International Bone Marrow Transplant Registry Research Articles

Primary plasma cell leukemia: Report of 17 new cases treated with autologous or allogeneic stem‐cell transplantation and review of the literature

Primary plasma cell leukemia (PPCL) is a rare hematologic malignancy characterized by the proliferation of plasma cells in blood, bone marrow, and other organs in the absence of established multiple myeloma. PPCL has a poor prognosis when treated with conventional therapy for multiple myeloma. We describe here 17 new cases of PPCL who underwent stem-cell transplantation (SCT) (2 cases observed by the authors and 15 cases from the International Bone Marrow Transplant Registry [IBMTR]). The first case was diagnosed in a 21-year-old male who presented with leukocytosis and acute renal failure. He was treated with hyper-CVAD, entered complete remission, and then proceeded to high-dose chemotherapy with peripheral stem-cell support. He is currently in complete remission 23 months after initial diagnosis and 19 months after autologous SCT. The second case was observed in a 31-year-old male who presented with leukocytosis and hepatic infiltration with plasma cells. He was treated with VAD chemotherapy and underwent allogeneic bone marrow transplantation from his HLA-identical sister. He remained in complete remission for 3 years and then developed progressive refractory disease, dying 7 years after the initial diagnosis. In addition to these 2 cases, 15 further unpublished cases of PPCL from the IBMTR are reported here (treated between 1993 and 2001, 6 by autologous and 9 by allogeneic transplantation). Finally, the features of PPCL, the outcome, published data of SCT for PPCL, and indications for treatment are discussed.

Pairwise multiple comparison adjustment in survival analysis

Many clinical studies have as their endpoint the time until some event (such as death) occurs. Often in such studies researchers are interested in comparing several treatment or prognostic groups with one another in terms of their survival curves. When many such pairwise group comparisons are done, the chance of finding a false significance among all of the comparisons is inflated above the usual desired significance level. This paper investigates methods of adjusting the survival analysis for the number of comparisons being made. These methods are applied to a retrospective study conducted by the International Bone Marrow Transplant Registry and compared in a simulation study in terms of the power to detect actual differences in the survival curves between the groups.

Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry

Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used in patients with lymphoma who experience disease relapse after autologous hematopoietic stem cell transplantation (auto-HSCT) because the allograft is tumor free and may induce a graft-versus-tumor effect. We analyzed 114 patients treated with this approach from 1990 to 1999 to assess disease progression, progression-free survival (PFS), and overall survival (OS). Cumulative incidence of disease progression at 3 years was 52%, whereas treatment-related mortality was 22%, lower than previously reported. Three-year probabilities of OS and PFS were 33% and 25%, respectively. With prolonged follow-up, however, nearly all patients experienced disease progression, and 5-year probabilities were 24% and 5%, respectively. Complete remission at the time of allo-HSCT and use of total body irradiation (TBI) in patients with non-Hodgkin lymphoma (NHL) were associated with lower rates of disease progression and higher rates of OS. In summary, allo-HSCT is feasible for patients with lymphoma who have relapses after auto-HSCT and can result in prolonged survival for some, but it is usually not curative. Most likely to benefit are patients who have HLA-matched sibling donors, are in remission, and have good performance status.

131I-Anti-CD45 Antibody Plus Busulfan/Cyclophosphamide in Matched Related Transplants for Acute Myeloid Leukemia in First Remission.

Patients with AML in first remission undergoing conventional matched related hematopoietic cell transplantation (HCT) have a significant risk of both relapse and non-relapse mortality following transplant. In an attempt to improve outcome by decreasing relapse, we conducted a Phase I/II study in which targeted hematopoietic irradiation delivered by 131I-labeled anti-CD45 antibody is combined with busulfan (BU) and cyclophosphamide (CY). Patients (median age 41) received a trace (~5mCi) 131I-labeled dose of 0.5 mg/kg anti-CD45 (BC8) murine monoclonal antibody followed by serial quantitative gamma camera imaging and a bone marrow biopsy for estimation of radiation absorbed doses to target organs (marrow and spleen) and non-target organs (liver, lung, and kidney). Fifty-two of 59 patients (88%) had a higher estimated radiation absorbed dose to marrow and spleen than to any normal organ. Forty-six of these were treated with 102 to 298 mCi 131I delivering an estimated 5.3 to 19 (mean 11.3) Gy to bone marrow, 17 to 72 (mean 29.7) Gy to spleen, and 3.5 Gy (n = 4) to 5.25 Gy (n = 42) to the liver. Patients then received targeted BU (AUC 600–900 ng/ml), CY (120 mg/kg), and infusion of HLA-matched related marrow (n = 40) or peripheral blood stem cells (n = 6). The non-relapse mortality (NRM) was 17%, as eight patients died of transplant-related causes (sepsis-2, idiopathic pneumonia syndrome-1, viral pneumonia-3, and fungal pneumonia-2). Nine patients (20%) relapsed 3 to 38 months post-transplant, and 28 patients (61%) are surviving disease-free 7 to 124 months (median 49 months) post-transplant. For 26 patients (62%) with intermediate risk cytogenetics, 18 (69%) are surviving disease-free, with only 3 (12%) relapsing. Fifteen patients (33%) were considered high risk based on unfavorable cytogenetics or secondary AML; 7 of these 15 (46%) are surviving disease-free and 5 (33%) have relapsed. Because of the known impact of features such as age and cytogenetic risk group on post-HCT outcome, we compared our data to data from the International Bone Marrow Transplant Registry (IBMTR) on first remission AML patient conditioned with BU/CY alone prior to HCT. Over a 10-year period, 980 IBMTR patients (median age 28) were transplanted using a median BU dose of 16 mg/kg (range 8–21 mg/kg) and a median CY dose of 120 (range 62–232). Of the 509 IBMTR patients with known cytogenetics at diagnosis, 466 (92%) had intermediate-risk cytogenetics. Using a Cox regression model for overall mortality and adjusting for age and cytogenetics risk differences, the hazard for mortality among 131I-BC8 Ab/BU/CY patients is 0.65 times that of registry patients receiving BU/CY only (95% CI 0.35 to 1.08, p = 0.09). The addition of targeted hematopoietic irradiation to conventional BU/CY is both feasible and well tolerated, and has the potential to improve survival for patients undergoing HCT for AML in first remission.

Allogeneic Peripheral Blood Versus Bone Marrow Transplantation: Children Are Small Adults and More

This issue of the Journal of Clinical Oncology reports the controversial findings of the International Bone Marrow Transplant Registry retrospective review comparing allogeneic stem-cell sources— bone marrow (BM) versus granulocyte colony-stimulating factor (G-CSF) –mobilized peripheral-blood stem cells (PBSC)—in children and adolescents. In their review of 143 PBSC and 630 BM human leukocyte antigen–identical sibling donor transplants in children with leukemia aged 8 to 20 years, Eapen et al found a higher rate of chronic graft-versus-host disease (GVHD) and treatment-related mortality (with similar relapse risk) in children receiving PBSC compared with BM. Overall, there was poorer survival when PBSC were used as the donor source, even after adjusting for relative risks. This is an unsettling finding, given that in 2003, close to 30% of pediatric matched sibling transplants reported to the International Bone Marrow Transplant Registry used PBSC as the donor source. The shift in clinical practice from using BM to G-CSF– mobilized PBSC as the hematopoietic progenitor cell source has arguably been among the most rapid and sweeping changes in clinical hematopoietic allogeneic transplantation this decade, second only to changes in the management of chronic myelogenous leukemia after the introduction of imatinib. Since it is common practice in pediatrics to extrapolate from adult therapy, the transition has occurred in both pediatrics and adult transplantation. In general, this is a reasonable approach, especially if there are no clear developmental or physiologic reasons to expect differences in efficacy or toxicity between children and adults. The biologic differences between the two stem-cell products include differences in both intermediate hematopoietic progenitors and T cells. In multiple animal and human trials, there has consistently been a strong correlation between the number of T cells in the transplanted graft and development of GVHD. The 10-fold increase in T cells in a PBSC graft initially made allogeneic transplant physicians hesitant to use PBSC as a stem-cell product, but experience has shown that PBSC can be safely used as an allogeneic stem-cell source. In the process of mobilization, the T cells have been exposed to G-CSF, which is known to modify T-cell responses in the direction of the T-helper-2 response, potentially explaining the tolerable GVHD observed. Early, predominately adult, experience with PBSC, frequently in patients with advanced malignancies, demonstrated more rapid count recovery and less early transplantrelated mortality (TRM), which translated into improved survival. As reviewed in the article by Eapen et al, subsequent results of randomized trials have been mixed. The overall conclusion is that PBSC transplantation outcomes are at least equivalent to, if not better than, BM as an allogeneic stem-cell source. Hence, there has been a rapid transition in clinical practice to the use of G-CSF–mobilized PBSC as the allogeneic donor source, with the rationale that more rapid postcollection recovery of the donor and more rapid post-transplantation recovery of hematopoiesis (with resultant shortening of hospital stay and decreased early transplant-related mortality in patients, especially those with advanced disease or poor performance status at the time of transplantation) were all important outcome goals, even if survivals was equivalent. The transition of clinical practice to use of G-CSF– mobilized PBSC has been slower in pediatrics, partially due to concerns of donor safety since donors are often minors. With increased experience in young child apheresis, there has been a growing acceptance that even young children can safely receive G-CSF and undergo apheresis, as recently reviewed by the Pediatric Blood and Marrow Transplant Consortium. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 22 NUMBER 24 DECEMBER 15 2004

Higher Mortality After Allogeneic Peripheral-Blood Transplantation Compared With Bone Marrow in Children and Adolescents: The Histocompatibility and Alternate Stem Cell Source Working Committee of the International Bone Marrow Transplant Registry

Peripheral-blood stem cells (PBSC) may be used as an alternative to bone marrow (BM) for allogeneic transplantation. Despite lack of data on PBSC transplantation in children, there has been a change in clinical practice, with increasing numbers of children receiving PBSC allografts. We compared the results of 143 PBSC and 630 BM transplants from human leukocyte antigen-identical sibling donors in children aged 8 to 20 years with acute leukemia. PBSC transplant recipients were older, and were more likely to have advanced leukemia, receive growth factors post-transplantation, and have undergone transplantation more recently. Risks of acute and chronic graft-versus-host disease (GVHD), treatment-related mortality, relapse, treatment failure (relapse or death), and overall mortality were compared using Cox proportional hazards regression to adjust for potentially confounding factors. Hematopoietic recovery was faster after PBSC transplantation. Risks of grade 2 to 4 acute GVHD were similar, but chronic GVHD risk was higher after PBSC transplantation (relative risk [RR], 1.85; 95% CI, 1.28 to 2.66; P = .001). In contrast to reports in adults, treatment-related mortality (RR, 1.89; 95% CI, 1.28 to 2.80; P = .001), treatment failure (RR, 1.31; 95% CI, 1.03 to 1.68; P = .03), and mortality (RR, 1.38; 95% CI, 1.07 to 1.79; P = .01) were higher after PBSC transplantation. Risks of relapse were similar. These data suggest poorer outcomes after PBSC compared with BM transplantation in children after adjusting for relevant risk factors. Given the trend toward increased use of PBSC allografts in children, prospective clinical trials are required to determine their appropriate role in this group of patients.

Comparison of unrelated cord blood and unrelated bone marrow transplants for adults with leukemia a collaborative study: The New York blood center national cord blood program and The International bone marrow transplant registry

Though little is known regarding the safety and efficacy of umbilical cord blood (UCB) transplantation in adults, these are increasingly used in older subjects. We compared the results of 169, ≥1-antigen mismatched UCB, 83, 1-antigen mismatched and 367, matched bone marrow (BM) transplants in patients age 16–60 years with acute and chronic leukemia. Majority of UCB recipients were mismatched at 2 loci. UCB recipients were younger, weighed less, more likely to have advanced leukemia and received a lower dose of nucleated cells.

Bone Marrow Transplantation for Leukaemia – Current Status and Strategies for Improvement

Over the last 35 years, bone marrow transplantation (BMT) has evolved from a highly experimental therapy to a well-established treatment used in the management of tens of thousands of patients annually. The International Bone Marrow Transplant Registry (IBMTR) estimated that approximately 17,000 allogeneic and 30,000 autologous transplants were performed in 2003.1 Despite its widespread use, marrow transplantation is unavailable to some patients because of the lack of an appropriate source of stem cells, and in many others the treatment fails because of excessive toxicity or an inability to eradicate the disease for which it is being used. The following discussion will briefly review the current status of BMT in the treatment of leukaemia and will discuss some strategies being pursued to improve the technique.

Differences in characteristics of United States hematopoietic stem cell transplant (HSCT) centers by proportion of ethnic minorities

6028 Background: The International Bone Marrow Transplant Registry has reported higher mortality in Hispanics with leukemia and received HLA-identical sibling transplantation when compared to whites. It is unknown if transplant center characteristics can partially explain this disparity. We hypothesize that transplant centers do not systematically differ according to the proportion of minorities transplanted. We compared the characteristics of transplant centers that perform a higher proportion of minorities to centers performing transplants to a predominantly white population. Methods: We obtained center characteristics on 116 U.S. transplant centers performing HLA-identical sibling transplantation and compared the following: physician and other health care provider; transplant unit procedure and resources; and, medical center organization according to the volume percentage of minorities transplanted (high ≥ 20% vs. low< 20 %) and percentage of Hispanics transplanted (high ≥10% vs. low <10 %). Results: Centers transplanting a higher proportion of minorities were more likely to perform fewer transplants/year (40 v 66, p<.01), have fewer devoted transplant beds (10 v 13, p<.05), more likely to be in an urban setting (93% v 73%, p<.01), have lower physician to patient ratio (1:13 v 1:16, p<.03), and were more likely to follow survivors after a year after transplantation (83% v 66%, p<.03). Centers transplanting a higher proportion of Hispanics were also more likely to perform fewer transplants/year (36 v 62, p<.02), have fewer devoted transplant beds (7 v 12, p<.001), less likely to be transplanted in centers performing outpatient transplants (25% vs 56%, p<.005), more likely to be in urban setting (96% v 77%, p<.02), and less likely to have a post-transplant immunization protocol (61% v 83%, p<.01). Conclusions: Center characteristics appear to differ according to the proportion of minorities transplanted; further studies should address the association of these characteristics and it's impact on mortality No significant financial relationships to disclose.

Differences in characteristics of United States hematopoietic stem cell transplant (HSCT) centers by proportion of ethnic minorities

6028 Background: The International Bone Marrow Transplant Registry has reported higher mortality in Hispanics with leukemia and received HLA-identical sibling transplantation when compared to whites. It is unknown if transplant center characteristics can partially explain this disparity. We hypothesize that transplant centers do not systematically differ according to the proportion of minorities transplanted. We compared the characteristics of transplant centers that perform a higher proportion of minorities to centers performing transplants to a predominantly white population. Methods: We obtained center characteristics on 116 U.S. transplant centers performing HLA-identical sibling transplantation and compared the following: physician and other health care provider; transplant unit procedure and resources; and, medical center organization according to the volume percentage of minorities transplanted (high ≥ 20% vs. low< 20 %) and percentage of Hispanics transplanted (high ≥10% vs. low <10 %). Results: C...

Validation and extension of the EBMT Risk Score for patients with chronic myeloid leukaemia (CML) receiving allogeneic haematopoietic stem cell transplants

The European Group for Blood and Marrow Transplantation (EBMT) devised a scoring system to predict survival after allogeneic haematopoietic stem cell transplantation (HSCT) for chronic myeloid leukaemia (CML). The present International Bone Marrow Transplant Registry study of 3211 patients tested the EBMT Risk Score in a independent population, investigated the value of adding other variables, evaluated a new risk score specifically for chronic phase and compared the allograft risk scores with risk scores established by Sokal in 1984 and Hasford in 1998 for survival with non-transplant treatments. The primary outcome was 5-year survival after HSCT; survival curves, regression models and measurements of explained variation were used to compare scores. Using the EBMT scoring system, survival in the independent dataset was almost identical to those in the original EBMT publication, thus validating the EBMT Risk Score. Adding one extra variable, performance status, or designing a score specifically for early chronic phase by using the original five variables with different breakpoints gave results only slightly better than the original EBMT Score. Sokal and Hasford Scores did not predict survival after HSCT. We concluded that the EBMT Risk Score does not currently require modification.

Hydroxychloroquine for the prevention of acute graft-versus-host disease after unrelated donor transplantation

Hydroxychloroquine (HCQ) is an immunosuppressive agent that interferes with antigen presentation and with activity against graft-versus-host disease (GVHD). In a phase II trial assessing the GVHD prophylactic effects of HCQ, 51 consecutive unrelated donor transplant recipients received HCQ in addition to cyclosporin A, methylprednisolone, and methotrexate. HCQ was initiated on pretransplantation day −21 at 800 mg/d and continued until day +100 after transplantation. HCQ was extremely well tolerated and was not associated with side effects. Pharmacokinetic analyses demonstrated large inter- and intrapatient variability. The addition of HCQ did not affect posttransplantation immune recovery. Grade II to IV acute GVHD was observed in 56% of patients, and grade III and IV GVHD was observed in 17%. Day +100 mortality was 22%. When compared with a matched cohort of patients reported to the International Bone Marrow Transplant Registry, patients receiving HCQ had comparable cumulative incidences of grade II to IV acute GVHD. However, lower incidences of grades III and IV GVHD and better GVHD-free survival were observed in HCQ-treated patients ( P = .01). We conclude that prophylactic HCQ is well tolerated and associated with a low incidence of severe acute GVHD. An ongoing placebo-controlled randomized trial will further determine what role HCQ plays in preventing GVHD after allografting.

Syngeneic Hematopoietic Stem-Cell Transplantation for Non-Hodgkin’s Lymphoma: A Comparison With Allogeneic and Autologous Transplantation—The Lymphoma Working Committee of the International Bone Marrow Transplant Registry and the European Group for Blood and Marrow Transplantation

To compare results of syngeneic, allogeneic, and autologous hematopoietic stem-cell transplantation for non-Hodgkin's lymphoma (NHL). The databases of the International Bone Marrow Transplant Registry (IBMTR) and the European Group for Blood and Marrow Transplantation were used to identify 89 NHL patients who received syngeneic transplants. These patients were compared with NHL patients identified from the IBMTR and the Autologous Blood and Marrow Transplant Registry who received allogeneic (T-cell depleted and T-cell replete) and autologous (purged and unpurged) transplants. No significant differences in relapse rates were observed when results of allogeneic transplantation were compared with syngeneic transplantation for any histology. T-cell depletion of allografts was not associated with a higher relapse risk, but was associated with improved overall survival for patients with low-grade and intermediate-grade histology. Patients who received unpurged autografts for low-grade NHL had a five-fold (P =.008) greater risk of relapse than recipients of syngeneic transplants, and recipients of unpurged autografts had a two-fold (P =.0009) greater relapse risk than patients who received purged autografts. Among low-grade NHL patients, the use of purging was associated with significantly better disease-free survival (P =.003) and overall survival (P =.04) when compared with patients who received unpurged autografts. These analyses failed to find evidence of a graft-versus-lymphoma effect, but do provide indirect evidence to support the hypothesis that tumor contamination may contribute to lymphoma relapse, and that purging may be beneficial for patients undergoing autologous hematopoietic stem-cell transplantation for low-grade NHL.

Trends in survival rates after allogeneic hematopoietic stem-cell transplantation for acute and chronic leukemia by ethnicity in the United States and Canada.

Differences in survival among ethnic groups in the United States are reported in numerous diseases and treatment strategies. Whether survival after allogeneic hematopoietic stem-cell transplantation (HSCT) differs by ethnicity is uncertain. Patients (n = 6443) receiving HLA-identical sibling HSCT for acute or chronic leukemia in the United States or Canada between 1985 and 1999 and reported to the International Bone Marrow Transplant Registry were included. The survival of recipients reported as white, black, Hispanic, or Asian was compared using Cox proportional hazards regression adjusting for other clinical factors. Three 5-year periods were studied to evaluate changes over time. Hispanics compared with whites had lower 1-year (53% v 65%; P <.001) and 3-year adjusted survival rates (38% v 53%; P <.001) between 1995 and 1999, the most recent period studied. We failed to find significant differences in survival rates comparing whites with blacks or with Asians in any of the time periods. Overall survival for the entire cohort improved over time, from 56% to 63% at 1 year and from 43% to 51% at 3 years, with greater improvements noted among blacks (45% to 61% at 1 year and 34% to 48% at 3 years). Disparities remain in survival rates between whites and Hispanics despite adjustment for clinical factors. Factors not accounted for in this analysis, such as comorbid disease, socioeconomic status, healthcare access and delivery, and psychosocial and cultural variables, require further prospective study.

Performance of a new clinical grading system for chronic graft-versus-host disease: a multicenter study

AbstractWe recently reported 3 risk factors (RFs) at diagnosis of chronic graft-versus-host disease (cGVHD) that were significantly associated with increased nonrelapse mortality. These included extensive skin involvement (ESI), thrombocytopenia (TP), and progressive type of onset (PTO). The hazard ratio (HR) for mortality of the patients with prognostic score (PS) between 0 and 2 (intermediate-risk; 1 RF) compared to those with PS 0 (favorable-risk; 0 RF) was 3.7 (95% CI, 1.4, 9.3); the HR for patients with PS equal to or more than 2 (high-risk; > 1 RF) compared with intermediate-risk group was 6.9 (3.8, 12.4). A rare presentation of TP and PTO without ESI yielded a PS of 1.8 (intermediate-risk). This paper reports the performance of the prognostic model and the individual RFs using data from an additional 1105 patients from University of Nebraska (n = 60), International Bone Marrow Transplantation Registry (n = 708), Fred Hutchinson Cancer Research Center (n = 188), and University of Minnesota (n = 149). The extent of skin involvement was quantified in 3 cohorts using the available data collected in different formats before the analysis. Although the HR for mortality of the patients in the intermediate-risk group versus those in the favorable-risk group ranged from 2.3 to 8.9 across the centers, it was between 1.6 to 6.9 for patients in the high-risk group versus those in the intermediate-risk group. Although TP itself was uniformly associated with increased risk of mortality across all test samples, ESI and PTO showed statistically significant associations with mortality in 1 and 2 cohorts, respectively. In conclusion, the model was predictive of cGVHD-specific survival, but the mortality hazard associated with ESI was lower in each of these test samples compared with the learning sample. Although the new clinical grading based on the model is promising because of its utility across multiple independent data sets, prospective validation is needed.

Decreased treatment failure in recipients of HLA-identical bone marrow or peripheral blood stem cell transplants with high CD34 cell doses.

We studied the association between CD34 cell dose and transplant outcomes in 359 bone marrow (BM) and 511 peripheral blood stem cell (PBSC) transplant recipients from human leucocyte antigen (HLA)-identical siblings, reported to the International Bone Marrow Transplant Registry (IBMTR). Transplants for leukaemia were performed between 1995 and 1998. Patients were divided into those receiving below or above the median CD34+ dose, for BM (3 x 106/kg) and PBSC (6 x 106/kg) grafts respectively. Cox proportional hazards regression was used to adjust for baseline patient-, disease- and transplant-related characteristics. Analysis of the BM recipients showed that high CD34 cell dose was associated with lower transplant-related mortality [relative risk (RR) = 0.60, P = 0.033] and treatment failure (inverse of leukaemia-free survival, RR = 0.69, P = 0.032). Among PBSC recipients, high CD34 dose was associated with faster recovery of neutrophils to > 0.5 x 109/l (RR = 1.38, P < 0.001) and platelets to > 20 x 109/l (RR = 1.34, P = 0.003), lower risk of relapse (RR = 0.62, P = 0.029) and treatment failure (RR = 0.74, P = 0.03). We conclude that higher CD34 cell doses decrease treatment failure in recipients of HLA-identical sibling BM and PBSC transplants.

A comparison of allogeneic and autologous bone marrow transplantation for lymphoblastic lymphoma

Lymphoblastic lymphoma (LBL) is a rare, clinically aggressive neoplasm of the young that frequently involves the bone marrow (BM) and/or central nervous system. Because LBL is similar to acute lymphoblastic leukemia, some centers prefer allogeneic hematopoietic stem cell (SC) transplantation to autologous SC transplantation. We retrospectively analyzed outcomes for patients who underwent autologous (auto, n = 128) or HLA-identical sibling (allo, n = 76) SC transplantations from 1989 to 1998 and were reported to International Bone Marrow Transplant Registry (IBMTR) or Autologous Blood and Marrow Transplant Registry (ABMTR). Allo stem cell transplant (SCT) recipients had higher treatment-related mortality (TRM) at 6 months (18% versus 3%, P =.002), and this disadvantage persisted at 1 and 5 years. Early relapse rates after alloSC transplantation and autoSC transplantation were similar, but significantly lower relapse rates were observed in alloSCT recipients at 1 and 5 years (32% versus 46%, P =.05; and 34% versus 56%, P =.004, respectively). No differences were noted in lymphoma-free survival rates between alloSC transplantations and autoSC transplantations (5-year rates 36% versus 39%, P =.82). AutoSCT recipients had higher overall survival at 6 months (75% versus 59%, P =.01), but survival did not significantly differ between the 2 groups at 1 and 5 years (60% versus 49%, P =.09; 44% versus 39%, P =.47, respectively). Multivariate analyses to account for confounding factors confirmed these results. Independent of SCT type, BM involvement at the time of transplantation and disease status more advanced than first complete remission were associated with inferior outcomes. In summary, alloSC transplantation for LBL is associated with fewer relapses than with autoSC transplantation, but higher TRM offsets any potential survival benefit.

Access to stem cell transplantation: do women fare as well as men?

Women have less access to certain types of expensive treatments including renal transplantation, cardiac catheterization and diagnostic studies for lung cancer. Whether women have less access to stem cell transplantation (SCT) is not known. We evaluated allogeneic SCT data from the International Bone Marrow Transplant Registry (IBMTR) and compared them with disease incidence data from the Surveillance and Epidemiologic End Results (SEER) database. We estimated the ratio of males to females among transplanted patients with acute lymphoblastic (ALL), acute myelogenous (AML) and chronic myelogenous (CML) leukemia, diseases for which SCT is often done and compared them to male/female ratios of disease incidence. The association between gender and SCT was estimated as odds ratios (OR) with 95% confidence intervals (CI). There was no association between gender (male vs female) and the rates of SCT for individuals with AML (OR = 0.95, 95% CI = 0.89-1.02), or CML (OR = 1.0; CI = 0.90-1.1). Among patients with newly diagnosed ALL, more males underwent SCT than females (OR = 1.30, CI = 1.18-1.44). Because children with newly diagnosed ALL usually have a favorable prognosis, SCT is not generally a frontline therapy. Therefore, when we compared SCT rates to a population of children with relapsed ALL, the gender differences disappeared (OR = 1.09, CI = 0.94-1.25). We conclude that for the diagnoses where SCT is commonly used, there is no significant bias towards use in males compared to females. While boys with ALL appear to receive SCT at a higher rate, this difference is likely attributable to biological rather than social reasons.

The role of mini-allotransplants in the treatment of solid tumors

Allogeneic stem cell transplantations (SCTs) have been inclinical use for several decades. First they were used astreatment following nuclear accidents, subsequently the mainapplication became the treatment of patients with leukemiafollowed by other hematological malignant diseases [1].Based on many clinical studies and supported by much datafrom transplant registries like the International Bone MarrowTransplant Registry (IBMTR) and the European Group forBlood and Marrow Transplantation (EBMT) it is now clearthat using allogeneic SCTs (using stem cells from a donor) cancure many patients with hematological malignancies [1–4].This is even the case in patients where other treatment modal-ities are not curative [5].Using HLA identical sibling donors, 6-year survival inpatients with acute or chronic myeloid leukemia is about 60%.In patients with acute lymphocytic leukemia it is about 50%and in myelodysplastic syndromes about 55% (refractoryanemia with or without ringsideroblasts) and about 30%for patients with RAEB (refractory anemia with excess ofblast) and RAEB-T (RAEB in transformation) subtypes (dataIBMTR).Also in patients with aplastic anemia [1, 2, 6] and low gradenon-Hodgkin’s lymphoma [7, 8] allogeneic transplantationmay be curative. In patients with multiple myeloma the poten-tial for cure is less clear [9].Although cure can be achieved using allogeneic trans-plantation, the major drawback of this procedure is itstreatment-related mortality due to the high-dose therapy andan immunological anti-host effect [10]. However, there is nowmuch evidence that this immunological anti-host effect alsoimplies an immunological anti-tumor effect [5, 10–12].

HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome

The extent and importance of autoimmune mechanisms in myelodysplastic syndrome (MDS) and the role of immunosuppression in the treatment of this disease are not well defined. We report overrepresentation of HLA-DR2 and its serologic split HLA-DR15 in both MDS and aplastic anemia (AA). Four clinically and ethnically defined patient groups were analyzed. The HLA-DR15 antigen frequencies among North American white MDS patients (n = 72) and AA patients (n = 59), who received immunosuppressive treatment at the National Institutes of Health (NIH), were 36% and 42%, respectively. These antigen frequencies were significantly higher than that of the control population of 240 North American white NIH blood donors typed for HLA antigens by the same molecular technique (HLA-DR15, 21.3%, P =.01 for MDS, P <.001 for AA). Among North American white patients reported in the International Bone Marrow Transplant Registry (IBMTR), 30% of 341 MDS patients and 33% of 364 AA patients were positive for HLA-DR2. These antigen frequencies were higher than those reported for the general North American white population (HLA-DR2, 25.3%, P =.089 for MDS, P =.01 for AA). The DR15 and DR2 frequencies were significantly increased in MDS refractory anemia (RA) (P =.036 and P =.01, respectively) but not MDS refractory anemia with excess blasts. In the NIH MDS patients, HLA-DR15 was significantly associated with a clinically relevant response to antithymocyte globulin (ATG) or cyclosporine immunosuppression (multivariate analysis, P =.008). In MDS with RA, DR15 may be useful as a guide to pathophysiology, prognosis, and treatment.