al. 2008). The frequency of MRD negativity (-) after induction therapy using novel agents such as immunomodulatory drugs like lenalidomide (IMiDs), and proteasome inhibitors like bortezomib, is unknown. The impact of HDT/ASCT on MRD status in this patient group has not been studied. Methods: We performed a retrospective study of all MM patients undergoing HDT/ASCT (January 2010 - December 2012) in our institution. No restrictions on inclusion were made based on the International Myeloma Working Group response criteria. All patients had novel agents as part of their initial induction regimen. Statistical analysis was by SPSS software (V 12.0). MRD status was determined by MFC on bone marrow samples pre- HDC/ASCT [M1] and post- HDC/ASCT (D100 [M2] and I year [M3]). MFC was done with antibodies against CD45, CD19, CD138, CD38, CD20, CD56, and anti-k and l cytoplasmic antibodies. Results: MRD status was available on 91 patients pre-transplant. Of these patients, 80 had MFC recorded at M2 and 17 patients had MFC recorded at M3. Fifty-eight percent were male and 76% were Caucasian. Forty percent received IMiDs, while 60% got proteasome based therapies. Of the 91 patients with MRD pre-HDC/ASCT, 58% (53/91) were MRD (-), and of these patients 89% (41/46) remained MRD (-) at M2. 48 patients were MRD positive (+) pre-HDC/ASCT, 58% (20/34) became MRD (-) at M2. Age, cytogenetic risk, disease stage, number of chemotherapy cycles or immunofixation status had no impact on MRD status. There were only 6 relapses in the cohort, thus the impact of MRD status on progression-free survival could not be studied. Conclusions: Novel agents improve depth of response pre-transplant. HDC/ASCT increases MRD negativity post-transplant. MRD status could aid better timing of HDC/ASCT or adoption of a risk-adapted strategy for high-risk patients. MRD status validation in a prospective cohort is underway at our center (NCT01215344). With future follow-up, the impact of MRD on progression-free survival in the era of novel agents will be determined.

Challenges for Conducting Clinical Trials Evaluating Maintenance Chemotherapy In Acute Myeloid Leukemia (AML): a Cancer and Leukemia Group B (CALGB) Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2176-2176 ◽  
Author(s):  
William Blum ◽  
Kate Donohue ◽  
Guido Marcucci ◽  
Daniel J DeAngelo ◽  
Geoffrey L Uy ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Residual Disease ◽  
Autologous Transplantation ◽  
Common Reason ◽  
Comprehensive Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Poor Risk ◽  
Frontline Therapy ◽  
One Year

Abstract Abstract 2176 Recent advances in frontline therapy for newly diagnosed AML include increased dose of anthracycline during induction, multi-agent regimens, high dose cytarabine (HiDAC) as consolidation for core binding factor (CBF) patients (pts), and allogeneic transplantation (alloHCT) during 1st remission for poor risk pts. Prolonged low-dose cytotoxic maintenance therapy does not appear to improve clinical outcomes, but investigation of novel maintenance strategies remains appealing, affording pts an opportunity to receive new therapies without increasing the considerable toxicities of induction/ consolidation. The CALGB performed a phase II study of induction and risk-adapted consolidation, followed by one year of maintenance therapy with decitabine, for newly diagnosed AML pts <60 years of age (CALGB 10503). Induction was daunorubicin 90 mg/m2 for 3 days, etoposide 100 mg/m2 for 3 days, and cytarabine 100 mg/m2 for 7 days (3+3+7). Reinduction (2+2+5) was given for residual disease on day 14. CBF pts in CR received 3 cycles of HiDAC; all other pts received autologous transplantation (autoHCT) if eligible, or HiDAC if not. Poor risk pts in 1st CR received alloHCT off study, when appropriate. Maintenance decitabine (20mg/m2 intravenously for 4–5 days, every 6 weeks for 8 cycles) began within 60–90 days after consolidation for pts with neutrophil ≥1000/uL and platelets ≥75,000/uL. Clinical results for the efficacy of decitabine maintenance for one year are not yet mature; the study closed to accrual July 30, 2010. In a previous study for a slightly more favorable patient cohort that was treated with identical induction and consolidation (CALGB 19808), 29% of all enrolled pts (214/732) and 39% of CR pts were registered to a randomized investigational maintenance therapy. To examine the feasibility of conducting a subsequent randomized trial of maintenance therapy, we analyzed reasons for study discontinuation for all pts enrolled on CALGB 10503; 473 pts had “response” or “off study” data forms submitted, to date. Complete remission* (CR) was achieved in 349 (74%). Reasons for induction failure were primary refractory AML (15%), induction death (5%), and other (6%, including those withdrawn from protocol for alternative therapy presumably due to persistent disease). The most common reason for not receiving maintenance therapy was the presence of AML, either primary refractory as noted or early relapse (7% of CR pts). In pts who achieved CR, the most common reason for not receiving maintenance was removal from the protocol for alloHCT (71/349, 20%). 9% refused further protocol therapy after consolidation, perhaps from “treatment fatigue.” Correlative investigations for CALGB 10503 are ongoing, including identification of novel prognostic markers, targets for treatment, and markers of minimal residual disease. Clearly, clinical investigation of maintenance therapy as part of a comprehensive treatment approach for frontline therapy of AML (inclusive of homogeneous induction and consolidation therapy) requires considerable up-front enrollment in order to reach maintenance accrual goals. Randomized maintenance studies will likely need intergroup participation for timely completion. However, we conclude that the benefits of up-front enrollment (relative to a post-consolidation enrollment strategy) outweigh the accrual burdens. Benefits include uniform pre-maintenance therapy and the potential for novel discovery from correlative studies. Study designs for future maintenance trials for AML in 1st CR must balance expediency with the more comprehensive approach employed in CALGB 10503. Disclosures: Blum: Celgene: Research Funding. Off Label Use: decitabine in AML. DeAngelo: Deminimus: Consultancy.

Leopard: A Phase II Study Of Post Autologous Stem Cell Transplantation (ASCT) Maintenance Lenalidomide and Prednisolone For Myeloma (MM), Incorporating Minimal Residual Disease (MRD) Assessments

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3223-3223
Author(s):  
Anna Kalff ◽  
Nola Kennedy ◽  
Patricia A. Walker ◽  
Marion Black ◽  
Odette Youdell ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Minimal Residual Disease ◽  
Phase Ii ◽  
Residual Disease ◽  
High Dose ◽  
Poor Risk ◽  
Depth Of Response ◽  
Best Response ◽  
Grade 3 ◽  
Minimal Residual

Abstract Background Despite improved outcomes achieved with high dose melphalan conditioned ASCT for MM patients, relapse is inevitable. Consolidation/maintenance therapy with novel agents following ASCT can prolong progression free (PFS) and overall survival (OS) as well as further improve depth of response, the latter being associated with superior survival. More sensitive techniques are now available to monitor minimal residual disease (MRD). Aim To document disease response changes in MM patients receiving maintenance lenalidomide and alternate-day prednisolone (RAP) after a single ASCT. To sequentially quantify MRD in those patients achieving an immunofixation negative (IF-) complete response (CR) utilizing freeLite chain (FLC), hevyLite chain (HLC, in patients with intact IgG or IgA immunoglobulin) and multiparameter flow cytometry (MFC). To assess PFS/OS and safety/tolerability. Methods Phase II, open label, single arm, multi-center study. Newly diagnosed patients with MM were commenced on RAP (lenalidomide 10mg/continuous daily increasing to 15mg after 8 weeks and alternate day prednisolone 50mg) 6-8 weeks after a single MEL200 ASCT as part of first-line therapy. RAP was continued until unacceptable toxicity or relapse/progression. Serum for FLC/HLC was collected every 2 months. Patients achieving an IF- CR had serial BMATs for MFC. This is an interim analysis of the first 30 of a total of 60 patients recruited to the study. Results This analysis included 30 patients (M 17, F 13), median age 61 years (range 46-71), ISS stage I: 11, II/III: 19. 27 patients had diagnostic cytogenetics +/- FISH performed - 10 had poor risk features (t(4;14), t(14;16), del17p, del13 and/or +1q). After a median 549 days (range 385-768), 16 patients remain on therapy. Median PFS was 470 days (range 64-768), median OS was 514 days (range 247-768). Discontinuation was due to relapse/progressive disease in 8, AEs in 5 and poor compliance in 1. 4 patients have died; 3 due to MM and 1 due to therapy related AML [tAML]. The best achieved overall response rate (ORR) was 100%, with 19 IF- CR (63%) (13 stringent CR [sCR]), 10 VGPR (33%) and 1 PR (3%). 16 patients demonstrated an enhanced response while on RAP, including conversion to CR (n=3) or sCR (n=10) (6/10 were MFC negative [MFC-]). Median time to achieving best response was 111 days (range 28-287). 18 patients who achieved IF- CR had MFC studies and 11 were MFC-: of these 11, 5 had normal (FLC-) and 6 abnormal (FLC+) FLC ratios. Five of the 18 were MFC+, 4 of whom were FLC- and have not relapsed. Two of the 18 fluctuated between MFC+ and MFC-. Seven IF- CR patients had HLC analysis; 5/7 patients were MFC- in all samples, 3 of which also had normal HLC ratios (HLC-) and were FLC-. 2/7 patients were MFC+/HLC-. 10 patients relapsed/progressed after a median of 229 days (64-621), 5 from IF- CR (3 sCR). 5/8 with diagnostic cytogenetics had poor risk features, all with +1q in addition to other abnormalities. 3/19 remaining patients with cytogenetics who did not progress have +1q, suggesting a trend (p=0.07) to worse PFS in those with 1q+. In those who relapsed from IF- CR: 2 converted from MFC- to MFC+ prior to relapse/HLC-, 1 was FLC+ and 1 converted to FLC+ at relapse; 2 were MFC-/FLC- converting to FLC+ at relapse; 1 was MFC+/FLC+). All grade haematologic AEs comprised thrombocytopenia 7/30 (23%) (grade 3/4: 4), neutropenia 2/30 (grade 3: 1) and anaemia 3/30(grade 3: 1). All grade non-haematologic adverse events regardless of relatedness to study treatment (>10%) were: infections (URTI: 53%, LRTI: 23%, VZV reactivation: 23%, UTI: 13%), diarrhoea (37%), fatigue (27%), muscle cramps (23%), insomnia (23%), mouth ulcers (13%), peripheral oedema (13%). There was 1 second primary malignancy (SPM) - tAML. This occurred 461 days after commencing RAP. AEs leading to discontinuation were thrombocytopenia (3 patients), central retinal vein thrombosis and tAML. 11 patients tolerated lenalidomide dosing as per protocol, 6 were not increased from 10 to 15mg, 8 required dose modification for AEs (6 to 10mg; 2 to 5mg) and 5 were discontinued due to AEs. Conclusion RAP maintenance improved depth of response post-ASCT with some achieving best response > 8 months after initiation. ORR was 100%, with high rates of CR (20%) and sCR (43%). Correlation between MFC and serological testing appears poor. Many patients who relapsed had poor-risk cytogenetics (+1q), suggesting that these patients may benefit less from RAP maintenance. Disclosures: Off Label Use: Lenalidomide not approved for maintenance therapy post ASCT in Australia. Spencer:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Requirements for operational cure in multiple myeloma

Blood ◽  
2021 ◽  
Author(s):  
Mohamad Mohty ◽  
Hervé Avet-Loiseau ◽  
Jean-Luc Harousseau
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Limit Of Detection ◽  
Autologous Transplantation ◽  
Significant Proportion ◽  
Response To Treatment ◽  
High Dose ◽  
Duration Of Treatment ◽  
The Impact

Multiple myeloma is usually considered as an incurable disease. However, with the therapeutic improvement observed in the last few years, achievement of an "operational" cure is increasingly becoming a realistic goal. The advent of novel agents, with or without high-dose chemotherapy and autologous transplantation, uncovered a correlation between the depth of response to treatment and the outcome. Of note, minimal residual disease (MRD) negativity is increasingly shown to be associated with improved progression-free survival (PFS), and MRD status is becoming a well-established and strong prognostic factor. Here, we discuss the impact of MRD negativity on PFS and long-term disease control, as a surrogate for a potential cure in a significant proportion of patients. The MRD value and impact should be examined by focusing on different parameters: (i) sensitivity or lower limit of detection level (method used); (ii) timing of assessment and sustainability (iii) type and duration of treatment; (iv) initial prognostic factors (most importantly, cytogenetics) and (v) patient age. Currently, the highest probability of an operational cure is in younger patients receiving the most active drugs, in combination with autologous transplantation followed by maintenance therapy. Older patients are also likely to achieve operational cure, especially if they are treated upfront with an anti-CD38 antibody-based therapy, but also with novel immunotherapies in future protocols. The incorporation of MRD as a surrogate endpoint in clinical trials, would allow the shortening of these, leading to more personalised management, and achievement of long-term cure.

scholarly journals Maintenance therapy in multiple myeloma

2016 ◽  
Vol 8 (2) ◽  
pp. 71-79 ◽  
Author(s):  
Prerna Mewawalla ◽  
Abhishek Chilkulwar
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Residual Disease ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
Complete Response ◽  
Novel Agents ◽  
Free Survival ◽  
Incurable Disease

Despite recent advances, multiple myeloma remains an incurable disease. Induction therapy followed by autologous transplantation has become the standard of care. The idea of maintenance therapy in multiple myeloma is not new. Starting with chemotherapy in 1975, to interferon in 1998, to novel agents recently, a multitude of agents have been explored in patients with multiple myeloma. In spite of the novel agents, multiple myeloma continues to be an incurable disease with the progression-free survival after autologous transplant rarely exceeding 3 years. The goal of using maintenance therapy has been to improve the outcomes following autologous transplantation by increasing the progression-free survival, deepening remissions and perhaps increasing overall survival. It has been shown that patients with a stringent complete response (CR) have a better outcome [Kapoor et al. 2013]. It is becoming increasingly common to check minimal residual disease (MRD) as a means of assessing depth of response. It has also been shown that patients with no MRD have not only a better progression-free survival but also a better overall survival compared with patients who are MRD positive. This makes it even more important to find agents for maintenance therapy, which can further deepen and maintain responses. Here, we present a comprehensive review of the agents studied as maintenance for multiple myeloma and their efficacy, both in terms of overall survival, progression-free survival and toxicity.

scholarly journals Long-term progression-free survival of patients with metastatic melanoma or renal cell carcinoma following high-dose interleukin-2

2021 ◽  
Vol 69 (4) ◽  
pp. 888-892
Author(s):  
Joseph I Clark ◽  
Brendan Curti ◽  
Elizabeth J Davis ◽  
Howard Kaufman ◽  
Asim Amin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Melanoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.

High-dose busulfan and cyclophosphamide with autologous bone marrow transplantation support in advanced malignancies in children: a phase II study.

1986 ◽  
Vol 4 (12) ◽  
pp. 1804-1810 ◽  
Author(s):  
O Hartmann ◽  
E Benhamou ◽  
F Beaujean ◽  
J L Pico ◽  
C Kalifa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Phase Ii ◽  
Marrow Transplantation ◽  
Residual Disease ◽  
Phase Ii Study ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Terminal State ◽  
High Dose

Twenty children with advanced, nonleukemic malignancies entered a phase II study of high-dose busulfan-cyclophosphamide followed by bone marrow transplantation (BMT). All had disease refractory to conventional and/or high-dose chemotherapy (HDC). There were ten neuroblastoma patients, six non-Hodgkin's lymphoma, three Ewing's sarcoma, and one rhabdomyosarcoma. Eight had primarily resistant disease, ten were in second progressive relapse, and two in third progressive relapse. One patient was not evaluable for response. Among the 19 evaluable patients the responses observed were complete response (CR), seven; partial response (PR), three; objective effect, five; and failure, four. However, survival was poor: 15 patients died, two are alive with disease, and three are alive with no evidence of disease (NED) at 8+, 11+, 14+ months post-BMT. Toxicity was high but considered as acceptable, taking into account the terminal state of these patients. Seven treatment-related deaths were observed. This combination therapy proved to be highly effective, with a response rate of 50%, and its value for eradication of residual disease in less advanced patients should be investigated.

Does interleukin-2 have a role in the management of acute leukemia?

1993 ◽  
Vol 11 (9) ◽  
pp. 1817-1825 ◽  
Author(s):  
R Foa
Keyword(s):  
Acute Leukemia ◽  
Residual Disease ◽  
Therapeutic Option ◽  
Interleukin 2 ◽  
Leukemia Cell ◽  
Retroviral Vectors ◽  
High Dose ◽  
Functional Changes ◽  
Leukemia Cell Lines ◽  
Infusion Protocol

PURPOSE To discuss the possibility that interleukin-2 (IL-2)-based immunotherapeutic protocols may have a role in the management of acute leukemia. DESIGN The preclinical results that have led to the clinical use of IL-2 in acute leukemia will be reviewed. The clinical data obtained with the administration of IL-2 to acute leukemia patients in different phases of their disease will be discussed, together with the clinicohematologic and immunologic modifications induced following the infusion of IL-2. Finally, the possibility that limitations associated with the exogenous administration of high-dose IL-2 may be circumvented by engineering techniques aimed at inserting the IL-2 gene directly into the tumor cells, will be addressed. RESULTS The data indicate that high-dose IL-2 may be administered to acute leukemia patients. Toxicity, recorded in all patients, appears to be controllable using a continuous intravenous (i.v.) infusion protocol based on a daily dose-escalating administration. Complete remissions have been documented in acute myeloid leukemias (AMLs) with a limited, but detectable proportion of residual marrow blasts. Numerous phenotypic and functional changes have been recorded within the immune system of the host. Using retroviral vectors, the IL-2 gene may be productively transduced into human acute leukemia cell lines. CONCLUSION IL-2 appears to represent a therapeutic option for AML patients with limited/minimal residual disease. The results of the ongoing randomized trials in patients in first or second remission are awaited.

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