INTRODUCTION — The results of treatment of adults with acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) have steadily improved, and currently complete remission (CR) can be induced in 75 to 90 percent of patients. However, in contrast to ALL/LBL in children, relapses are common and long-term survival rates are approximately 25 to 50 percent, depending upon patient age and disease characteristics [1,2]. (See "Induction therapy for Philadelphia chromosome negative acute lymphoblastic leukemia in adults".)
Allogeneic hematopoietic cell transplantation (HCT) is frequently used for management of ALL/LBL in adults. Allogeneic HCT uses intensive preparative therapy (also called conditioning therapy; ie, chemotherapy and/or radiation therapy) to reduce the burden of leukemic blasts; blood cell formation is restored by engraftment of hematopoietic stem and progenitor cells from another individual (the donor). Allogeneic HCT can be used as consolidation therapy in first complete remission (CR) of ALL/LBL for selected patients with adverse clinical/pathologic features and for some patients in second CR (ie, after experiencing a relapse) or with primary refractory ALL/LBL
This topic discusses general issues in HCT for ALL/LBL in adults, including donor selection, preparative regimens, and the graft-versus-leukemia (GVL) effect.
Indications for allogeneic HCT and outcomes in various clinical settings are presented separately. (See "Post-remission therapy for Philadelphia chromosome negative acute lymphoblastic leukemia in adults" and "Post-remission therapy for Philadelphia chromosome positive acute lymphoblastic leukemia in adults" and "Treatment of relapsed or refractory acute lymphoblastic leukemia in adults".)
DEFINITIONS AND CONCEPTS — Allogeneic HCT plays important roles in management of adult patients with ALL/LBL.
Important definitions, concepts, and components of allogeneic HCT include:
●Allogeneic HCT – Allogeneic HCT uses intensive preparative therapy (also called conditioning therapy) to reduce the burden of leukemic blasts and restores blood cell formation by infusing hematopoietic stem and progenitor cells from another individual. Allogeneic HCT is frequently used for adults with ALL/LBL.
●Conditioning (preparative) regimen – These terms refer to intensive chemotherapy and/or radiation therapy that reduces the burden of residual leukemic cells. However, the preparative regimen also reduces or eliminates the ability of the transplant host to restore blood cell formation, which necessitates rescue by a donor graft. Conditioning regimens are described as:
•Myeloablative conditioning (MAC) – MAC uses very high-dose ("supralethal") treatment that causes irreversible cytopenias and requires hematopoietic support.
•Nonmyeloablative (NMA) conditioning – NMA regimens cause modest cytopenias and can be given without hematopoietic support.
•Reduced-intensity conditioning (RIC) – RIC regimens do not fit the categories of MAC or NMA regimens; the cytopenias are reversible, but hematopoietic support is required.
The choice of conditioning regimen varies according to the disease setting and patient factors, but MAC regimens are preferred, as discussed below. (See 'Preparative chemoradiotherapy' below.)
●Graft donor – For patients with ALL/LBL, the graft source is generally from another individual (ie, allogeneic graft); autologous HCT (ie, use of the patient's own stored cells) is rarely used in this setting.
A matched sibling donor (MSD) or matched unrelated donor (MUD) is generally preferred, but other options include a partially matched haploidentical family member donor or umbilical cord blood (UCB).
Donor selection for transplantation in ALL/LBL is discussed below. (See 'Donor selection' below.)
●GVHD and GVL – Immune cells from a non-identical graft donor may recognize tissues in the transplant recipient (the host) as foreign.
•Graft-versus-host disease (GVHD) – GVHD refers to multisystem disorders in which donor immune cells damage normal host tissues. Acute GVHD (aGVHD) and chronic GVHD (cGVHD) are distinct syndromes that differ in time course, affected organs, and clinical manifestations, as described separately. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease" and "Clinical manifestations and diagnosis of chronic graft-versus-host disease".)
•Graft-versus-leukemia effect (GVL) – GVL refers to the immune-mediated reaction of donor lymphocytes against residual leukemic blasts. The extent of GVL against ALL/LBL blasts is uncertain, but along with the preparative regimen, it contributes to eradication of residual leukemic cells. (See 'Graft-versus-leukemia' below.)
TRANSPLANT SETTINGS — Allogeneic HCT can be effective for control of ALL/LBL in several clinical settings:
●Consolidation in CR1 – Allogeneic HCT can be used as consolidation therapy after achieving first complete remission (CR1) in selected patients with adverse clinical or pathologic features.
Allogeneic HCT may be used for:
•Adverse pathologic features – Examples include t(9;22)/BCR::ABL1 rearrangement (ie, Philadelphia chromosome [Ph]-positive ALL/LBL) and Ph-like ALL/LBL. (See "Post-remission therapy for Philadelphia chromosome positive acute lymphoblastic leukemia in adults".)
•Residual measurable residual disease (MRD) – Persistent presence of MRD after remission induction or consolidation phase. (See "Post-remission therapy for Philadelphia chromosome negative acute lymphoblastic leukemia in adults".)
●Consolidation after relapsed ALL/LBL – Allogeneic HCT can be used as consolidation in second CR (CR2; remission after disease relapse). (See "Treatment of relapsed or refractory acute lymphoblastic leukemia in adults".)
●Primary refractory ALL/LBL – Allogeneic HCT has a potential role in selected patients who did not achieve CR1. (See "Treatment of relapsed or refractory acute lymphoblastic leukemia in adults".)
DONOR SELECTION — The preferred donor for patients undergoing allogeneic HCT for ALL is a human leukocyte antigen (HLA)-matched sibling or matched unrelated donor (MUD). However, fewer than 25 percent of patients in the transplantable age group have an HLA-matched sibling donor. Allogeneic HCT using a partially matched family member donor or umbilical cord blood is a reasonable option for patients who do not have an HLA-identical matched donor [2-4]. (See "Sources of hematopoietic stem cells".)
Matched unrelated donor — There has been steady improvement in the outcome of patients undergoing MUD-HCT, largely due to better matching at the HLA loci using molecular methods for DNA sequencing instead of serology alone [5-7]. Treatment-related mortality (TRM) is still high using this treatment modality, and it increases further with age. However, MUD-HCT is generally available now for adults up to 65 to 70 years of age. (See "Donor selection for hematopoietic cell transplantation", section on 'Unrelated donors'.)
●Assessment of the efficacy of MUD-HCT for adults with ALL is difficult because most available data come from registries and include a large proportion of children. The range of findings can be illustrated by the following studies:
●The European Group for Blood and Marrow Transplantation (EBMT) retrospectively compared 191 MUD-HCT recipients with 382 autologous HCT recipients for acute leukemia . Patients were matched for diagnosis, age, stage of disease, and year of transplantation. TRM was higher with MUD-HCT (44 versus 15 percent) but the relapse rate was lower (32 versus 55 percent). The two-year leukemia-free-survival (LFS) for all patients with ALL was similar in both groups (39 and 32 percent).
●Another series compared the results of 337 patients with ALL who received MUD-HCT (only 36 percent of whom were more than 18 years of age) with 214 patients with ALL who underwent autologous HCT during the period from 1987 to 1993 . The TRM for adults undergoing MUD-HCT in second complete remission (CR2) was 48 percent and was even higher for other stages of disease (57 to 68 percent). The relapse rate was approximately 26 percent at one year. For adults in CR2, MUD-HCT yielded an LFS of 42 percent compared with zero percent after autologous HCT.
●A review of the experience (1988 to 1990) with MUD-HCT facilitated by the National Marrow Donor Program (NMDP) described 127 adults with poor risk ALL [ie, presence of t(9;22), t(4;11), or t(1;19)], with an age range from 16 to 54 years . At two years, the cumulative incidence of TRM was 61 percent, while overall survival (OS) was 40, 17, and 5 percent for patients transplanted in CR1, CR2 or CR3, or relapsed or resistant disease, respectively. For patients transplanted in CR1, OS was 32 percent at four years, with a cumulative incidence of relapse of 13 percent. Independent predictors of better disease-free survival were:
•Transplantation in CR1
•Short interval of time between diagnosis and transplantation
•HLA matching at the DRB1 locus
•Cytomegalovirus-negative status for both donor and host
•Presence of the Philadelphia chromosome, t(9;22)
●A subsequent retrospective review of 169 adult patients with Philadelphia chromosome-negative ALL who received unrelated donor transplants in CR1 reported five-year rates of TRM, relapse, and OS of 42, 20, and 39 percent, respectively . The vast majority of patients had at least one feature of poor risk disease. Factors associated with a worse outcome included white blood cell (WBC) count more than 100 x 109/L, time to CR1 >8 weeks, cytomegalovirus seropositivity, HLA mismatching, and T cell depletion.
Compared with matched related donor transplants, MUD HCT appears to result in similar survival rates, but higher rates of nonrelapse mortality (NRM). A retrospective analysis of 641 adults who underwent allogeneic HCT in CR1 compared the outcomes of patients who underwent related HCT (48 percent) with those who underwent MUD HCT in Japan between 1993 and 2007 . When compared with those with a related donor, patients with an unrelated donor had similar survival rates (62 versus 65 percent at four years), lower relapse rates (22 versus 32 percent), higher rates of NRM (27 versus 14 percent), and higher rates of grade II-IV acute graft-versus-host disease (GVHD; 42 versus 30 percent).
Partially matched family member — Another option, which would significantly increase donor availability, is to use T cell-depleted stem cells from related donors with one fully mismatched HLA haplotype [11-13]. (See "Donor selection for hematopoietic cell transplantation" and "HLA-haploidentical hematopoietic cell transplantation".)
One study evaluated this approach in 101 assessable patients with high-risk acute leukemia (AML and ALL), with the following results :
●Full engraftment was achieved in 100 patients; acute or chronic GVHD developed in 5 and 7 percent of evaluable patients, respectively.
●NRM was 38 percent. Relapse rates for those transplanted in remission or relapse were 14 and 45 percent, respectively.
●Event-free survival was 46 percent for the 24 patients with ALL receiving HCT while in remission.
PREPARATIVE CHEMORADIOTHERAPY — Preparative regimens are generally divided into three categories: myeloablative, nonmyeloablative, and reduced-intensity regimens. Most studies of allogeneic HCT in ALL have used myeloablative preparative regimens. (See "Preparative regimens for hematopoietic cell transplantation", section on 'Definitions'.)
Myeloablative preparative regimens use very high, "supralethal," doses of chemotherapy and/or radiation in an attempt to improve upon the results of conventional treatment. The use of these doses is based upon the dose-response relationship observed in hematologic malignant diseases in general and in ALL in particular .
Relapse of disease is responsible for a large proportion of failures from allogeneic HCT in ALL, suggesting that current conditioning regimes do not eradicate tumor cells sufficiently. Further intensification is limited by parallel increases in treatment-related mortality (TRM). There is no generally agreed-upon best preparative regimen prior to transplant regimen, although total body irradiation (TBI) plus cyclophosphamide is the most widely used. For older patients, reduced-intensity conditioning regimens are increasingly used .
Total body irradiation (TBI) — TBI is either fractionated over three to five days or given as a single dose. Fractionated TBI is less toxic to normal cells but large radiation doses are more effective at killing resistant tumor cells. Studies in adults with ALL found that single dose TBI was associated with a significantly higher TRM but also a lower relapse rate than fractionated TBI; there was no difference in the overall leukemia-free survival (LFS) .
TBI is an important risk factor for the development of cataracts, the incidence of which is higher with single dose than fractionated TBI [16,17]. In one study of 2149 patients with acute leukemia, from the European Group for Blood and Marrow Transplantation registry, the overall 10-year estimated cataract incidence was 60 percent with single dose TBI, 43 percent with fractionated TBI with six or less fractions, and 7 percent with fractionated TBI with more than six fractions .
Chemotherapy in combination with TBI — The combination of TBI plus cyclophosphamide is the most common preparative regimen used prior to allogeneic HCT for ALL. Agents other than cyclophosphamide have been evaluated in combination with TBI in attempts to further intensify the conditioning regimen. Cytosine arabinoside (cytarabine), for example, has potent antileukemic activity, although the data do not indicate a benefit compared with cyclophosphamide [18-21]. (See "Preparative regimens for hematopoietic cell transplantation", section on 'Radiation (RT)-containing regimens'.)
●A study of 68 consecutive patients with poor-risk ALL treated with single dose TBI and 12 doses of high-dose cytarabine revealed a disease-free survival (DFS) of 18 percent at three years . These results were not different from the outcome of patients treated previously at the same institution with cyclophosphamide-containing regimens.
●In another report of 123 patients with ALL, conditioning regimens with TBI plus cyclophosphamide or cytarabine yielded similar outcomes, although TBI plus high-dose cytarabine was associated with a higher TRM .
Other studies have examined the role of TBI plus high-dose etoposide as a preparative regimen. Examples include:
●A trial that included 34 patients with ALL transplanted in first complete remission (CR1) reported three-year DFS and relapse rates of 64 and 12 percent, respectively .
●In a multicenter trial, patients with advanced acute leukemia (including 47 patients with ALL beyond CR1) were randomly assigned to treatment with either fractionated TBI plus high-dose etoposide or high-dose busulfan plus cyclophosphamide prior to allogeneic HCT . The regimens did not differ significantly with respect to toxicity, incidence of acute graft-versus-host disease (GVHD), overall survival (OS), or DFS.
Randomized trials of TBI-etoposide versus TBI-cyclophosphamide conditioning regimens have not been published. However, a retrospective registry-based study evaluated more than 500 adult and pediatric patients with relapsed ALL who underwent allogeneic HCT with one of these two regimens . For patients in second complete remission (CR), TBI plus etoposide was associated with reduced rates of relapse, treatment failure, and mortality, but the advantage for etoposide was overcome when a TBI dose ≥13 Gy was used together with cyclophosphamide; there were no differences in clinical outcomes for patients in CR1.
Chemotherapy without TBI — Attempts have been made to replace TBI in order to improve the antileukemic effectiveness of the conditioning regimen and to reduce TRM and long-term complications. Several regimens have been evaluated, and the most frequently studied has been the combination of busulfan and cyclophosphamide (Bu/Cy). LFS with this regimen is comparable to that obtained with radiation-containing regimens with greater ease of administration. It is not yet known if the incidence of delayed toxic effects such as sterility, cataracts, and secondary malignancy will be different.
●Data reported to the International Bone Marrow Transplant Registry (IBMTR) compared 70 patients with ALL conditioned with Bu/Cy to 286 patients conditioned with Cy-TBI; LFS and the rate of relapse were similar in the two groups .
●Another study evaluated the combination of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) as preparative therapy in 39 adults with ALL . Cyclosporine plus methotrexate or cyclosporine plus corticosteroids were given for GVHD prophylaxis. Twelve patients died from complications of treatment, 12 relapsed, and 15 survived free of leukemia. The LFS was 42 percent at three years for patients transplanted in CR or at first relapse but only 14 percent at one year for patients with more advanced disease. The incidence of chronic GVHD was high in this study (63 percent) but was associated with improved LFS.
Reduced-intensity conditioning — Reduced-intensity preparative regimens (RIC) are an intermediate category of regimens that do not fit the definition of myeloablative or nonmyeloablative. However, such regimens cause marked cytopenias, which may be prolonged and result in significant morbidity and mortality; hematopoietic stem cell support is required. (See "Preparative regimens for hematopoietic cell transplantation", section on 'Definitions'.)
A study of the IBMTR compared the outcomes of 93 adults with Philadelphia chromosome-negative ALL in first or second CR who underwent RIC matched sibling or unrelated donor transplantation with 1428 patients receiving full-intensity conditioning in the same setting . The group that received RIC was older (median age 45 versus 28 years) and more likely to receive a peripheral blood graft (73 versus 43 percent) but otherwise had similar prognostic factors. The two groups demonstrated similar age-adjusted survival rates and transplant-related mortality. There was a trend towards less acute and chronic GVHD.
A second retrospective study from the European Group for Blood and Marrow Transplantation assessed outcomes in 576 older adults (≥45 years) with ALL who underwent RIC (127 patients) or myeloablative (449 patients) allogeneic HCT from matched siblings . After a median follow-up of 16 months, RIC resulted in lower nonrelapse mortality (21 versus 29 percent) and a higher rate of relapse (47 versus 31 percent) at two-years. Estimated OS rates at two years were similar (48 versus 45 percent).
Prospective studies are needed to further define the role of RIC in patients with ALL .
GRAFT-VERSUS-LEUKEMIA — A number of observations have provided evidence for the existence of a graft-versus-leukemia (GVL) effect in ALL. Relapse rates are higher after syngeneic or T cell-depleted grafts compared with unmanipulated sibling grafts. As an example, a review from 163 transplant centers compared the results of 103 identical twin and 1030 human leukocyte antigen (HLA)-identical sibling transplants for leukemia . The three-year probability of relapse of leukemia was substantially higher in the identical twin transplants for acute myeloid leukemia (AML; 52 versus 16 percent), and for chronic myeloid leukemia (CML; 40 versus 7 percent); the GVL effect was less pronounced and not statistically significant for ALL (36 versus 26 percent). (See "Biology of the graft-versus-tumor effect following hematopoietic cell transplantation".)
Other observations have supported a GVL effect in ALL:
●Graft-versus-host disease (GVHD), both chronic and acute, has been associated with a lower rate of relapse.
●Regression of relapsed leukemia has occasionally been noted when GVHD flared following the discontinuation of immunosuppression.
●In one study of 84 patients with CML, 23 with AML and 22 with ALL in relapse after HCT, infusions of donor lymphocytes (DLI) were capable of inducing remission in CML (73 percent) and AML (29 percent). There was no response in the patients with ALL . In other reports, however, occasional patients with relapsed ALL have responded to DLI [31,32].
Thus, the existence of a beneficial allogeneic GVL effect against ALL cells is likely, but its magnitude is still a matter of controversy. Assuming that GVL does operate in ALL, its effect appears to be less powerful than that observed against myeloid leukemias, such as CML [29,30,33] (see "Immunotherapy for the prevention and treatment of relapse following allogeneic hematopoietic cell transplantation"). The high relapse rate (over 50 percent) among patients transplanted for advanced ALL may be due in part to the minimal effectiveness of this immunologic reaction. (See "Post-remission therapy for Philadelphia chromosome negative acute lymphoblastic leukemia in adults".)
LONG-TERM OUTCOMES — The Late Effects Working Committee of the International Bone Marrow Transplant Registry (IBMTR) studied 1458 patients with ALL treated with allogeneic HCT between 1980 and 1993 who were alive and free of disease for at least two years after transplantation . At a median follow-up of 6.7 years, 167 of these patients had died (11 percent). The causes of death were:
●Relapse of ALL – 48 percent
●Graft-versus-host disease (GVHD) – 23 percent
●New cancer – 10 percent
●Organ failure (liver, cardiac, pulmonary, renal) – 9 percent
●Infection without GVHD – 4 percent
●Other (hemorrhage, interstitial pneumonia, drug reaction, miscellaneous) – 8 percent
The relative risks for late death were 3.6, 2.0, and 1.9 for age at transplantation >40, transplantation while not in remission, and female donor with male recipient, respectively. A Karnofsky performance score of more than 90 (table 1) was noted in 89 percent of the survivors.
The presence of GVHD is an important post-transplant prognostic factor. GVHD has been associated with a lower incidence of relapse (a presumed reflection of the graft-versus-leukemia effect) [20,35,36] but also a shortened patient survival . Similarly, the use of GVHD prophylaxis without methotrexate or corticosteroids has been associated with an increased rate of relapse [37,38].
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Acute lymphoblastic leukemia (ALL) treatment in adults (Beyond the Basics)" and "Patient education: Hematopoietic cell transplantation (bone marrow transplantation) (Beyond the Basics)")
●Definitions/concepts – Hematopoietic cell transplantation (HCT) uses intensive treatment to reduce the burden of leukemic blasts; blood cell formation is restored by engraftment of hematopoietic stem and progenitor cells. Allogeneic HCT (ie, transplantation using a graft from another individual) can play an important role for adults with acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL); by contrast, autologous HCT (stored cells from the patient, him/herself) is rarely used with this disease. (See 'Definitions and concepts' above.)
●Graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect – Both GVHD and GVL occur only with allogeneic HCT.
•GVHD – Acute GVHD (aGVHD) and chronic GVHD (cGVHD) are distinct multisystem disorders that affect diverse organ systems and have different time courses. GVHD occurs when immune cells transplanted from a non-identical donor (the graft) recognize the transplant recipient (the host) as foreign, thereby initiating an immune reaction that causes disease in the host. (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease" and "Clinical manifestations and diagnosis of chronic graft-versus-host disease".)
•GVL – GVL results from immunologic effects of donor T cells against residual leukemic cells (GVL). GVL appears to be less robust against ALL/LBL than it is for other hematologic malignancies. (See 'Graft-versus-leukemia' above.)
●Settings – Transplantation is used for consolidation therapy after first complete remission (CR) in selected patients with high-risk clinical or pathologic features, as consolidation after achieving CR following relapse, and for primary refractory ALL/LBL. Selection of HCT in each of these settings must weigh the benefits and adverse effects of transplantation against other therapeutic options. (See 'Transplant settings' above.)
●Donor selection – For allogeneic HCT, the preferred donor is a human leukocyte antigen (HLA)-matched sibling donor (MSD) or a matched unrelated donor (MUD). When MSD nor MUD grafts are not available, other options include a partially matched haploidentical family member donor or umbilical cord blood (UCB). (See 'Donor selection' above.)
●Conditioning – Conditioning regimens (also called preparative regimens) are generally divided into (see 'Preparative chemoradiotherapy' above):
•Myeloablative conditioning (MAC) – MAC uses very high doses of chemotherapy and/or radiation therapy (RT) that cause irreversible cytopenias and require hematopoietic support.
•Nonmyeloablative (NMA) conditioning – NMA regimens cause modest cytopenias and can be given without hematopoietic support.
•Reduced-intensity conditioning (RIC) – RIC regimens do not fit the categories of MAC or NMA regimens; the cytopenias are reversible, but hematopoietic support is required.
There is no preferred conditioning regimen for all patients. Choice of a conditioning regimen varies with disease setting eg, first versus later CR), graft source, and patient factors (eg, age, comorbid conditions). However, MAC regimens are preferred, when possible
●Outcomes – Rates of survival, relapse, GVHD, and transplant-related mortality (TRM) vary with the disease setting, graft source, conditioning regimen, and patient factors. (See 'Long-term outcomes' above.)
1 : Hematopoietic stem cell transplantation rates and long-term survival in acute myeloid and lymphoblastic leukemia: real-world population-based data from the Swedish Acute Leukemia Registry 1997-2006.
2 : The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukemia: update of the 2006 evidence-based review.
3 : Impact of a donor source on adult Philadelphia chromosome-negative acute lymphoblastic leukemia: a retrospective analysis from the Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation.
5 : Autologous versus unrelated donor allogeneic marrow transplantation for acute lymphoblastic leukemia.
6 : High resolution HLA matching associated with decreased mortality after unrelated bone marrow transplantation.
7 : Donor search or autografting in patients with acute leukaemia who lack an HLA-identical sibling? A matched-pair analysis. Acute Leukaemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation (EBMT) and the International Marrow Unrelated Search and Transplant (IMUST) Study.
8 : Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome.
9 : Unrelated donor transplants in adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission.
10 : Allogeneic stem cell transplantation for adult Philadelphia chromosome-negative acute lymphocytic leukemia: comparable survival rates but different risk factors between related and unrelated transplantation in first complete remission.
11 : Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse.
12 : Haploidentical hematopoietic stem cell transplantation in adults with Philadelphia-negative acute lymphoblastic leukemia: no difference in the high- and low-risk groups.
13 : HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide.
15 : Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia in first complete remission: factors predictive of transplant-related mortality and influence of total body irradiation modalities.
17 : Cataracts after total body irradiation and bone marrow transplantation in patients with acute leukemia in complete remission: a study of the European Group for Blood and Marrow Transplantation.
18 : Bone marrow transplantation for acute lymphocytic leukemia utilizing total body irradiation followed by high doses of cytosine arabinoside: lack of superiority over cyclophosphamide-containing conditioning regimens.
19 : Bone marrow transplantation for acute leukemia and lymphoma with high-dose cytosine arabinoside and total body irradiation.
21 : Allogeneic bone marrow transplantation for acute lymphoblastic leukaemia: risk factors and clinical outcome.
22 : Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission.
23 : A prospective randomized comparison of total body irradiation-etoposide versus busulfan-cyclophosphamide as preparatory regimens for bone marrow transplantation in patients with leukemia who were not in first remission: a Southwest Oncology Group study.
24 : A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission.
25 : Conditioning for allogeneic marrow transplantation in patients with lymphohematopoietic malignancies without the use of total body irradiation.
26 : Radiation-free preparation for allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia.
27 : The outcome of full-intensity and reduced-intensity conditioning matched sibling or unrelated donor transplantation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first and second complete remission.
28 : Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation.
31 : Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation.
32 : Transfusion of donor peripheral blood buffy coat cells as effective treatment for relapsed acute leukemia after transplantation of allogeneic bone marrow or peripheral blood stem cells from the same donor.
33 : Sensitivity of hematological malignancies to graft-versus-host effects: an EBMT megafile analysis.
34 : Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry.
35 : The significance of graft-versus-host disease and pretransplantation minimal residual disease status to outcome after allogeneic stem cell transplantation in patients with acute lymphoblastic leukemia.
36 : Risk factors for adults with Philadelphia-chromosome-positive acute lymphoblastic leukaemia in remission treated with allogeneic bone marrow transplantation: the potential of real-time quantitative reverse-transcription polymerase chain reaction.
37 : Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival.
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