Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant

Severe regimen-related toxicity often complicates second transplant procedures performed in patients with hematological malignancies that have relapsed after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melphalan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients received allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative. Diagnoses included AML (n = 9), ALL (n = 1), or Hodgkin's disease (n = 1). Only one patient was in complete remission at the time of second transplant. The median interval between first transplant and relapse was 163 days (range 58-1885). Recipients of HLA-mismatched transplants received antithymocyte globulin in addition to fludarabine and melphalan as part of the conditioning regimen. All 11 patients received acute GVHD prophylaxis consisting of tacrolimus and methotrexate. Ten of 11 patients achieved hematopoietic engraftment with a median time to absolute neutrophil count >0.5 x 10(9)/l and to platelet count of >20 x 10(9)/l of 14 and 19 days, respectively. All engrafting patients achieved 100% donor chimerism on initial analysis, except for one with persistent leukemia at day +19. Two patients experienced grade 3 regimen-related toxicity, manifesting as acute renal failure. Acute GVHD grades 2-4 occurred in two recipients and chronic GVHD in four. The 100-day mortality from all causes was 36%. Ten of 11 patients (91%) died a median of 140 days (range 9-996) after the second transplant. The causes of death included relapse (n = 5), sepsis (n = 4), and idiopathic pneumonia syndrome (n = 1). One patient with AML survives in remission at 880 days post-transplant. We conclude that fludarabine- and melphalan-based conditioning promotes full donor chimerism, even following HLA-mismatched transplants. However, the regimen may be more beneficial when applied to patients undergoing allogeneic HSC transplantation earlier in their disease course.     

Molecular remission of CML after autotransplantation followed by adoptive transfer of costimulated autologous T cells

Four patients with chronic myelogenous leukemia (CML) that was refractory to interferon alpha (two patients) or imatinib mesylate (two patients), and who lacked donors for allogeneic stem cell transplantation, received autotransplants followed by infusions of ex vivo costimulated autologous T cells. At day +30 (about 14 days after T-cell infusion), the mean CD4+ cell count was 481 cells/microl (range 270-834) and the mean CD8+ count was 516 cells/microl (range 173-1261). One patient had a relative lymphocytosis at 3.5 months after T-cell infusion, with CD4 and CD8 levels of 750 and 1985 cells/microl, respectively. All the four patients had complete cytogenetic remissions early after transplantation, three of whom also became PCR negative for the bcr/abl fusion mRNA. One patient, who had experienced progressive CML while on interferon alpha therapy, became PCR- post transplant, and remained in a molecular CR at 3.0 years of follow-up. All the four patients survived at 6, 9, 40, and 44 months post transplant; the patient who remained PCR+ had a cytogenetic and hematologic relapse of CML, but entered a molecular remission on imatinib. Autotransplantation followed by costimulated autologous T cells is feasible for patients with chronic phase CML, who lack allogeneic donors and can be associated with molecular remissions.     

Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses.

Nonmyeloablative allogeneic stem cell transplantation has recently been explored as a safer alternative to conventional high-dose transplant regimens. Although a high incidence of mixed chimerism after nonmyeloablative procedures has been reported, the exact kinetics of engrafting donor cells in specific cellular lineages has yet to be defined. We investigated lineage-specific chimerism in 15 patients receiving an allogeneic peripheral blood stem cell (PBSC) transplant from an HLA-identical (n = 14) or a 5/6 antigen-matched sibling donor after a preparative regimen of cyclophosphamide and fludarabine. Donor chimerism was assessed weekly in T lymphocytes and myeloid cells by polymerase chain reaction (PCR) of minisatellite regions. Eight patients survived between 121 to 409 days after transplant. Ten of 14 patients surviving more than 30 days (71.4%) had delayed disease regression consistent with a graft-versus-malignancy (GVM) effect. One patient rejected the transplant with subsequent recovery of autologous hematopoiesis. Hematological recovery was rapid (median, 11 days to >/=500 neutrophils/microL) and was initially predominantly recipient in origin. Donor myeloid chimerism gradually supplanted recipient hematopoiesis and became fully donor in all survivors by 200 days after transplantation. In contrast, T-cell engraftment was more rapid, with full chimerism in 7 patients by day 30 and in 6 further patients by day 200 after cyclosporine withdrawal and donor lymphocyte infusion. Full donor T-cell engraftment preceded donor myeloid engraftment, acute graft-versus-host disease, and disease regression, consistent with a requirement for 100% donor T-cell chimerism for full expression of the alloresponse. These results emphasize the importance of lineage-specific chimerism analysis to successfully manipulate engraftment after nonmyeloablative allogeneic PBSC transplantation.     

Syngeneic transplantation in multiple myeloma - a case-matched comparison with autologous and allogeneic transplantation. European Group for Blood and Marrow Transplantation.

Twenty-five patients with multiple myeloma received bone marrow grafts (n = 24) or peripheral blood stem cells (n = 1) from twin donors. The outcome was compared in a case-matched analysis to 125 patients who underwent autologous transplantation, and 125 who underwent allogeneic transplantation. Seventeen patients (68%) receiving twin transplants entered complete remission, which was not significantly different from that of autologous (48%) or allogeneic (58%) transplants. The median overall and progression-free survival for the twins was 73 and 72 months, respectively. The overall survival tended to be better (73 vs 44 months) and the progression-free survival was significantly better (72 vs 25 months) than with autologous transplantation and both were significantly better than with allogeneic transplantation. Three of 17 patients who entered complete remission following transplantation had relapsed at follow-up. This relapse rate was significantly lower than following autologous transplantation and similar to the relapse rate with allogeneic transplantation. Only two twins died of transplant-related toxicity. Six further patients died of progressive or relapsing disease. Syngeneic transplantation in multiple myeloma appears to be the treatment of choice if a twin donor is available. A lower relapse risk than in autotransplantation may be due to reinfusion of malignant cells in some patients treated with this modality or to the presence of a graft-versus-myeloma effect in some syngeneic transplants.     

Low transplant-related mortality after second allogeneic peripheral blood stem cell transplant with reduced-intensity conditioning in adult patients who have failed a prior autologous transplant

Standard allogeneic stem cell transplantation (SCT) has been associated with a high transplant-related mortality (TRM) in patients who have failed a prior autologous SCT (ASCT). Reduced-intensity conditioning (RIC) regimens may reduce the toxicities and TRM of traditional myeloablative transplants. We report 46 adults who received a RIC peripheral blood SCT from an HLA-identical sibling in two multicenter prospective studies. The median interval between ASCT and allograft was 16 months, and the patients were allografted due to disease progression (n = 43) and/or secondary myelodysplasia (n = 4). Conditioning regimens consisted of fludarabine plus melphalan (n = 41) or busulphan (n = 5). The 100-day incidence of grade II-IV acute graft-versus-host disease (GVHD) was 42% (24% grade III-IV), and 10/30 evaluable patients developed chronic extensive GVHD. Early complete donor chimerism in bone marrow and peripheral blood was observed in 35/42 (83%) patients, and 16 evaluable patients had complete chimerism 1 year post transplant. With a median follow-up of 358 days (450 in 29 survivors), the 1-year incidence of TRM was 24%, and the 1-year overall (OS) and progression-free survival were 63% and 57%, respectively. Patients who had chemorefractory/ progressive disease, a low performance status or received GVHD prophylaxis with cyclosporine A alone (n = 32) had a 1-year TRM of 35% and an OS of 46%, while patients who had none of these characteristics (n = 32) had a 1-year TRM of 35% and an OS of 46% while patients who had none of these characteristics (n = 14) had a TRM of 0% and an OS of 100%. Our results suggest that adult patients who fail a prior ASCT can be salvaged with a RIC allogeneic PBSCT with a low risk of TRM, although patient selection has a profound influence on early outcome.     

Autologous bone marrow transplantation for acute myeloid leukaemia in remission: a preliminary report

Autologous bone marrow transplantation, using unpurged cryopreserved autologous marrow, was performed on ten adult patients with acute myeloid leukaemia in remission. Seven patients were in first chemotherapy-induced remission of their disease, while three were in later remission. Patients ages ranged from 24 to 52 years, with a median of 38.5 years. Conditioning therapy consisted of oral busulphan 16 mg/kg over four days and intravenous cyclophosphamide 60 mg/kg on two days. Bone marrow cells were thawed and infused two days later. All patients showed signs of marrow engraftment, however this was delayed in comparison with patients receiving allogeneic transplants. All patients developed fever requiring antibiotic therapy and one patient died of overwhelming sepsis. Another patient died of hepatic veno-occlusive disease two months after transplant. Serious, but non-fatal, hepatic complications occurred in two other patients. One patient, transplanted in third remission, relapsed 16 months post-autograft. No other relapses have been seen, with one second remission patient remaining leukaemia-free at 24 months, and six first remission patients in continuing remission 11 to 23 (median 20) months post transplant. These encouraging results require confirmation in a randomised clinical trial comparing autologous marrow transplantation versus standard chemotherapy.     

Early recurrence of rheumatoid arthritis after nonmyeloablative allogeneic blood stem cell transplantation in a patient with multiple myeloma

Allogeneic blood stem cell transplantation with reduced conditioning has been proposed as a new, potentially curative treatment option for patients with rheumatoid arthritis (RA). We report a 60-year-old woman with RA and coexisting multiple myeloma who was treated with high-dose melphalan and autologous blood stem cell transplantation (BSCT) followed by a nonmyeloablative allogeneic BSCT from her healthy dizygotic twin brother. She achieved a complete remission of her RA after autologous BSCT, but relapsed early despite complete donor chimerism following successful allogeneic transplantation with reduced intensity conditioning. This case illustrates that allogeneic BSCT following nonmyeloablative conditioning may be an uncertain option for curing patients with RA.     

A rapid dot-blot assay to assess chimerism following sex-mismatched bone marrow transplantation

Mixed chimerism may occur more frequently than previously thought following allogeneic bone marrow transplantation and may have implications in terms of relapse, graft-versus-host disease and immune reconstitution. DNA analysis using single or multilocus polymorphic probes cannot reliably discriminate between donor and recipient cells below a level of 10%. We used probe pHY2.1, a cloned segment of tandemly repeated DNA (2000 copies) on the long arm of chromosome Y. A dot blot procedure allowed us to immobilize DNA directly from 50 microliter of peripheral blood or bone marrow. Cross-reactivity was eliminated by hybridization at conditions of extreme stringency (65 degrees C, 50% formamide). Mixing experiments detected male DNA at a level of 0.1% after 10 h exposure. Five patients were studied serially post-bone marrow transplantation. One patient showed mixed chimerism for 12 months, one had complete autologous recovery and the remaining three showed complete engraftment. All results were verified by standard karyotyping on bone marrow cells. This technique is a simple, rapid and sensitive assay for chimerism following sex mismatched bone marrow transplantation.     

Myeloid and lymphoid chimerism after T-cell-depleted bone marrow transplantation: evaluation of conditioning regimens using the polymerase chain reaction to amplify human minisatellite regions of genomic DNA.

Determining both myeloid and lymphoid chimerism after T-cell-depleted allogeneic bone marrow transplantation (BMT) could be helpful in the understanding of the biology of engraftment and could provide a rational method of assessing the ability of different conditioning regimens to promote engraftment. We prospectively investigated the role of different pretransplant conditioning regimens in 29 leukemic patients post-BMT by assessing myeloid and T-cell chimerism using a rapid and sensitive polymerase chain reaction (PCR) method. Minisatellites are hypervariable regions of DNA consisting of tandem repeats of a core nucleotide sequence, and allelic polymorphism results from differences in the number of the repeats. We used this variation to distinguish between donor and recipient cells post-BMT. Seventeen patients (9 sibling and 8 unrelated donors) received conditioning with hyperfractionated total body irradiation (TBI), thiotepa, and cyclophosphamide (Cy). Of the other 12 patients (all sibling donors), 11 received TBI plus Cy plus another agent: VP16, carboplatinum, or AZQ. One patient received TBI plus thiotepa plus VP16. All but one of the patients studied received marrow from HLA-identical donors. PCR analysis confirmed donor lymphoid engraftment within 8 days of transplant in six of six patients studied. All granulocyte DNA was of donor origin within the first 4 weeks of transplant, regardless of the conditioning regimen. The day +28 T cells were exclusively of donor origin in 14 of 17 patients who received TBI plus thiotepa plus Cy, but were mixed chimeric in 10 of 12 patients who received other conditioning regimens (P < .001). Early graft rejection was seen in one unrelated transplant recipient conditioned with TBI plus thiotepa plus Cy. Late graft failure was observed in 3 of 12 patients with mixed T-cell chimerism and in none of 16 patients with full donor chimerism at day +28. However, 5 of 16 patients who had complete T-cell chimerism at day +28 developed acute graft-versus-host disease (GVHD), whereas no patient with mixed chimerism had acute GVHD. Our results indicate that minisatellite PCR is a rapid and sensitive method for assessing chimerism post-BMT, that the donor T cells are important for consistent durable engraftment, and that TBI plus thiotepa plus Cy may be superior to the other regimens studied in inducing full donor chimerism. Larger numbers and longer follow-up are necessary to confirm these data and also to assess the relationship between complete donor T-cell chimerism and leukemia-free survival.     

Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin

Patients with sickle cell disease (N = 3) and thalassemia (N = 1) with high-risk features received hematopoietic stem cell transplantations (HCT) to induce stable (full or partial) donor engraftment. Patients were 9-30 years of age. Fludarabine, rabbit anti-thymocyte globulin (ATG), and 200 cGy total body irradiation were administered pre-transplant. Patients received bone marrow (N = 3) or peripheral blood stem cells (N = 1) from HLA-identical siblings, followed by mycophenolate mofetil and cyclosporine for post-grafting immunosuppression. Significant lymphopenia, but only moderate neutropenia and thrombocytopenia developed post transplant. No grade IV nonhematological toxicities or acute graft-versus-host disease (GVHD) were observed. At 3 months after transplantation, three of four patients had evidence of donor myeloid chimerism (range, 15-100%). However, after post transplant immunosuppression was discontinued, graft rejection occurred in all but one patient. This patient is now doing well 27 months post transplant with full donor engraftment. One patient died after a second transplant, and another patient experienced a stroke as her graft was being rejected. These results suggest that stable donor engraftment after nonmyeloablative HCT is difficult to achieve among immunocompetent patients with hemoglobinopathies and that new approaches will need to be developed before wider application of this transplantation method for hemoglobinopathies.     

Nonmyeloablative stem cell transplantation in metastatic renal cell carcinoma: delayed graft-versus-tumor effect is associated with chimerism conversion but transplantation has high toxicity

Seven out of 29 patients with metastatic renal cell carcinoma (RCC) considered eligible for allogeneic stem cell transplantation underwent nonmyeloablative stem cell transplantation (NST) from HLA-identical donors. Conditioning comprised cyclophosphamide, fludarabine and antithymocyte globulin. Prolonged mixed chimerism (MC) after engraftment converted to complete donor chimerism (CC) after infusion of donor lymphocytes and/or graft-versus-host disease (GvHD) in six patients. Five patients developed severe GvHD. Two of seven patients had a delayed tumor response after conversion to CC. After a median follow-up of 10 months (4-24 months), 5/7 patients are alive, one in very good partial remission (PR), one with stable and three with progressive disease. One of the seven patients died from sepsis in PR and 1/7 died from rapid tumor progression after sustained MC. None of the 22 nontransplanted patients responded to further therapies. Survival after 1 year was 59% in transplanted and 66% in nontransplanted patients (n.s.). A pooled data analysis from the literature suggests a graft-versus-tumor effect after transplant in patients with metastatic RCC, which becomes effective after chimerism conversion. Available data demonstrate high nonrelapse mortality in these patients. NST in RCC still has to be regarded as an investigational approach requiring careful patients' selection and longer follow-up within clinical studies.     

Allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning in intermediate- or high-risk patients with myelofibrosis with myeloid metaplasia

A total of 21 patients with myelofibrosis with myeloid metaplasia (MMM), with a median age of 54 years (range, 27-68 years), were prepared with a reduced-intensity conditioning (RIC) regimen. The patients received an allogeneic marrow (n = 3) or peripheral blood stem-cell (n = 18) transplant from HLA-matched related (n = 18) or unrelated (n = 2), or 1 Ag-mismatched related (n = 1), donors. RIC regimens included fludarabine/total body irradiation 200 cGy (n = 5) or 450 cGy (n = 1), fludarabine/melphalan (n = 7), thiotepa/cyclophosphamide (n = 7), and thiotepa/fludarabine (n = 1). At the time of transplantation, all of the patients were at intermediate (n = 13) or high (n = 8) risk, according to the Dupriez classification. Of the patients, 19 had grade III or IV marrow fibrosis. All of the patients achieved full engraftment but one. Posttransplantation chimerism analysis showed more than 95% donor cells in 18 patients, while 2 patients achieved complete donor chimerism after donor leukocyte infusion (DLI). Acute graft-versus-host disease (GVHD) grades II to IV was observed in 7 patients, grades III to IV in 2, and extensive chronic GVHD in 8 of 18 evaluable patients. There were 3 patients who died from acute GVHD, infection, and relapse. There are 18 patients alive 12 to 122 months (median, 31 months) after transplantation, and 17 are in remission (1 after a second transplantation). The use of RIC regimens in allogeneic stem cell transplantation results in prolonged survival in intermediate/high-risk MMM patients.     

Minimal residual disease is more common in patients who have mixed T- cell chimerism after bone marrow transplantation for chronic myelogenous leukemia

Determining both lymphoid chimerism and the presence of minimal residual disease after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) could be helpful to the understanding of the biology of leukemic relapse in this disease. We prospectively investigated 32 patients with CML post-BMT by assessing T- cell chimerism and minimal residual disease using sensitive polymerase chain reaction (PCR) methodologies. Patients were studied between 1 and 24 months post-BMT. Thirty patients received a T-cell-depleted marrow grafts and 2 received unmanipulated marrow. All but 1 patient were conditioned with total body irradiation (TBI)+thiotepa+cyclophosphamide (Cy). The other patient received TBI+Cy as conditioning. The T cells were exclusively of donor origin in 12 of 16 patients who were tested at 1 month post-BMT, but were mixed chimeric in 11 of these patients by > or = 3 months. Once mixed T-cell chimerism was documented, no patient returned to having all donor T-cells. At a median follow-up of 12 months, minimal residual disease was present in 18 of 22 patients with mixed T-cell chimerism and in 3 of 10 patients with full donor chimerism. The actuarial molecular relapse rate at 24 months for the two groups is 91% and 33%, respectively (P < .02). The finding of BCR- ABL mRNA within the first 6 months of transplant or on two consecutive assays was highly predictive of subsequent cytogenetic or hematologic relapse (P = .032 and P < .02, respectively). Ten patients, 9 with mixed T-cell chimerism, have relapsed (4 clinical, 6 cytogenetic) at a median of 12 months post-BMT. These data suggest that mixed T-cell chimerism may be a marker for abrogation of graft-versus-leukemia activity that is thought to be pivotal in eradicating minimal residual disease after BMT for CML.     

Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients received additional donor lymphocyte infusions. Forty-six of 157 (25%) assessable patients responded to azacitidine therapy: 24 (15%) achieved a complete remission and 22 a partial remission. Response rates were higher in patients transplanted in complete remission (P=0.04) and those transplanted for myelodysplastic syndromes (P=0.023). In patients who achieved a complete remission, the 2-year overall survival was 48% versus 12% for the whole population. Overall survival was determined by time to relapse post transplant more than six months (P=0.001) and percentage of blasts in the bone marrow at time of relapse (P=0.01). The concurrent administration of donor lymphocyte infusion did not improve either response rates or overall survival in patients treated with azacitidine. An azacitidine relapse prognostic score was developed which predicted 2-year overall survival ranging from 3%–37% (P=0.00001). We conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required.     

Fludarabine-based preparative protocol for unrelated donor cord blood transplantation in children: successful engraftment with minimal toxicity

Unrelated umbilical cord blood (UCB) is a new source of hematopoietic stem cell (HSC) for allogeneic transplantation. The optimal conditioning for UCB transplant has not been defined. Intensive immunosuppression is frequently employed because of the higher risk of graft failure. Fludarabine monophosphate is shown to be an effective agent for facilitating allogeneic HSC engraftment. We have recently encountered three children who were not ideal candidates for 'conventional' conditioning protocols. TBI followed by fludarabine and melphalan were used for transplant preparation. The UCB units were one HLA-antigen (n = 1) and two HLA-antigen mismatched with the recipients. All three patients engrafted successfully. There was mild extramedullary toxicity. Two patients are alive with complete chimerism 8 and 20 months after transplant. A fludarabine-based protocol may be considered for selected cases of UCB transplants.     

Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect

Reduced intensity conditioning (RIC) for allogeneic stem cell transplantation allows stable donor cell engraftment with the maintenance of a graft versus malignancy effect. Many different regimens exist employing various combinations of chemotherapy, radiotherapy and T-cell depletion. We examined the role of non-T-cell depleted RIC regimens in 56 patients with haematological malignancies. Patients received fludarabine phosphate for 5 days (30 mg/m2 in 35 patients, 25 mg/m2 in 21 patients) and melphalan for 1 day (140 mg/m2 in 36 patients, 100 mg/m2 in 20 patients). Immunosuppression was with CyA alone in 33 patients and CyA/MTX in 23 patients. Twenty-four of the 26 patients with chimerism data showed >95% donor chimerism at 3 months post transplant. aGVHD occurred in 18% of patients receiving CyA/MTX compared to 53% of patients receiving CyA. The 100-day mortality rate was 0.16 (95%CI 0.08-0.28) and 1-year nonrelapse mortality was 0.24 (95%CI 0.13-0.38). Thirty-three patients remained alive and in CR at a median of 19 months post transplant (range 3-38 months). We have shown that patients transplanted with fludarabine phosphate, melphalan 100 mg/m2 and with CyA/MTX as post transplant immunosuppression can achieve good disease control with an acceptable level of toxicity. Further studies are required to confirm these findings.     

Treatment of lymphoma relapses after allogeneic hematopoietic stem cell transplantation with intensive chemotherapy followed by infusion of hematopoietic stem cell from the original donor

Five lymphoma patients relapsed from allogeneic hematopoietic stem cell transplantation (HSCT). Three patients who received myeloablative conditioning had full donor chimerism at relapse, whereas two who received nonmyeloablative conditioning had partially or completely lost the graft. All received mini-BEAM [carmustine (BCNU), etoposide, cytarabine (AraC), melphalan], followed by infusion of HSC (four peripheral blood, one marrow) from the initial donor. Neutropenia and thrombocytopenia were brief, and full donor chimerism was established in all cases. There were four complete and one partial remissions. Graft-versus-host disease occurred in three cases, all with full donor chimerism at relapse. Two patients died subsequently of disease relapse or progression. Another two patients died from fungal infection, one of whom was still in remission at death. One patient had remained in remission 47 months after treatment. Mini-BEAM/HSC is an effective treatment for lymphoma relapses after allogeneic HSCT, but optimal strategies of remission consolidation and prevention of treatment-related complications are needed to improve outcome.     

Allogeneic bone marrow transplantation for high risk non-hodgkin's lymphoma during first complete remission

Summary Allogeneic bone marrow transplantation from histocompatible sibling donors was performed in six patients with extranodal involvement of high grade lymphoma during first complete remission. Five patients had lymphoblastic lymphoma and one had diffuse undifferentiated lymphoma. The cytoreductive/immunosuppressive regimen consisted of total body irradiation and high dose cyclophosphamide. Four patients are alive in complete remission at 8 months, 14 months, 21 months and 47 months post transplantation. One patient who relapsed 7 months after his initial transplantation underwent a second transplantation but another relapse 17 months later led to his death. One patient died of chronic graft-versus-host disease and at autopsy there was no evidence of lymphoma. These data demonstrate that allogeneic bone marrow transplantation can produce durable remissions in patients with high grade lymphoma who present with bone marrow, central nervous system and/or skin involvement.