Bone Marrow Transplantation (2003) 31, 441–446 & 2003 Nature Publishing Group All rights reserved 0268-3369/03 $25.00 www.nature.com/bmt Non-Hodgkins lymphoma High-dose cyclophosphamide, BCNU, and VP-16 (CBV) conditioning before allogeneic stem cell transplantation for patients with non-Hodgkin’s lymphoma

HA Rossi, PS Becker, RVB Emmons, P Westervelt, W Levy1, Q Liu2, Y Clark andK Ballen 3

Division of Hematology and Oncology, Umass Memorial Healthcare, North Worcester, MA, USA

Summary: rates are lower in patients treatedwith allogeneic SCT, especially for those with chronic GVHD, comparedwith Allogeneic stem cell transplantation (SCT) has been autotransplant patients; this observation suggests a graft- shown to be a curative therapy for some patients with versus-lymphoma effect.4 Preperative regimens for patients non-Hodgkin’s lymphoma (NHL). Total-body irradiation with non-Hodgkin’s lymphoma (NHL) undergoing allo- and high-dose cyclophosphamide combinations are the geneic SCT frequently include cytoxan plus total-body most established conditioning regimens used in this irradiation (TBI).5,6 However, it is unclear whether this setting. We examined the efficacy and toxicity of regimen has optimal antilymphoma activity; recurrences of cyclophosphamide, BCNU, and VP-16 (CBV) as a 20–60% are reported depending upon histologic subtypes, suitable chemotherapy-only regimen for NHL patients. prior therapies, andtumor chemosensitivity. 1,5,7 Further- In total, 18 patients, median age 42 years, with NHL were more, TBI is associatedwith interstitial pneumonitis (IP) treated with CBV followed by allotransplant. Patients had and patients with prior mediastinal radiation therapy may received a median of two prior chemotherapy regimens. not be eligible for TBI; the total-radiation dose is one of the Median times to neutrophil and platelet recovery were 19 most significant risk factors for transplant-relateddeath. 8 and 15 days, respectively. Interstitial pneumonitis oc- Long-term complications of TBI are also concerning and curred in one patient. There have been four relapses after include myelodysplasia, acute leukemia, cataracts, and a median follow-up of 39 months. Overall, there were four endocrine insufficiencies.9,10 deaths, one because of relapse. The 2-year estimates of The combination of high-dose cytoxan, carmustine, and relapse-free and overall survival are 56 and 76%, etoposide (CBV) has been used extensively as a non-TBI- respectively. CBV is a safe and an effective alternative containing regimen for patients receiving autologous SCT to TBI-containing regimens before allogeneic SCT for for lymphoma.11–13 In comparison, the experience with NHL. CBV for allogeneic transplants is described mostly in Bone Marrow Transplantation (2003) 31, 441–446. series of patients with a history of prior dose-limiting doi:10.1038/sj.bmt.1703874 radiotherapy or included among patients treated with Keywords: non-Hodgkin lymphoma; stem cell transplan- various conditioning regimens.14–16 Our report is unique tation; allogeneic; conditioning therapy; carmustine in its combination of patients mostly without prior radiation, the exclusion of Hodgkin disease patients, and the carmustine dosing of 450 mg/m2 rather than the more toxic 600 mg/m2. Allogeneic hematopoietic stem cell transplantation (SCT) is usedless frequently than autologous SCT in the treatment of lymphoma. Benefits of allogeneic SCT are limitedby high regimen-relatedtoxicity, especially graft-versus-host Patients and methods disease (GVHD).1,2 However, allogeneic SCT may be preferable for younger patients with chemoresistant dis- All patients anddonorsgave written informedconsent as ease, dense marrow infiltration, severe hypocellularity, or approvedby the Institutional Review Boardof University some high-grade lymphomas.1,3 Relapse andprogression of Massachusetts Medical School. All patients were age 18– 55 years with creatinine clearance greater than 70 ml/min, left ventricular ejection fraction greater than 50%, liver transaminases andbilirubin no more than 1.5 times normal, Correspondence: Dr HA Rossi, Division of Hematology and Oncology, Umass Memorial Healthcare, 55 Lake Avenue North, Worcester, MA andnormal pulmonary function tests. 01655, USA 1Current Address: Fred Hutchinson Cancer Research Center, Seattle, USA. Treatment regimen 2Cancer Center, Umass Medical School, Worcester MA, USA. 3Massachusetts General Hospital, Boston, MA, USA. High-dose chemotherapy was administered on transplant Received7 March 2002; accepted15 October 2002 days –6 to –3 and included cyclophosphamide 750 mg/m2 CBV with allotransplant for NHL HA Rossi et al 442 every 12 h for 4 days (total dose 6 gm/m2), carmustine Results 112.5 mg/m2 per day for 4 days (total dose 450 mg/m2), and etoposide 200 mg/m2 every 12 h for 4 days (total dose Patient characteristics 1600 mg/m2). No chemotherapy was given on days –2 and Between November 1996 andApril 2002, 18 patients with –1. Stem cells from a 6/6 HLA-matchedsibling were NHL were treatedwith CBV followedby bone marrow or infusedon day0. The first five patients receivedallogeneic peripheral bloodstem cells from HLA-identical sibling bone marrow andthe remaining 13 patients received donors. Pretransplant characteristics for each patient are allogeneic peripheral bloodstem cells. One patient received shown in Table 1. There were 14 men andfour women with a combination of marrow and peripheral blood-derived a median age of 42 years (range, 20–50). Disease histology stem cells. Post-transplant immunosuppression was included diffuse large B cell (2), high-grade B cell (4), achieved using daily cyclosporine beginning day –1 and follicular B cell (4), T cell (3), mantle cell (2), small methotrexate 15 mg/m2 on day +1 followed by methotrex- lymphocytic/CLL (2), andmucosa-associatedlymphoid ate 10 mg/m2 on days +3, +6, and +11. Cyclosporine was tissue (MALT) (1) lymphomas. Patients hadreceiveda taperedbetween days100 and180. All patients received median of two chemotherapy regimens prior to transplant prophylactic antibacterial drugs, acyclovir, bactrim, and conditioning. One patient (no. 7) had previously received an low-dose amphotericin according to the policies of autotransplant andone patient (no. 6) hadpreviously the Umass Memorial Health Care Stem Cell receiveda T-cell-depletedallogeneic SCT. Three patients Transplant program. Growth factors were not routinely hadreceivedprior irradiation to the mediastinum (no. 4), administered. Patients were hospitalized in isolation rooms total body (no. 6), or neck (no. 15). Five patients had less with laminar air flow andthe transplant unit was HEPA than a partial response to their last chemotherapy regimen. filtered. Among the patients who were transplantedafter first-line therapy, one hadrefractory lymphoma, three hadfailedto Evaluation of response and engraftment achieve CR, andthree were in first CR. First CR patients hadhigh-gradelymphomas andwere consideredappropriate Tumor staging studies including appropriate imaging were for allogeneic transplant because of intolerance to repeat performed100 days,12 months, and24 months after cycles of intensive ALL-type regimen (no. 3), bulky disease transplant. Bone marrow aspirate andbiopsy were and first-line therapy with cyclophosphamide, adriamycin, performed100 days,6 months, and12 months after vincristine, andprednisone (CHOP) only (no. 5), andthe transplant. Responses to previous chemotherapy andto presence at diagnosis of three international prognostic index the transplant regimen were defined according to standard (IPI) risk factors (no. 14). Five patients hadbone marrow criteria.17 Neutrophil count recovery was defined as the first involvedwith lymphoma at the time of transplant. of 3 consecutive days when the absolute neutrophil count exceeded 0.5 Â 109/l bloodandplatelet count recovery was defined as the day when the platelet count exceeded Neutrophil and platelet recovery 20 Â 109/l blood independent of platelet transfusion. Times to cell count recovery were reportedfrom the dateof All patients hadrecovery of neutrophil numbers, andthe transplant. median time to a neutrophil count greater than 0.5 Â 109/l

Table 1 Pre-transplant patient characteristics

Patient Age Sex Tumor Marrow Prior Disease Prior CR Stage Prior Outcome class disease regimen duration response 1 36 f Burkitt No 1 6 months No 3 Sensitive CR 2 30 f MCL No 1 10 months No 4 Resistant R 3 28 m PBLL No 1 5 months Yes cr Sensitive CR 4 42 m FCC I Yes 5 3.5 years No 4 Resistant TRD 5 40 m Burkitt No 1 10 months Yes cr Sensitive CR 6 47 m CLL/SLL Yes 2 7 years Yes rai 3 Sensitive CR 7 41 m DLCL No 4 7 years Yes 3 Resistant TRD 8 31 m Burkitt-like No 1 5 months No 3 Sensitive CR 9 33 m FCC III No 2 6 months No 3 Resistant R 10 50 m FCC III No 2 5 years Yes 3 Sensitive TRD 11 20 m PTCL No 2 1 years Yes 2 Sensitive R 12 43 m MCL Yes 2 3 years Yes 4 Sensitive CR 13 41 m CLL/SLL Yes 1 10 months No rai 1 Sensitive CR 14 43 m Burkitt No 1 4 months Yes cr Sensitive CR 15 49 m ALCL No 3 14 months Yes cr Sensitive R 16 43 m FCC II Yes 2 8 months No 4 Sensitive CR 17 24 f MALT No 4 14 months No 2E Sensitive RD 18 31 f DLCL No 2 6 months No 3 Resistant CR

Abbreviations: MCL, mantle cell lymphoma; PBLL, precursor B lymphoblastic lymphoma; FCC I, follicle center cell grade I; CLL/ SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; DLCL, diffuse large B-cell lymphoma; PTCL, peripheral T-cell lymphoma; ALCL, anaplastic large T-cell lymphoma; MALT, mucosa-associatedlymphoidtissue; CR, complete response; R, relapse; TRD, treatment-relateddeath

Bone Marrow Transplantation CBV with allotransplant for NHL HA Rossi et al 443 was 19 days (range, 14–29 days). There was a trend toward 1.00 faster neutrophil recovery time after peripheral stem cell infusion than after bone marrow infusion (17 vs 24.5 days, NS). No life-threatening infections occurredduringneu- 0.75 tropenia. In all, 15 patients achieveda self-sustained 9 platelet count above 20 Â 10 /l at a median of 17 days 0.50 (range, 7–43 days) Three patients died before platelet recovery; however, there were no deaths due primarily to hemorrhage. No association was notedbetween cell count 0.25

recovery anddiseasehistology or number of prior Probability of survival therapies. No patient was diagnosed with graft rejection. One patient developed severe thrombocytopenia associated 0.00 with exposure to chemical solvents 10 months after 0 200 400 600 800 1000 12001400 1600 18002000 transplant andsubsequently recoveredfully. Days after transplant

Figure 2 Relapse-free survival after allogeneic stem cell transplantation. Relapse and survival

Five patients have hadrelapse of lymphoma. Patients 2 and Table 2 Adverse outcomes 15 hadlocalizednodalrelapse at 35 months and9 months, respectively, post-transplant. Both receiveddonorlympho- Adverse outcomes No. (%) cyte infusion (DLI) as treatment for their lymphoma Graft failure 0 relapse. Both developed GVHD and are without evidence Acute GVHD 4 (17) of lymphoma 3 years and9 months, respectively, after DLI. Chronic GVHD 5 (22) VOD 3 (17) Patients 9 and11 hadprogressive chest adenopathyat 4 Interstitial pneumonitis 1 (6) months post-transplant. Both patients were treatedwith Relapse 4 (23) local irradiation and achieved resolution of adenopathy. Cause of death Interestingly, they both subsequently developed chronic Lymphoma 1 (6) Interstitial pneumonitis 1 (6) GVHD andhave hadno evidenceof lymphoma for the Infection 2 (11) subsequent 26 and17 months, respectively. Patient 17 had Total deaths 4 (23) relapsedor persistent MALT lymphoma diagnosed2 100-day mortality 1 (6) months after transplant andlymphoma was the cause of death. There have been no relapses among high-grade lymphoma patients. No relapses have occurredamong patients with GVHD. GVHD and nonrelapse mortality Surviving patients have been followedfor a medianof 43 months (range, 7–61 months). The Kaplan–Meier estimates Clinical outcomes are presentedin Tables 1 and2. Grade2 of relapse-free andoverall survival after CBV/allogeneic or 3 acute GVHD was diagnosed in four patients; the liver transplantation are shown in Figures 1 and2. The 2-year was involvedin all four cases andskin was involvedin three actuarial estimates of relapse-free andoverall survival are cases. Extensive chronic GVHD occurredin four patients; 56 and76%, respectively. The mediansurvival for this all four cases were responsive to immunosuppressive patient group has not yet been reached. agents andsteroids.However, two of these patients developed persistent leukopenia and died of infectious complications. There was a total of four deaths; three deaths noted above were attributedto complications of therapy. Non- relapse deaths occurred in patients with multiple prior Kaplan-Meier survival estimate 1.00 chemotherapy regimens and long durations of disease. One patient (no. 17) died of relapsed lymphoma. The 100 day andoverall nonrelapse mortality were 6 and17% , 0.75 respectively.

0.50 Pulmonary, hepatic toxicity, and infections There was one case of regimen-relatedIP that developedon 0.25

Probability of survival day 17. One patient was diagnosed with pulmonary fibrosis 6 months after transplant; this patient was also foundto 0.00 have severe nonischemic dilated cardiomyopathy. Three patients with a history of prior radiation therapy did not 0 200 400 600 800 100012001400160018002000 experience significant pulmonary toxicity. Three patients Overall survival time (days) were diagnosed with mild veno-occlusive disease of the Figure 1 Overall survival after allogeneic stem cell transplantation. liver; serum bilirubin remainedless than 4 g/dlin all cases.

Bone Marrow Transplantation CBV with allotransplant for NHL HA Rossi et al 444 One patient developed a mild chronic hepatitis of unknown reportedfollowing autologous SCT. 21,22 Recently, a sig- etiology 7 months after transplant andanother developed nificant benefit from autologous SCT comparedto inter- pancreatitis after 11 months; both of these conditions feron maintenance was reported.23 Furthermore, among a resolvedspontaneously. series of 32 patients treatedwith allogeneic SCT (including Sepsis syndrome developed in three patients. Organisms both TBI andnon-TBI regimens), the 5-year disease-free isolatedfrom the bloodof these patients were Klebsiella, survival rate was 41% andno significant differencein Enterococcus, andPseudomonasspecies. Aspergillus was outcome has been notedbetween myeloablative and isolatedfrom three patients with cGVHD; the outcomes nonmyeloablative regimens.24 were death from aspergillus pneumonia (no. 4) and The patients in our study were offered allogeneic resolution with itraconazole therapy (no. 11). Patient 7 transplantation because of the availability of an identical- died of sepsis/multiorgan failure; aspergilloma was found match sibling donor and young patient age, bone marrow incidentally at autopsy. Neither CMV nor HSV infection involvement, or a history of heavy pretreatment, including was diagnosed in any patient. prior high-dose therapy. It is difficult to evaluate the effect of CBV/allogeneic SCT upon overcoming chemo-resistance in our study; most of our patients had disease sensitive to Discussion their previous chemotherapy courses. Also, three of our more heavily pretreatedpatients diedoftreatment-related Our group of patients with relapsedlymphoma treatedwith complications rather than of relapse. Nevertheless, our CBV andallogeneic SCT experiencedhigh relapse-free and results suggest a graft-versus-lymphoma effect; no patient overall survival with a low early mortality rate. Rates of cell developed a relapse after being diagnosed with GVHD. count recovery were comparable to rates seen after TBI- Furthermore, four of five patients with relapse have had containing regimens. These results suggest that CBV is an disease remission in the setting of GVHD occurring after acceptable alternative to TBI-containing regimens prior to the diagnosis of relapse or persistent disease. allogeneic SCT for patients with or without prior radiation In current practice most patients with chemotherapy- therapy. sensitive relapsedaggressive NHL receive autologous Our study population was heterogeneous and included SCT.25,26 In this setting, long-term relapse-free survivals patients with follicular lymphomas, aggressive lymphomas, of 40–50% andtreatment-relatedmortality of 5–10% have mantle cell lymphoma, andSLL/CLL; this must be been reported.1,9,26–28 However, relapse of lymphoma considered when comparing our findings with those of remains the primary cause of treatment failure after other allogeneic SCT trials. Among the four patients with autologous SCT andmyelodysplasiais not uncommon follicular lymphomas, there have been two relapses andone among surviving patients.29,30 Although there are no transplant-relateddeath,while among nine aggressive available randomized data to show superiority of an diffuse lymphoma patients who were less heavily pre- allogeneic approach in NHL, the advantage of tumor-free treated, there has been one relapse and one transplant- stem cells anda graft-versus-lymphoma effect make this an relateddeath. attractive alternative for young patients with a history of Owing to the long natural history of the follicular heavy pretreatment or refractory lymphoma.3,14,31,32 A lymphomas, the optimal use of SCT for these patients is graft-versus-lymphoma effect may overcome chemotherapy poorly defined. It is clear that patients with advanced resistance andallow long-term survival in a minority of disease are not cured with conventional chemotherapy and, refractory lymphoma patients.33 Unfortunately , improve- therefore, transplant approaches are often sought. Heavy ments in relapse-free survival after allogeneic SCT are pretreatment andthe lack of a cure rate with chemotherapy generally offset by increasedtreatment-relatedmortality. alone often make allogeneic stem cells the preferredsource Therefore, strategies for decreasing toxicity while main- in these cases. Van Besien et al7 reported113 patients taining the engraftment rate andantilymphoma effect treatedwith allogeneic transplantation for low-grade couldimprove outcomes for relapsedor refractory lym- lymphoma; disease-free survival, overall survival, and phoma patients. treatment relatedmortality were 49, 49, and40%, Randomized leukemia trials have shown equivalence respectively, at 3 years. Long-term survival of 25–35% between busulfan plus cytoxan andcytoxan plus TBI. 34,35 has been reportedafter allogeneic SCT for salvage therapy However, in the absence of randomized lymphoma trials, for aggressive lymphomas.1,5,18 the comparative effect of TBI vs non-TBI-containing Published data regarding allogeneic SCT for CLL are regimens is unknown. Uncontrolledstudiesmay be biased limited. Remission rates of 70% and long-term failure-free against chemotherapy-only regimens because they are survival rates of 46–65% have been reported.19,20 Both of offeredto patients with the most resistant diseaserequiring our SLL/CLL patients remain in CR; one of these patients local radiotherapy.33 Nonrandomized comparisons have hadfailedafter a prior T-cell-depletedallotransplant,but generally shown equivalent relapse-free survival andoverall has remainedin CR for 50 months after the allotransplant survival between chemotherapy-only andchemotherapy– performedin this study. TBI regimens 1,36 Williams et al37 reporteda trendtoward One of our two mantle cell lymphoma patients relapsed shorter survival among TBI-treatedautotransplant pa- after 32 months, but remission was subsequently achieved tients. An observational study of 113 low-grade lymphoma after DLI. The management of mantle cell lymphoma is patients receiving allogeneic SCT showedsuperiority of particularly challenging because of frequent resistance to TBI regimens; however, the majority of chemotherapy-only chemotherapy; consequently, high relapse rates are often patients receivedbusulfan plus cytoxan; 7 this combination

Bone Marrow Transplantation CBV with allotransplant for NHL HA Rossi et al 445 may not have optimal antilymphoma activity andthe who are candidates for allogeneic SCT, but who have an relapse rate is high after busulfan/cytoxan.38 TBI is increasedrisk for TBI-relatedtoxicity may benefit from a associatedwith significant pulmonary toxicity, especially chemotherapy-only conditioning regimen. A randomized after previous mediastinal irradiation, and it should not be trial comparing CBV to Cytoxan/TBI may be warranted. used after a history of radiation toxicity or dose-limiting therapy to the chest, liver, or CNS. Non-TBI-containing preparative regimens such as CBV have been usedmost commonly prior to autologous SCT References for Hodgkins and NHL.14,39,40 Although IP remains an important cause of toxic death, toxicity of CBV has been 1 Chopra R, Goldstone AH, Pearce R et al. Autologous versus reduced by using a BCNU dose of 300–450 mg/m2 rather allogeneic bone marrow transplantation for non-Hodgkin’s than 600 mg/m2, andthe substitution of lomustine for lymphoma: a case controlledanalysis of the European Bone BCNU may also reduce pulmonary toxicity.9,39,41 An early Marrow Transplant Group Registry data. J Clin Oncol 1992; study of CBV for allotransplantation reported no signifi- 10: 1690–1695. cant organ toxicity among 29 acute leukemia patients.16 In 2 MilpiedN, FieldingAK, Pearce RM. Allogeneic bone marrow the recently reportedLNH87–2 protocol for poor-risk transplant is not better than autologous transplant for patients with relapsed Hodgkin’s disease. European Group for Blood aggressive NHL, there were no toxic deaths and no cases of andBone Marrow Transplantation. J Clin Oncol 1996; 14: late myelodysplasia among 125 autologous SCT patients 1291–1296. 2,42 receiving CBV with a BCNU dose of 300 mg/m. 3 Ratanatharathorn V, Uberti J, Karanes C et al. Prospective Treatment-relatedtoxicity was relatively low among our comparative trial of autologous versus allogeneic bone marrow study patients. Pulmonary toxicity occurred in two patients transplantation in patients with non-Hodgkin’s lymphoma. (11%) with one death (6%) because of IP. This compares Blood 1994; 84: 1050–1055. favorably with the 10–20% rates of death from pulmonary 4 Copelan EA, Kapoor N, Gibbins B et al. Allogeneic marrow causes reportedin other series of lymphoma patients transplantation in non-Hodgkin’s lymphoma. Bone Marrow receiving allogeneic transplantation.5,7,14 Of note, two of Transplant 1990; 5: 47–50. et al our patients who hadreceivedprior TBI or chest RT did 5 Applebaum FR, Sullivan KM, Buckner CD . Treatment of malignant lymphoma in 100 patients with chemotherapy, total not experience pulmonary toxicity. VOD was infrequent in body irradiation, and marrow transplantation. J Clin Oncol our study and the cases were not life-threatening. The 6% 1987; 5: 1340–1347. observed 100-day mortality of our study compares favor- 6 Petersen, FB, Appelbaum FR, Hill R et al. Autologous ably to other reports of allogeneic SCT for lymphoma3–5. marrow transplantation for malignant lymphoma. A report of Nonrelapse mortality was comparable to the rates seen 101 cases from Seattle. J Clin Oncol 1990; 8: 638–647. after nonmyeloablative transplant.43 These acceptable rates 7 Van Besien K, Sobocinski KA, Rowlings PA et al. Allogeneic of toxicity among our patients couldrelate to the absence bone marrow transplantation for low-grade lymphoma. Blood of TBI conditioning, the dose of BCNU, and/or the low 1998; 92: 1832–1838. percentage of patients with a history of radiation therapy. 8 Clift RA, Buckner CD, Appelbaum FR et al. Allogeneic Times to cell count recovery andthe total durationof marrow transplantation in patients with chronic myeloid leukemia in the chronic phase: a randomized trial of two neutropenia andthrombocytopenia were comparable to irradiation regimens. Blood 1991; 8: 1660–1667. 15,33,44 other reports of allotransplant for lymphoma. This 9 Wheeler C, KhurshidA, Ibrahim J et al. Incidence of post indicates that CBV is sufficiently immunosuppressive to transplant myelodysplasia/acute leukemia in non-Hodgkin’s allow engraftment of donor hematopoietic cells. Other lymphoma patients compared with Hodgkin’s disease patients investigators have shown that CBV permits allogeneic stem undergoing autologous transplantation following cyclopho- cell engraftment in lymphoma patients with prior dose- sphamide, carmustine, and etoposide (CBV). Leuk Lymphoma limiting radiation therapy. In one series of 56 patients 2001; 40: 499–509. treatedwith CBV containing BCNU 600/m 2, neutrophil 10 Kolb HJ, Bender Go¨ tze Ch. Late complications after andplatelet recovery occurredat mediantimes of 20 and22 allogeneic bone marrow transplantation for leukemia. Bone Marrow Transplant days, respectively. However, 11% of patients died without 1990; 6: 61–67. 11 Gribben JG, Linch JG, andSinger CRJ. Successful treatment neutrophil recovery and33% diedwithoutplatelet of refractory Hodgkin’s disease by high-dose combination 14 recovery. Effective engraftment has been reportedafter chemotherapy andautologous bone marrow transplantation. CBV/allogeneic SCT for Hodgkin’s lymphoma; these Blood 1989; 73: 340–344. patients may be more immunosuppressedandless likely 12 Wheeler C, Antin JH, Churchill WH et al. Cyclophosphamide, to exhibit host-versus-graft resistance than patients with carmustine, andetoposidewith autologous bone marrow NHL.15 Additionally, Zander et al16 confirmedthe presence transplantation in refractory Hodgkin’s disease and non- of donor hematopoiesis in all but one of 29 leukemia Hodgkin’s lymphoma: a dose-finding study. J Clin Oncol patients treatedwith CBV. 1990; 8: 648–656. In summary, high-dose CBV chemotherapy permits 13 Gulati SC, Shank B, Black P et al. Autologous bone marrow J engraftment of HLA-matchedsibling donorhematopoietic transplantation for patients with poor-prognosis lymphoma. Clin Oncol 1988; 6: 1303–1313. stem cells. Treatment of NHL patients with this regimen is 14 Demirer T, Weaver CH, Buckner CD et al. High-dose associatedwith an excellent relapse-free survival andlow cyclophosphamide, carmustine, and etoposide followed by transplant-related mortality. Our study results add to the allogeneic bone marrow transplantation in patients with available data supporting the use of CBV as an alternative lymphoidmalignancies who hadreceivedprior dose-limiting to TBI-containing regimens in lymphoma. NHL patients radiation therapy. J Clin Oncol 1995; 13: 596–602.

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