Originally published as JCO Early Release 10.1200/JCO.2007.11.5477 on December 3 2007

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Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Relapsed, Refractory, and Transformed Indolent Non-Hodgkin's Lymphoma

Andrew R. Rezvani, Barry Storer, Michael Maris, Mohamed L. Sorror, Edward Agura, Richard T. Maziarz, James C. Wade, Thomas Chauncey, Stephen J. Forman, Thoralf Lange, Judith Shizuru, Amelia Langston, Michael A. Pulsipher, Brenda M. Sandmaier, Rainer Storb, David G. Maloney

From the Fred Hutchinson Cancer Research Center; University of Washington; Veterans Affairs Puget Sound Health System, Seattle, WA; Rocky Mountain Cancer Center, Denver, CO; Baylor University, Dallas, TX; Oregon Health and Science University, Portland, OR; Medical College of Wisconsin, Milwaukee, WI; City of Hope National Medical Center, Duarte; Stanford University, Stanford, CA; Emory University, Atlanta, GA; University of Utah, Salt Lake City, UT; and University of Leipzig, Leipzig, Germany

Corresponding author: David G. Maloney, MD, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, MS D1-100, Seattle, WA 98109; e-mail: dmaloney{at}fhcrc.org

	ABSTRACT

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Purpose Few effective treatment options exist for chemotherapy-refractory indolent or transformed non-Hodgkin's lymphoma (NHL). We examined the outcome of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in this setting.

Patients and Methods Sixty-two patients with indolent or transformed NHL were treated with allogeneic HCT from related (n = 34) or unrelated (n = 28) donors after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Nine unrelated donors were mismatched for one HLA antigen. Sixteen patients had histologic transformation before HCT. Twenty patients (32%) had progressive disease after previous high-dose therapy with autologous HCT. Median age was 54 years, and patients had received a median of six lines of treatment before HCT. Median follow-up time after HCT was 36.6 months.

Results At 3 years, the estimated overall survival (OS) and progression-free survival (PFS) rates were 52% and 43%, respectively, for patients with indolent disease, and 18% and 21%, respectively, for patients with transformed disease. Patients with indolent disease and related donors (n = 26) had 3-year estimated OS and PFS rates of 67% and 54%, respectively. The incidences of grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 and 4 acute GVHD, and extensive chronic GVHD were 63%, 18%, and 47%, respectively. Among survivors, the median Karnofsky performance status at last follow-up was 85%.

Conclusion Nonmyeloablative allogeneic HCT can produce durable disease-free survival in patients with relapsed or refractory indolent NHL, even in this relatively elderly and heavily pretreated cohort. Outcomes were particularly good in patients with untransformed disease and related donors, whereas patients with transformed disease did poorly. Long-term survivors reported good overall functional status.

	INTRODUCTION

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Indolent non-Hodgkin's lymphoma (NHL) is considered incurable with current chemotherapeutic approaches. The disease course is characterized by progressively briefer responses to treatment, with death ultimately resulting from refractory disease, transformation to a more aggressive histology, or complications of treatment.

Allogeneic hematopoietic cell transplantation (HCT) can produce a graft-versus-lymphoma (GVL) effect, resulting in disease regression even in chemotherapy-refractory patients. Trials of myeloablative HCT have been characterized by transplantation-related mortality rates of 25% to 40% and have generally been restricted to younger patients and those with an HLA-identical sibling donor.^1-5 However, the median age at diagnosis for the most common types of indolent NHL ranges from 58 to 65 years,⁶ and patients may be significantly older by the time they become refractory to available conventional treatments. Thus, many patients with refractory indolent NHL are ineligible for myeloablative allogeneic HCT.

The development of nonmyeloablative conditioning regimens for allogeneic HCT has allowed expansion of HCT to patients who may be medically unfit for myeloablative HCT. Several studies have examined the role of nonmyeloablative HCT in indolent NHL.^7-13 Here, we report a multicenter experience using nonmyeloablative HCT in patients with refractory, relapsed, or transformed indolent NHL.

	PATIENTS AND METHODS

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Eligibility Criteria
This analysis included data from all patients diagnosed with relapsed, refractory, or transformed indolent NHL who underwent allogeneic HCT after nonmyeloablative conditioning on Fred Hutchinson Cancer Research Center (FHCRC; Seattle, WA) multi-institutional protocols between December 16, 1998 and February 6, 2006.

Patients were treated at 10 centers, with the FHCRC acting as the coordinating center (Appendix Table A1, online only). Protocols were approved by the institutional review boards of the FHCRC and collaborating centers. All patients signed informed consent forms approved by the local institutional review boards.

Inclusion criteria included a diagnosis of indolent NHL,¹⁴ including follicular lymphoma grade IIIA or aggressive NHL histologically demonstrated to have arisen from a pre-existing indolent NHL. Patients with a diagnosis of mantle cell lymphoma were excluded, as were those with lymphoplasmacytic lymphoma and associated Waldenström's macroglobulinemia. Other inclusion criteria included age 50 years or age less than 50 years but at high risk of nonrelapse mortality (NRM) as a result of prior treatment or other comorbidities, and relapse after one or more first-line therapies.

Exclusion criteria were pregnancy, cardiac ejection fraction of less than 40%, pulmonary diffusion capacity less than 35% of predicted value, decompensated liver disease (fulminant hepatic failure or hepatic cirrhosis with portal hypertension), Karnofsky performance status less than 60%, or serologic evidence of infection with HIV. No exclusions were made for disease status, chemotherapy sensitivity, renal insufficiency, or active bacterial or fungal infection.

Pretransplantation Characteristics
Chemotherapy-sensitive disease was defined by the achievement of a partial response (PR) or complete response (CR), according to standard criteria,¹⁵ with the chemotherapy regimen immediately preceding HCT. Pretransplantation comorbidities were assessed retrospectively using the HCT comorbidity index (HCT-CI; Appendix Table A2, online only).^16,17

HLA Typing and Matching
Patients and their donors were tested for HLA-A, HLA-B, and HLA-C by at least intermediate-resolution DNA typing and for HLA-DRB1 and HLA-DQB1 by high-resolution techniques.¹⁸

Conditioning Regimen and Postgrafting Immunosuppression
Patients were initially conditioned with 2 Gy of total-body irradiation at a rate of 0.07 Gy/min from linear accelerators or opposing 60-cobalt sources on day 0. Because of a significant rate of graft rejection in other patient cohorts, fludarabine was subsequently added at a dose of 30 mg/m²/d on days –4 through –2 before HCT. Postgrafting immunosuppression included cyclosporine (or tacrolimus) and mycophenolate mofetil (MMF), as described previously.^19-21 Initially, all patients received MMF 15 mg/kg orally every 12 hours; subsequently, the protocols were altered such that recipients of unrelated-donor allografts were administered MMF 15 mg/kg every 8 hours through day +28 to reduce the risks of graft-versus-host disease (GVHD) and graft rejection.

Post-HCT Monitoring
Patients underwent bone marrow aspiration on days +28, +56, and +84 after HCT to assess chimerism. Unilateral bone marrow biopsy was obtained on day +84 to assess for lymphoma. Patients underwent computed tomography scans of the chest, abdomen, and pelvis on day +56 after HCT (if abnormal before transplantation); on day +84; at 6, 12, 18, and 24 months after HCT; and annually thereafter through 5 years after HCT. Responses were assessed according to standard criteria.¹⁵

Toxicities occurring within the first 100 days after HCT were scored according to the National Cancer Institute Common Toxicity Criteria. GVHD was scored and treated as previously described.^22,23 Any death occurring after HCT in the absence of documented disease progression was considered NRM.

Long-Term Follow-Up
Performance status assessments using the Karnofsky scale were obtained from patients themselves (via questionnaire) or from the patient's primary oncologist. The date on which surviving patients discontinued all immunosuppression was obtained through chart review and contact with participating centers.

Statistical Analysis
Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cumulative incidences were estimated for relapse and NRM. Progression and NRM were the components of PFS and were treated as competing events. Patients with progressive disease after HCT were categorized as relapsed for purposes of PFS, even if they subsequently became disease free in response to postrelapse treatment. Risk factors for survival, relapse/progression, achievement of CR, and NRM were evaluated using Cox regression. All P values are derived from these regression models and are two-sided.

Patient Characteristics
Sixty-two patients at 10 centers underwent HCT from related (n = 34) or unrelated (n = 28) donors (Table 1). Eleven patients received grafts from HLA-mismatched unrelated donors; nine of these mismatches were at the one-antigen level or greater. Among recipients of related allografts, one patient had a one-antigen mismatch; the remainder were HLA-identical. Median follow-up time of surviving patients was 36.6 months (range, 2.3 to 60 months).

Twenty-seven patients (44%) had undergone prior high-dose therapy with autologous HCT; of these, 20 experienced progression after autologous HCT, and seven underwent planned autologous HCT as part of a tandem autologous/allogeneic transplantation protocol for high-risk disease, as defined by the attending physician. One patient had received a nonmyeloablative allogeneic HCT at an outside institution 19 months before HCT but had rejected that graft with autologous reconstitution.

Transplantation Details
All patients received granulocyte colony-stimulating factor–mobilized peripheral-blood stem-cell grafts. The median CD34⁺ cell dose was 8.44 x 10⁶ CD34⁺ cells/kg. Postgrafting immunosuppression consisted of cyclosporine or tacrolimus combined with MMF. Supportive care, including antimicrobial and cytomegalovirus prophylaxis, was administered as described previously.¹⁹ Hematopoietic growth factors were administered to the recipient only for persistent neutropenia after day +28 after HCT.

	RESULTS

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Engraftment
The median neutrophil nadir after HCT was 190 cells/µL (range, 0 to 2,270 cells/µL), with a mean duration of neutropenia (absolute neutrophil count < 500 cells/µL) of 6 days (range, 0 to 28 days). The neutrophil nadir occurred at a median of 13 days after HCT. All patients initially engrafted. Chimerism analysis at day +28 after HCT showed median peripheral-blood CD3, peripheral-blood CD33, and marrow donor chimerism levels of 85%, 95%, and 95.5%, respectively, in patients with related donors and of 94%, 100%, and 100%, respectively, in patients with unrelated donors.

Data on platelet and packed RBC (PRBC) transfusions were available for 53 of 62 patients; of these, 14 (26%) of 53 required platelet transfusion. In patients requiring platelet transfusion, the median number of days with a platelet count of less than 20,000/µL was 3 days (range, 0 to 23 days). Forty (75%) of 53 patients required PRBC transfusion, and the median number of PRBC units administered in patients requiring transfusion was six units (range, two to 33 units).

Two patients (3.2%) experienced nonfatal graft failure after engraftment. The first patient, who had received an HLA-C antigen-mismatched unrelated graft for follicular lymphoma, experienced graft failure 3 months after HCT and received a second nonmyeloablative allogeneic HCT with sustained engraftment. The second patient, who had received an HLA-matched unrelated graft for transformed lymphoma, developed late graft failure 9 months after HCT and also received a second nonmyeloablative allogeneic HCT with sustained engraftment.

GVHD and Toxicity
All patients were assessable for acute GVHD. The incidences of grades 2, 3, and 4 acute GVHD were 45%, 8%, and 10%, respectively. There was a nonsignificant trend toward a higher incidence of grade 2 to 4 acute GVHD in patients with unrelated donors (hazard ratio [HR] = 1.65; 95% CI, 0.9 to 3.1; P = .12). The MMF dosing schedule did not have a significant effect on incidence or severity of acute GVHD. Extensive chronic GVHD developed in 47% of patients who underwent transplantation.

Data on toxicities were available for 54 of 62 patients (Appendix Fig A1, online only). Grade 4 toxicities were uncommon, consisting primarily of hematologic toxicity (26% of patients).

Disease Response
Of the 16 patients in CR at the time of HCT, two (12.5%) experienced relapse after HCT. Among the 46 patients with measurable disease at the time of HCT, objective disease responses were seen in 27 (59%), including 21 CRs and six PRs. In univariate analysis, the likelihood of achieving a CR was higher in patients with chemotherapy-sensitive disease (HR = 3.81; 95% CI, 1.1 to 14; P = .02).

Disease Progression
The cumulative incidence of disease progression at 3 years after HCT was 20%. The incidence was significantly higher in patients with transformed versus indolent disease (38% v 14%, respectively; HR = 4.85; 95% CI, 1.5 to 15.0; P = .001; Fig 1C). In patients with relapse after HCT, the median time from HCT to progression was 7.9 months in patients with indolent disease and 1.6 months in patients with transformed disease.

View larger version (17K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1. (A) Overall and (B) progression-free survival stratified by disease transformation. (C) Relapse rate stratified by disease transformation. (D) Overall and progression-free survival in patients with indolent disease and related grafts (n = 26). The patient with the longest follow-up time died 80.9 months after hematopoietic cell transplantation, during surgery for cardiac valvular disease; she was in complete remission at the time.

Donor Lymphocyte Infusion
Six patients received donor lymphocyte infusion (DLI) after HCT (Table 2). Four patients received DLI for low donor chimerism; all responded with improved chimerism. Two patients received DLI for relapsed or progressive disease; one patient with small lymphocytic lymphoma received chemotherapy and two DLIs for relapse but died of progressive disease without developing GVHD. Another patient received rituximab and DLI for relapsed follicular lymphoma; he had a CR and remains disease free at last follow-up, 24 months after DLI. A third patient with progression of follicular large-cell lymphoma 4 months after HCT had immunosuppression withdrawn to stimulate a GVL effect and developed a CR without DLI; this patient remains alive and disease free at last follow-up, 55 months after HCT.

The majority of NRM was caused by infection, GVHD, or a combination of the two (Table 3). However, seven (27%) of 26 nonrelapse deaths were a result of nontransplantation-related causes (cardiovascular disease, pre-existing leukoencephalopathy, hemorrhage, or second malignancy).

View larger version (12K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2. (A) Overall survival and (B) nonrelapse mortality stratified by donor type. The unrelated group includes patients with HLA-matched or one allele–mismatched unrelated donors (n = 19), whereas the mismatched (MM) unrelated group contains patients mismatched at the one-antigen level or greater (n = 9).

The risk of relapse was increased in patients with transformed (HR = 4.85; 95% CI, 1.5 to 15; P = .001) or chemotherapy-refractory disease (HR = 5.37; 95% CI, 1.7 to 17; P = .005); however, chemotherapy sensitivity did not have a significant impact on OS or PFS. Patients receiving a tandem autologous HCT immediately before allogeneic HCT were also at increased risk of relapse after HCT (HR = 5.47; 95% CI, 1.5 to 21; P = .01); however, such patients were selected for tandem transplantation by virtue of clinically aggressive disease. Factors that did not exert a significant influence on survival, NRM, or relapse in univariate analysis included number of lines of chemotherapy before HCT and treatment with local radiotherapy before HCT (Appendix Table A3, online only).

Long-Term Functional Outcomes
Data on functional status at last follow-up were available for 25 of 28 surviving patients, at a median of 37.1 months after HCT. The median Karnofsky performance status was 85% (range, 60% to 90%; Appendix Fig A2, online only). Ten of the 28 survivors had discontinued all immunosuppression at the time of last follow-up, nine because of resolution of chronic GVHD and one because of disease relapse. Of the nine patients with resolution of chronic GVHD, the median time from HCT to discontinuation of all immunosuppression was 13.1 months (range, 3.2 to 45.3 months).

	DISCUSSION

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Effective treatments are needed for patients with indolent NHL who have become refractory to conventional chemotherapeutic approaches. Prior studies of nonmyeloablative allogeneic HCT for indolent NHL have reported 2-year disease-free survival rates ranging from 54% to 84% and NRM rates ranging from 10% to 30.9%.^9-12 The use of alemtuzumab in the conditioning regimen was associated with a low rate of NRM (11%) but a relatively high rate of relapse (44%).¹⁰ Variations in patient characteristics and conditioning regimens make direct comparisons between these studies difficult.

In comparison with these cohorts, the currently reported group was older (median age, 54 years, v 51,⁹ 42,¹¹ 48,¹⁰ and 48 years¹²) and more heavily pretreated (median number of prior lines of chemotherapy, six lines, v two,⁹ three,¹¹ three,¹⁰ and four lines¹²). We report a relatively high rate of NRM compared with these prior cohorts. Possible explanations include the advanced age and heavy pretreatment of this group of patients, as well as the prevalence of comorbidities as quantified by the HCT-CI. In addition, we found recipients of HLA-mismatched unrelated allografts to be at particularly high risk of NRM; no such patients were included in the cohorts reported by others.

Patients with transformed disease suffered a high rate of relapse, perhaps indicating that insufficient time was available with such aggressive disease for a GVL effect to become evident. We included only patients with histologically confirmed transformation in the analysis; because most patients were not biopsied immediately before HCT, it is possible that some patients with undocumented transformation were categorized as indolent.

We observed plateaus in both PFS and OS by approximately 2 years, suggesting that a significant number of patients achieve durable long-term disease stabilization or remission as a result of GVL effects. Immune manipulations, including DLI and withdrawal of immunosuppression, were effective in the small number of patients in which they were used, confirming the importance of the immunologic GVL effect.

The potential long-term complications of HCT, including chronic GVHD, may lead to questions regarding the quality of life and functional outcomes of disease-free survivors. In this cohort, surviving patients reported good performance status. A significant proportion of patients were able to discontinue immunosuppression in response to resolution of chronic GVHD, and only a small minority had disabling chronic GVHD. These results, although only indirectly reflecting quality of life, suggest that most survivors of nonmyeloablative HCT are not disabled by complications of the transplantation and have returned to a reasonable level of activity.

Differences between this cohort and others studied make direct comparisons difficult, but a body of evidence is emerging that suggests that nonmyeloablative allogeneic HCT is an effective treatment for patients with refractory indolent NHL, with the potential to effect long-term disease-free survival with acceptable functional status. However, several important questions remain unanswered. The ideal timing of HCT is unclear; if disease transformation occurs before HCT, outcomes are poor, but given the significant upfront morbidity and mortality associated with even nonmyeloablative HCT, a strategy of early HCT may not be an ideal solution. The HCT-CI score may be a useful tool to aid in the selection of patients with indolent NHL for nonmyeloablative allogeneic HCT because higher scores correlated with an elevated risk of NRM. Finally, given the relatively high rate of NRM in this cohort, much of it a result of GVHD and infection, continued improvements in the prevention and treatment of GVHD and in supportive care are needed.

On the basis of these findings, we pursue an individualized approach to the timing of nonmyeloablative allogeneic HCT in patients with indolent lymphoma based on factors such as patient goals and preferences, prognosis of the disease with conventional therapy, patient comorbidities, and donor availability.

In conclusion, our findings add to a growing body of evidence indicating that nonmyeloablative allogeneic HCT can provide effective immunologic control and long-term disease-free survival in patients with relapsed or refractory indolent NHL, with generally good functional outcomes. Further study aimed at defining the optimal timing of allogeneic HCT and reducing NRM in this often elderly, heavily pretreated, and comorbidity-rich population is needed. Ultimately, strategies that specifically augment the graft-versus-tumor reaction while avoiding GVHD may further decrease NRM and improve disease control.

	AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment: N/A Leadership: N/A Consultant: N/A Stock: N/A Honoraria: Edward Agura, Genzyme Research Funds: N/A Testimony: N/A Other: N/A

	AUTHOR CONTRIBUTIONS

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Conception and design: Andrew R. Rezvani, Michael Maris, Michael A. Pulsipher, Brenda M. Sandmaier, Rainer Storb, David G. Maloney

Financial support: Rainer Storb

Provision of study materials or patients: Michael Maris, Edward Agura, Richard T. Maziarz, James C. Wade, Thomas Chauncey, Thoralf Lange, Judith Shizuru, Amelia Langston, Michael A. Pulsipher, Brenda M. Sandmaier

Collection and assembly of data: Andrew R. Rezvani, Barry Storer, Michael Maris, Mohamed L. Sorror, Thoralf Lange, Judith Shizuru, Amelia Langston, Brenda M. Sandmaier

Data analysis and interpretation: Andrew R. Rezvani, Barry Storer, Michael Maris, Mohamed L. Sorror, Richard T. Maziarz, Amelia Langston, Brenda M. Sandmaier, Rainer Storb, David G. Maloney

Manuscript writing: Andrew R. Rezvani, Barry Storer, Edward Agura, Michael A. Pulsipher, Brenda M. Sandmaier, Rainer Storb, David G. Maloney

Final approval of manuscript: Andrew R. Rezvani, Barry Storer, Michael Maris, Mohamed L. Sorror, Edward Agura, Richard T. Maziarz, James C. Wade, Thomas Chauncey, Stephen J. Forman, Judith Shizuru, Michael A. Pulsipher, Brenda M. Sandmaier, Rainer Storb, David G. Maloney

	Appendix

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 

View larger version (12K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig A1. Grade 3 and 4 toxicities by system (first 100 days after hematopoietic cell transplantation), according to the National Cancer Institute Common Toxicity Criteria.

View larger version (8K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig A2. Karnofsky performance status of surviving patients (n = 25).

	ACKNOWLEDGMENTS

 
We thank Jennifer Freese, Heather Hildebrant, and Courtney McNamara for assistance with data retrieval, and Bonnie Larson and Helen Crawford for assistance with manuscript preparation. We also thank the patients who participated in these protocols and the nurses and staff who cared for them.

	NOTES

 
published online ahead of print at www.jco.org on December 3, 2007.

Supported by Grants No. CA78902, CA18029, CA15704, and K99-HL088021 from the National Institutes of Health, Bethesda, MD.

Presented in part as a poster at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION AUTHORS' DISCLOSURES OF... AUTHOR CONTRIBUTIONS Appendix REFERENCES

 
1. Toze CL, Barnett MJ, Connors JM, et al: Long-term disease-free survival of patients with advanced follicular lymphoma after allogeneic bone marrow transplantation. Br J Haematol 127:311-321, 2004[CrossRef][Medline]

2. Yakoub-Agha I, Fawaz A, Folliot O, et al: Allogeneic bone marrow transplantation in patients with follicular lymphoma: A single center study. Bone Marrow Transplant 30:229-234, 2002[CrossRef][Medline]

3. van Besien K, Loberiza FRJ, Bajorunaite R, et al: Comparison of autologous and allogeneic hematopoietic stem cell transplantation for follicular lymphoma. Blood 102:3521-3529, 2003[Abstract/Free Full Text]

4. Verdonck LF, Dekker AW, Lokhorst HM, et al: Allogeneic versus autologous bone marrow transplantation for refractory and recurrent low-grade non-Hodgkin's lymphoma. Blood 90:4201-4205, 1997[Abstract/Free Full Text]

5. van Besien K, Sobocinski KA, Rowlings PA, et al: Allogeneic bone marrow transplantation for low-grade lymphoma. Blood 92:1832-1836, 1998[Abstract/Free Full Text]

6. The Non-Hodgkin's Lymphoma Classification Project: A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood 89:3909-3918, 1997[Abstract/Free Full Text]

7. Escalon MP, Champlin RE, Saliba RM, et al: Nonmyeloablative allogeneic hematopoietic transplantation: A promising salvage therapy for patients with non-Hodgkin's lymphoma whose disease has failed a prior autologous transplantation. J Clin Oncol 22:2419-2423, 2004[Abstract/Free Full Text]

8. Khouri IF, Keating M, Körbling M, et al: Transplant-lite: Induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 16:2817-2824, 1998[Abstract]

9. Khouri IF, Saliba RM, Giralt SA, et al: Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: Low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood 98:3595-3599, 2001[Abstract/Free Full Text]

10. Morris E, Thomson K, Craddock C, et al: Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood 104:3865-3871, 2004[Abstract/Free Full Text]

11. Robinson SP, Goldstone AH, Mackinnon S, et al: Chemoresistant or aggressive lymphoma predicts for a poor outcome following reduced-intensity allogeneic progenitor cell transplantation: An analysis from the Lymphoma Working Party of the European Group for Blood and Bone Marrow Transplantation. Blood 100:4310-4316, 2002[Abstract/Free Full Text]

12. Kusumi E, Kami M, Kanda Y, et al: Reduced-intensity hematopoietic stem-cell transplantation for malignant lymphoma: A retrospective survey of 112 adult patients in Japan. Bone Marrow Transplant 36:205-213, 2005[Medline]

13. Rodriguez R, Nademanee A, Ruel N, et al: Comparison of reduced-intensity and conventional myeloablative regimens for allogeneic transplantation in non-Hodgkin's lymphoma. Biol Blood Marrow Transplant 12:1326-1334, 2006[CrossRef][Medline]

14. World Health Organization.World Health Organization Classification of Tumours. Pathology and Genetics: Tumours of Hematopoietic and Lymphoid Tissues. Washington, DC, International Agency for Research on Cancer Press, 2001

15. Cheson BD, Horning SJ, Coiffier B, et al: Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas: NCI Sponsored International Working Group. J Clin Oncol 17:1244, 1999[Abstract/Free Full Text]

16. Charlson ME, Pompei P, Ales KL, et al: A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis 40:373-383, 1987[CrossRef][Medline]

17. Sorror ML, Maris MB, Storb R, et al: Hematopoietic cell transplantation (HCT)-specific comorbidity index: A new tool for risk assessment before allogeneic HCT. Blood 106:2912-2919, 2005[Abstract/Free Full Text]

18. Petersdorf EW, Gooley TA, Anasetti C, et al: Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood 92:3515-3520, 1998[Abstract/Free Full Text]

19. Maris MB, Niederwieser D, Sandmaier BM, et al: HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood 102:2021-2030, 2003[Abstract/Free Full Text]

20. Maloney DG, Molina AJ, Sahebi F, et al: Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood 102:3447-3454, 2003[Abstract/Free Full Text]

21. Baron F, Maris MB, Storer BE, et al: HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with chronic myeloid leukemia. Biol Blood Marrow Transplant 11:272-279, 2005[CrossRef][Medline]

22. Przepiorka D, Weisdorf D, Martin P, et al: 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant 15:825-828, 1995[Medline]

23. Sullivan KM, Agura E, Anasetti C, et al: Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 28:250-259, 1991[Medline]

Submitted March 8, 2007; accepted October 1, 2007.

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				C. A. Rodrigues, G. Sanz, C. G. Brunstein, J. Sanz, J. E. Wagner, M. Renaud, M. de Lima, M. S. Cairo, S. Furst, B. Rio, et al. Analysis of Risk Factors for Outcomes After Unrelated Cord Blood Transplantation in Adults With Lymphoid Malignancies: A Study by the Eurocord-Netcord and Lymphoma Working Party of the European Group for Blood and Marrow Transplantation J. Clin. Oncol., January 10, 2009; 27(2): 256 - 263. [Abstract] [Full Text] [PDF]

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				B. G. Till, M. C. Jensen, J. Wang, E. Y. Chen, B. L. Wood, H. A. Greisman, X. Qian, S. E. James, A. Raubitschek, S. J. Forman, et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells Blood, September 15, 2008; 112(6): 2261 - 2271. [Abstract] [Full Text] [PDF]

				M. Bendandi Aiming at a Curative Strategy for Follicular Lymphoma CA Cancer J Clin, September 1, 2008; 58(5): 305 - 317. [Abstract] [Full Text] [PDF]

				Allogeneic Stem-Cell Transplantation for Indolent Lymphoma Journal Watch Oncology and Hematology, March 4, 2008; 2008(304): 2 - 2. [Full Text]

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