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Brief-Duration High-Intensity Chemotherapy for Patients With Small Noncleaved–Cell Lymphoma or FAB L3 Acute Lymphocytic Leukemia: Results of Cancer and Leukemia Group B Study 9251

From the Department of Medicine, the Alvin and Lois Lapidus Cancer Institute, Sinai Hospital, Baltimore, MD; Cancer and Leukemia Group B Statistical Center, Durham, NC; Georgetown University, Washington, DC; Roswell Park Memorial Institute, Buffalo; New York University Medical Center, New York, NY; Ohio State University, Columbus, OH; University of Minnesota, Minneapolis, MN; and Karmanos Cancer Institute, Wayne State University, Detroit, MI.

Address reprint requests to Charles A. Schiffer, MD, Wayne State University School of Medicine, 3990 John R, Harper Hospital, 5 Hudson, Detroit, MI 48201; email: schiffer{at}karmanos.org

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
PURPOSE: To define the activity and feasibility of brief-duration high-intensity chemotherapy for adults with small noncleaved, non-Hodgkin’s lymphoma (SNC) and the L3 variant of acute lymphocytic leukemia (L3 ALL).

PATIENTS AND METHODS: Seventy-five adults with either SNC or L3 ALL (median age, 44 years) were treated with an aggressive regimen that consisted of one cycle of cyclophosphamide and prednisone followed by cycles containing either ifosfamide or cyclophosphamide; high-dose methotrexate, vincristine, dexamethasone, and either doxorubicin or etoposide/cytarabine; or intrathecal triple therapy with prophylactic CNS irradiation.

RESULTS: All 24 patients with L3 ALL and the 30 of 51 patients with SNC confirmed by central histologic review were included in this analysis. Forty-three of 54 patients achieved complete response (CR) (18 of 24 with ALL and 25 of 30 with SNC), and 28 are alive and in continuous CR with a median follow-up of 5.1 years. Hematologic toxicity was profound, and nonhematologic toxicity was notable, with 10 of 75 patients treated developing significant neurologic toxicity consisting of transverse myelitis in five patients, CNS toxicity in three, and severe peripheral neuropathy in two. All patients who did not achieve CR died of the disease, and all recurrences occurred within 16 months of the end of treatment. Responses and toxicities were similar in the patients with both lymphoma and leukemia.

CONCLUSION: Aggressively delivered chemotherapy is potentially curative in as many as half of patients with SNC and the L3 ALL variant. This treatment regimen had considerable neurologic toxicity and has been modified.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
APPROXIMATELY 3% of adults with acute lymphocytic leukemia (ALL) have so-called Burkitt’s leukemia.¹ This form of ALL, characterized by the French-American-British terminology as FAB L3, usually has a distinct morphologic appearance with cytoplasmic vacuolization and is characterized by B-cell lineage, the presence of surface immunoglobulin by flow cytometry, the absence of terminal deoxynucleotidyl transferase, and a propensity for CNS involvement. These patients often have balanced cytogenetic translocations involving the myc gene locus on chromosome 8 and one of the three loci involved with immunoglobulin synthesis, most commonly the heavy chain locus on chromosome 14, which results in a translocation between chromosomes 8 and 14 at bands 8q24 and 14q32. Although these patients may enter complete remission with standard ALL therapy, they are rarely, if ever, cured with such approaches.

Among adults with non-Hodgkin’s lymphoma (NHL), a similarly small fraction have small noncleaved cell NHL (SNC) of either the Burkitt’s or non-Burkitt’s types (International Working Formulation category J) now called Burkitt’s or Burkitt’s-like lymphoma in the Revised European-American Lymphoma classification.² This entity is a biologically aggressive disease that does not respond as well to the type of chemotherapy that is frequently curative in patients with large-cell lymphomas. Such patients often have rapidly growing tumors with a high frequency of extra-nodal disease, such as marrow involvement.

Morphologically, cytogenetically, and immunophenotypically, SNC NHL and the L3 variant of ALL share many of the same characteristics. Although the diagnosis tends to be made cytologically for patients with L3 and made histologically for patients with SNC, there is a spectrum of disease extending between patients with lymph node involvement and normal bone marrow to those without adenopathy and with extensive marrow involvement. This is analogous to the overlapping clinical features found in patients with lymphoblastic lymphoma and T-cell ALL.

Recently, a series of publications conducted primarily in children and adolescents has documented high response and survival rates in patients with these diseases when they are treated with relatively short-term high-dose therapy administered in repetitive cycles. There is less experience in the treatment of adults. Therefore, the Cancer and Leukemia Group B (CALGB) chose to adapt a regimen, previously piloted in Germany in patients with FAB L3 ALL,³ to treat patients with either FAB L3 ALL or patients with SNC in a phase II study. This regimen, reported in detail by Hoelzer et al,³ was based on the combination of an alkylating agent (either cyclophosphamide or ifosfamide) administered for 5 days with high-dose methotrexate, aggressive intrathecal chemotherapy, and CNS irradiation. Alternate cycles contained either cytarabine and teniposide or doxorubicin. For the purposes of treating patients in the United States, we changed the teniposide to etoposide, the cytarabine from subcutaneous injections to a 48-hour infusion, and substituted intrathecal hydrocortisone for intrathecal dexamethasone.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
Eligibility Criteria
Adults were eligible for entry onto this trial provided that a diagnosis of either SNC or the L3 form of ALL had been made. Patients with SNC were required to have measurable disease that had been quantified by physical examination and appropriate computed tomography scans. Patients with more than 25% involvement of bone marrow were considered to have L3. No prior treatment was permitted other than hydroxyurea for hyperleukocytosis. Other eligibility requirements included relatively normal hepatic and renal function (bilirubin and creatinine < 1.5 x upper limit of normal) unless abnormal function was attributable to leukemia or lymphoma. Patients were screened for risk factors for HIV disease, but a test for HIV was not required. Patients who were known to be HIV-positive were ineligible for the protocol. The protocol was reviewed and approved by local institutional review boards, and written informed consent was obtained from each patient.

Central Review of Diagnosis
All patients were required to have pathologic material submitted for review by CALGB pathologists. All patients with SNC had slides submitted for expedited review, which allowed for patients to have protocol-directed treatment discontinued and more standard regimens initiated if central review did not confirm SNC. Additionally, patients with marrow disease were required to have cells (marrow or blood if appropriate) submitted for central immunophenotyping and cytogenetic studies.

Statistical Methods
It was assumed that the number of patients with SNC would be significantly greater than the number of L3 patients, and, therefore, the study was designed as a mini-max two-stage phase II study for SNC patients and as a single-stage pilot study for L3 patients. For SNC patients, the study was designed with an early stopping rule to assess whether the data indicated a complete remission rate of approximately 80%. Study parameters included accrual of 26 and 19 eligible SNC patients onto the first and second stages, respectively, a 5% type I error, and 90% power to test the alternative of an 80% remission rate. Similar design parameters were used for the L3 patients once it became evident that more L3 patients were being accrued to the study than expected.

Survival time was measured from study entry to death from any cause. Treatment failure was measured from study entry to first evidence of disease progression, disease recurrence, or death from any cause. Time-to-event distributions were estimated by the product-limit method. Proportional hazard models were used to investigate the simultaneous association of prestudy patient characteristics on survival and time to treatment failure.

Treatment Regimen
The treatment program for the first 75 patients is listed in Table 1. All patients received an initial 5-day course of cyclophosphamide and prednisone intended to reduce the likelihood and severity of tumor lysis syndrome. Beginning on day 8, they received alternating cycles of two multidrug regimens at 3-week intervals

Evaluation and Response Criteria
For all patients, assessment of all known areas of disease was required to define response. Computed tomography scans in patients with lymphoma were required with alternate courses of therapy, as were bone marrow examinations in patients with L3. Patients with SNC were required to demonstrate resolution of measurable disease and bone marrow findings if abnormal. Complete response (CR) was defined as the resolution of all disease on examination and on scan, and partial response (PR) was defined as a greater than 50% reduction in the sum of products of the cross-sectional diameters of all measurable lesions. Relapse was defined by the reappearance of adenopathy or marrow relapse according to standard definitions.

Data Audit
As part of the quality-assurance program of the CALGB, members of the Data Audit Committee visit all participating institutions at least once every 3 years. The auditors verify compliance with federal regulations and protocol requirements, including those pertaining to eligibility, treatment, toxic effects, tumor response, and outcome in a sample of protocols at each institution. Such on-site review of medical records was performed for a randomly selected subgroup of 32 (43%) of the 75 patients treated under this study.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
The interim analysis of the data indicated that accrual onto the second stage was appropriate on the basis of observed remission rates. However, severe neurologic toxicity was observed, which required that the regimen be modified to reduce the CNS treatment. Therefore, this report includes all 30 eligible SNC patients who received the initial protocol treatment before the treatment amendment, and all the L3 patients were accrued during this period. CALGB study 9251 accrued 75 patients between 1992 and 1996. As of January 29, 2001, the median duration of follow-up for surviving patients was 5.1 years (range, 3.4 to 7.9 years).

Pathologic Review and Cytogenetic Studies
L3 ALL. Of the 24 patients with ALL, 19 submitted specimens for cytogenetic analysis at diagnosis. Of these 19, eight had the typical t(8;14)(q24;q32), and one had the typical variant t(2;8)(q24;q32). Three additional patients had complex karyotypes with no evidence for the t(8;14) or its variants. Of the remaining seven patients, no mitoses were available from one case, two cases had only blood submitted that was normal cytogenetically, and four patients had bone marrow cytogenetic evaluations that were normal.

Of the 15 patients who did not have the typical t(8;14), three had immunophenotyping results consistent with L3 ALL (monoclonal light chains). Of the remaining 12 patients, central morphologic review agreed with the diagnosis of L3 ALL in eight patients. Two patients had ALL L2 by central review, and two did not have adequate specimens submitted for central review. Thus, 20 of 22 patients with central pathology review had either L3 morphology or typical cytogenetic or flow cytometry findings. All 12 patient whose diagnosis was confirmed by cytogenetics or flow cytometry had L3 morphology. All 24 patients are included in the analysis.

SNC. Of the 51 patients registered with SNC, two were considered ineligible. One had received prior therapy (radiation to the CNS just before the start of treatment), and one was registered but found not to have SNC at the local institution before starting treatment. Central review of pathologic material confirmed the diagnosis in 30 of 49 patients and was discordant in 19. The centrally reviewed diagnoses for these 19 patients were diffuse large-cell lymphoma, 11 patients; large-cell immunoblastic lymphoma, three patients; follicular and diffuse large-cell lymphoma, two patients; unclassifiable, three patients. Many of these patients had their treatment modified to more conventional regimens at the discretion of the local institution after the results of the central review were communicated.

Patient Population
The demographic details for the subgroups of 30 patients with SNC and 24 with L3 ALL are presented in Table 2. The median age of this group of patients was 44 years. Thirty-five percent of patients were 50 years of age, and 19% were 60 years of age. There was a preponderance of males in the L3 group, and all of the L3 patients had elevated lactate dehydrogenase values. Two of 54 patients, both with L3 ALL, had CNS involvement either at diagnosis or at the time of the first specified lumbar puncture on day 8 of treatment.

As listed in Table 3, 80% of patients (43 of 54) treated on this study experienced CRs, and 9% experienced PRs. The CR rate was 75% in the L3 patients and 83% in the pathologically eligible SNC patients (73% in the total group of SNC patients). Overall survival and failure-free survival (FFS) for all patients are shown in Fig 1. Thirty-one of these 54 patients (57%) received all seven planned courses of treatment (Table 4). Disease progression was the most frequent reason for the discontinuation of treatment.

View larger version (13K): [in this window] [in a new window]   Fig 1. Survival and FFS for all 54 eligible patients treated on CALGB 9251.

View larger version (12K): [in this window] [in a new window]   Fig 2. Survival and FFS for the 24 patients with L3 ALL treated on CALGB 9251.

View larger version (13K): [in this window] [in a new window]   Fig 3. Survival and FFS for the 30 patients with SNC NHL treated on CALGB 9251.

Toxicity was similar for the patients with SNC and L3 ALL, and the side effects, presented as the percent of patients experiencing a particular event, have, therefore, been pooled for all patients and are listed in Table 5. There was significant hematologic toxicity, with 93% of patients achieving grade 4 neutropenia and 85% achieving grade 4 thrombocytopenia at some time during their course of treatment. Hematopoietic growth factors were not used in this protocol. Mucosal toxicity was also noted, with 32% of patients experiencing grade 4 stomatitis, and 16%, grade 4 esophagitis.

There were 32 deaths (of the 74 patients who began treatment) as a consequence of treatment and/or disease. There were four (7%) deaths in the 54 eligible patients as a consequence of treatment and its toxicity between days 3 and 105. Of these four deaths, one occurred after course 2 before a response could be determined, one occurred after course 4 in a patient who had achieved CR, and two occurred in patients whose best response was a PR. Among the patients who were histologically found not to have SNC, there were three deaths that occurred before relapse. One occurred within 12 hours of the initiation of chemotherapy, and the others occurred after two cycles of treatment. Thus, seven patients who were treated died of treatment-related complications, with six of these related to infection and the other to a hemothorax. In all other patients, death occurred after relapse, disease progression, or nonprotocol treatment.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
Until the reports from Germany³ and more recently from the M.D. Anderson Cancer Center,⁴ no published data suggested that the L3 variant of ALL was a curable disease in adults. The results of CALGB protocol 9251 in adults with either SNC lymphoma or L3 ALL demonstrate that a significant fraction of patients enjoy prolonged disease-free survival after treatment with intensive regimens in which the therapy is administered over a relatively short period of time. In our series, 80% of patients with L3 or SNC achieved complete remission, and long-term disease-free survival was documented in approximately half of the patients with either L3 or SNC.

The use of shorter, intensive regimens without maintenance therapy derives from studies done in children, in whom SNC lymphoma represents the most common histologic subtype. Patte et al⁵ demonstrated the utility of the LMB regimen in children (median age, 6 years) in a randomized trial that compared a shorter regimen with the same treatment followed by a maintenance phase, clearly showing that more prolonged therapy did not increase the cure rate. Long-term event-free survival was achieved in 68% of children with L3 or stage IV SNC, with better results in earlier-stage patients. In a subsequent report, the same group treated 65 younger adults (median age, 26 years) with the same regimen; 89% achieved CR, and 47 of 65 remain free of recurrence.⁶

Magrath et al⁷ have also reported on the results of treatment of both children and adults with SNC. In the most recent study, 21 children and 20 adults were treated with an intense and complex regimen similar to that used in CALGB 9251 but with a greater dose-intensity. No differences were found in this study between adults and children. Thirty-nine of 41 patients entered CR, and event-free survival was 92% at 2 years. However, the median age of the adults was 25 years, and only three had stage IV disease. Only nine of the 54 patients evaluated for response in our series had early-stage (stage I or II) disease.

The results of CALGB 9251 are remarkably comparable with other results reported in the literature for adults with L3 ALL (Table 6). Hoelzer et al³ and Thomas et al⁴ also noted overall survival rates of approximately 50% in older adults with L3 ALL (median ages ranged from 35 to 58 years). The survival curves in all these studies were identical, with few relapses occurring more than 1 year after treatment. The regimens used in the CALGB 9251 and Hoelzer et al³ reports were similar, with considerable overlap in the agents used with the hyper C-VAD treatment reported by Thomas et al.⁴ Longo et al⁸ reported on outcome in patients retrospectively determined to have SNC after treatment on prednisone, methotrexate, doxorubicin, cyclophosphamide, and etoposide–based regimens. The median age was 36 years, somewhat older than that of some of the other adult studies, but only 10 of the 33 patients had stage IV disease, and none had L3. Nonetheless, 60% of patients were long-term survivors.

As noted in our study, there is also difficulty in reproducibly classifying Burkitt’s and Burkitt’s-like lymphomas,⁹ with particular confusion in adults with diffuse large-cell lymphoma. There may also be variability at the molecular level in the disruption of the myc gene and its product, in the role of the Epstein-Barr virus, and in mutations in the p53 gene.¹⁰ Although it is possible that with molecular techniques more patients might have been shown to have a typical Burkitt’s rearrangement, it is also clear that many patients treated on the published trials do not have mutations involving myc. In the National Cancer Institute series, none of 11 patients with what was termed non-Burkitt’s SNC had c-myc rearrangements, although 17 of 18 with sporadic Burkitt’s lymphoma had rearangements.¹¹ An analysis of 39 patients who had an abnormal karyotype and were treated in Vancouver for SNC non-Burkitt’s found 11 individuals with myc rearrangements, 15 without a rearrangement, and another 13 with dual translocations involving both myc and the bcl-2 gene.¹² This distribution of c-myc abnormalities would undoubtedly be different than in other studies, because successful karyotyping was a requisite for inclusion. The patients received a heterogeneous melange of therapies, with the best outcome seen in the patients with myc rearrangement alone, who were also somewhat younger, and the poorest in patients with dual rearrangements. Thus, the heterogeneity in diagnostic criteria and the differing biology in patients with or without myc and other gene rearrangements¹³ may explain some of the differences in outcomes among the different series and perhaps between patients of different ages.

Another possibility is that younger patients tolerate higher doses of chemotherapy. Magrath et al’s data⁷ suggest that the same doses of chemotherapy produce similar outcomes in adults and children. No differences in outcomes were seen between children and adults, but the adults in that series were 2 decades younger than our patients were. Although almost 90% of the patients in our study completed at least four courses of treatment, older patients more than 50 years of age were much less likely to receive the full scheduled treatment because of both toxicity and disease progression. All of the published regimens use similar chemotherapeutic agents, although with differences in schedule and sequence. In the absence of randomized trials, it is impossible to pinpoint variations in treatment programs that possibly account for differences in outcome.

Studies of marrow transplantation in SNC/L3 ALL have also been reported, with approximately 70% of patients in first complete remission remaining free of disease long-term.¹² These results are not an improvement on the results reported here, given the complete remission rate associated with this and other induction chemotherapy regimens. However, marrow transplantation seems to be an appropriate treatment for recurrence, because the European group reported 30% long-term survival in this group of patients.¹⁴ Because of the rapid rate of tumor growth in patients who experience relapse, it is often difficult to arrange for transplantation approaches for such patients. There have not been systematic studies monitoring patients for signs of minimal residual disease or early relapse. Given the significant relapse rate in adults, such studies, with an attempt to provide early transplantation, would be of interest.

On the basis of the results of the series treated by Hoelzer et al³ in the German group, we used aggressive CNS prophylactic therapy modeled on their protocol. Whereas only two patients in Hoelzer’s group developed CNS recurrence, this approach proved overly toxic in our patient population. The concomitant administration over a short interval of high-dose methotrexate, intermediate-dose infusional cytarabine, intrathecal methotrexate, cytarabine, and hydrocortisone, and cranial irradiation was associated with an excessive rate of intolerable and sometimes irreversible neurologic changes. The National Cancer Institute group also reported a syndrome of severe neurologic toxicity but found this to be reversible.¹⁵ It may be that the patterns of toxicity differ in different age groups as well as with different treatment regimens. As a consequence, we have modified our approach to CNS prophylaxis. We currently reserve cranial irradiation for those patients with marrow or CNS disease, beginning the irradiation after the completion of chemotherapy, and have reduced the number of doses of intrathecal chemotherapy from two with each of cycles 2 to 7 to one with each cycle (12 doses reduced to six doses). Preliminary evaluation of a subsequent cohort of patients suggests that the frequency and severity of neurologic problems has decreased substantially.¹⁶

The similarity of response to the same treatment regimen in our study further consolidates the impression that SNC and L3 are differing expressions of the same disease. Future studies of SNC and L3 ALL should be open to patients with either diagnosis. It is also clear, however, that these are biologically heterogeneous disorders. Future studies should incorporate molecular analyses to more effectively characterize the disorders being treated and to identify patients less likely to benefit from this type of treatment so that new approaches may be tested. Retrospective analyses that use archived tissue from patients on these already completed studies may also be quite instructive in this regard. The role of bone marrow transplantation in subgroups of patients or at the time of treatment failure or early relapse, as well as the possibility of lesser treatment for early-stage disease is, as yet, unclear.

	APPENDIX

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 

	ACKNOWLEDGMENTS

 
Supported in part by grant no. CA31946 from the National Cancer Institute. Additional grant information is included in the Appendix.

	NOTES

 
Contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX REFERENCES

 
1. Bennett JM: Classification of the acute leukemias: Cytochemical and morphologic considerations, in Wiernik PH, Canellos GP, Kyle RA, et al (eds): Neoplastic Diseases of the Blood, ed 2. New York, NY, Churchill Livingstone Inc, 1991, pp 169-181

2. Jaffee ES: Pathology of malignant lymphomas, in Wiernik PH, Canellos GP, Kyle RA, et al (eds): Neoplastic Diseases of the Blood, ed 2. New York, NY, Churchill Livingstone Inc, 1991, pp 631-661

3. Hoelzer D, Ludwig W, Thiel E, et al: Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87: 495-508, 1996[Abstract/Free Full Text]

4. Thomas DA, Cortes J, O’Brien S, et al: Hyper-CVAD program in Burkitt’s type adult acute lymphoblastic leukemia. J Clin Oncol 17: 2461-2470, 1999[Abstract/Free Full Text]

5. Patte C, Philip T, Rodary C, et al: High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: Results from the French Pediatric Oncology Society of a randomized trial of 216 children. J Clin Oncol 9: 123-132, 1991[Abstract/Free Full Text]

6. Soussain C, Patte C, Ostronoff M, et al: Small noncleaved cell lymphoma and leukemia in adults: A retrospective study of 65 adults treated with the LMB pediatric protocols. Blood 85: 664-674, 1995[Abstract/Free Full Text]

7. Magrath I, Adde M, Shad A, et al: Adults and children with small noncleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol 14: 925-934, 1996[Abstract/Free Full Text]

8. Longo D, Duffey P, Jaffe E, et al: Diffuse small noncleaved cell-cell, non-Burkitt’s lymphoma in adults: A high-grade lymphoma responsive to ProMACE-based combination chemotherapy. J Clin Oncol 12: 2153-2159, 1994[Abstract/Free Full Text]

9. Harris NL, Jaffe ES, Stein H, et al: A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study group. Blood 84: 1361-1392, 1994[Free Full Text]

10. Gutierrez MI, Bhatia K, Cherney B, et al: Intraclonal molecular heterogeneity suggests a hierarchy of pathogenetic events in Burkitt’s lymphoma. Ann Oncol 8: 987-994, 1997[Abstract/Free Full Text]

11. Yano T, van Krieken JH, Magrath IT, et al: Histogenetic correlations between subcategories of small noncleaved cell lymphomas. Blood 79: 1282-1290, 1992[Abstract/Free Full Text]

12. Macpherson N, Lesack D, Klasa R, et al: Small, noncleaved (Burkitt-Like) lymphoma: Cytogenetics predict outcome and reflect clinical presentation. J Clin Oncol 17: 1558-1567, 1999[Abstract/Free Full Text]

13. Koduru PR, Raju K, Vadmal V, et al: Correlation between mutation in p53, p53 expression, cytogenetics histologic type and survival in patients with B-cell non-Hodgkin’s lymphoma. Blood 90: 4078-4091, 1997[Abstract/Free Full Text]

14. Sweetenham JW, Pearce R, Taghipour G, et al: Adult Burkitt’s and Burkitt-like Non-Hodgkin’s lymphoma: Outcome for patients treated with high-dose therapy and autologous stem-cell transplantation in first remission or at relapse—Results from the European Group for Blood and Marrow Transplantation. J Clin Oncol 14: 2465-2472, 1996[Abstract]

15. Weintraub M, Adde M, Venzon D, et al: Severe atypical neuropathy associated with administration of hematopoietic colony-stimulating factors and vincristine. J Clin Oncol 14: 935-940, 1996[Abstract/Free Full Text]

16. Rizzieri DA, Johnson JL, Niedzwiecki D, et al: Efficacy and toxicity of brief duration high intensity chemotherapy for small noncleaved cell lymphoma/FAB L3 acute lymphoblastic leukemia: Results of CALGB 9251. Blood 96: 829a, 2000 (suppl, abstr)

Submitted March 6, 2000; accepted June 6, 2001.

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This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, E. J. Articles by Peterson, B. A. Search for Related Content PubMed PubMed Citation Articles by Lee, E. J. Articles by Peterson, B. A.