ESO-ESMO fifth international consensus guidelines for breast cancer in young women (BCY5).

We dedicate this manuscript in memory of a dear friend and colleague Bella Kaufman. The fifth International Consensus Symposium for Breast Cancer in Young Women (BCY5) took place virtually in October 2020, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY4 with incorporation of new evidence to inform the guidelines. Areas of research priorities as well as specificities in different geographic and minority populations were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

Survival of women with inflammatory breast cancer: a large population-based study.

BACKGROUND: Our group has previously reported that women with inflammatory breast cancer (IBC) continue to have worse outcome compared with those with non-IBC. We undertook this population-based study to see if there have been improvements in survival among women with stage III IBC, over time. PATIENT AND METHODS: We searched the Surveillance, Epidemiology and End Results Registry to identify female patients diagnosed with stage III IBC between 1990 and 2010. Patients were divided into four groups according to year of diagnosis: 1990-1995, 1996-2000, 2001-2005, and 2006-2010. Breast cancer-specific survival (BCSS) was estimated using the Kaplan-Meier method and compared across groups using the log-rank test. Cox models were then fit to determine the association of year of diagnosis and BCSS after adjusting for patient and tumor characteristics. RESULTS: A total of 7679 patients with IBC were identified of whom 1084 patients (14.1%) were diagnosed between 1990 and 1995, 1614 patients (21.0%) between 1996 and 2000, 2683 patients (34.9%) between 2001 and 2005, and 2298 patients (29.9%) between 2006 and 2010. The 2-year BCSS for the whole cohort was 71%. Two-year BCSS were 62%, 67%, 72%, and 76% for patients diagnosed between 1990-1995, 1996-2000, 2001-2005, and 2006-2010, respectively (P < 0.0001). In the multivariable analysis, increasing year of diagnosis (modeled as a continuous variable) was associated with decreasing risks of death from breast cancer (HR = 0.98, 95% confidence interval 0.97-0.99, P < 0.0001). CONCLUSION: There has been a significant improvement in survival of patients diagnosed with IBC over a two-decade time span in this large population-based study. This suggests that therapeutic strategies researched and evolved in the context of non-IBC have also had a positive impact in women with IBC.

UK Cancer Healthcare Professionals Collaborating With Colleagues in Low- and Middle-Income Countries: Mapping the Extent and Nature of Partnerships; Future Implications.

AIMS: In 2020 the UK Global Cancer Network (UKGCN) was formed to unite those in the UK interested in Global Oncology and to strengthen collaborative partnerships with stakeholders working across low- and middle-income countries (LMICs) in cancer health systems, governance, and care. The UKGCN undertook a mapping exercise to document collaborations to inform the UK's global oncology strategy. MATERIALS AND METHODS: A semi-structured survey was developed and disseminated using a snowball method over ten weeks from February 2021 across the UK's cancer community, to identify individuals and institutions engaged in clinical practice, research, and/or education with partners in LMICs. The survey was sent to individuals in NHS hospitals, charities, universities, other organisations, UKGCN members, and to contacts identified by a literature and web search. RESULTS: A total of 639 invitations were sent, and 88 responses were received. Results demonstrate a range of collaborative efforts spanning many areas of cancer control: health promotion, prevention, diagnosis and treatment, survivorship, and palliative care. A wide range of countries were represented from Sub-Saharan Africa, South America, the MENA region, China, and South-East Asia. The projects included education and training (146), clinical practice/care (144), and research (226). CONCLUSION: This mapping exercise demonstrated considerable UK collaboration with stakeholders in LMICs across all three domains of education, clinical care, and research. The survey results provide an initial framework from which to promote in-depth strategic intelligence on the broad range of activities undertaken by the UK global oncology community. This information has been used as a catalyst to create new partnerships and connect colleagues working in similar geographical settings, encouraging bidirectional learning. The UKGCN will galvanise endeavours to improve equitable access to cancer services globally.

Beyond Teenage and Young Adult Cancer Care: Care Experiences of Patients Aged 25-39 Years Old in the UK National Health Service.

AIMS: Adolescents and young adults aged 15-39 years with cancer face unique medical, practical and psychosocial issues. In the UK, principal treatment centres and programmes have been designed to care for teenage and young adult patients aged 13-24 years in an age-appropriate manner. However, for young adults (YAs) aged 25-39 years with cancer, little access to age-specific support is available. The aim of this study was to examine this possible gap by qualitatively exploring YA care experiences, involving patients as research partners in the analysis to ensure robust results. MATERIALS AND METHODS: We conducted a phenomenological qualitative study with YAs diagnosed with any cancer type between ages 25 and 39 years old in the last 5 years. Participants took part in interviews or focus groups and data were analysed using inductive thematic analysis. Results were shaped in an iterative process with the initial coders and four YA patients who did not participate in the study to improve the rigor of the results. RESULTS: Sixty-five YAs with a range of tumour types participated. We identified seven themes and 13 subthemes. YAs found navigating the healthcare system difficult and commonly experienced prolonged diagnostic pathways. Participants felt under-informed about clinical details and the long-term implications of side-effects on daily life. YAs found online resources overwhelming but also a source of information and treatment support. Some patients regretted not discussing fertility before cancer treatment or felt uninformed or rushed when making fertility preservation decisions. A lack of age-tailored content or age-specific groups deterred YAs from accessing psychological support and rehabilitation services. CONCLUSIONS: YAs with cancer may miss some benefits provided to teenagers and young adults in age-tailored cancer services. Improving services for YAs in adult settings should focus on provision of age-specific information and access to existing relevant support.

Lymphocyte-predominant Hodgkin lymphoma--clinical features and treatment outcomes from a 30-year experience.

BACKGROUND: Lymphocyte-predominant Hodgkin disease (LPHD) is a rare subtype of Hodgkin lymphoma, for which there is limited evidence regarding the presentation, natural history and treatment outcomes. PATIENTS AND METHODS: We conducted a single-institution retrospective review all of patients diagnosed with LPHD over a 30-year period. RESULTS: Eighty-eight patients were included. Median follow-up was 13 years. Local radiotherapy or chemoradiotherapy resulted in durable disease control in patients with stage I or II disease. Advanced stage at presentation, presence of B symptoms, low albumin, and either partial response or stable disease to first treatment were associated with worse treatment outcomes. Relapse rate for the entire cohort was 44%, with an 8% rate of transformation to large-cell lymphoma. Rituximab in combination with chemotherapy resulted in durable remission in a heavily pretreated subgroup. Outcomes with autologous transplant are discussed. CONCLUSION: Our series has the longest follow-up of any report, includes the only series of patients treated with autologous transplant, and has the largest group of patients treated with rituximab and chemotherapy in this indication.

A randomised comparative trial of infusional ECisF versus conventional FEC as adjuvant chemotherapy in early breast cancer: the TRAFIC trial.

BACKGROUND: The epirubicin with cisplatin and infusional 5-fluorouracil (5-FU) (ECisF) regimen was found to be highly active in the treatment of metastatic breast cancer and as neoadjuvant therapy. The UK TRAFIC (trial of adjuvant 5-FU infusional chemotherapy) trial (CRUK/95/007) compared this schedule with 5-FU, epirubicin and cyclophosphamide (FEC60) as adjuvant therapy in patients with early breast cancer. METHODS: In this multicentre, open-label, phase III randomised controlled trial, 349 women were randomly assigned to receive i.v. ECisF [epirubicin 60 mg/m(2), day 1, cisplatin 60 mg/m(2), day 1 and 5-FU 200 mg/m(2) by daily 24-h infusion (n = 172)] or FEC [5-FU 600 mg/m(2), day 1, epirubicin 60 mg/m(2), day 1 and cyclophosphamide 600 mg/m(2), day 1 (n = 177)]. Both treatments were delivered every 3 weeks for six cycles. The primary end point was relapse-free interval (RFI). TRAFIC is registered as an International Standard Randomised Controlled Trial (ISRCTN 83324925). RESULTS: All randomised patients were included in the intent-to-treat population. With a median follow-up of 112 months, there was no significant difference in RFI between the treatment groups [hazard ratio 0.84 (95% confidence interval 0.60-1.19); P = 0.33]. Toxic effects were more frequent in patients allocated to ECisF. CONCLUSIONS: While limited by size, TRAFIC has long follow-up. No evidence of a clinically worthwhile benefit for the infusional treatment compared with standard treatment was observed which would justify further investigation or widespread use.

Two different first-line 5-fluorouracil regimens with or without oxaliplatin in patients with metastatic colorectal cancer.

BACKGROUND: Oxaliplatin, 5-fluorouracil (5-FU), and leucovorin (LV) are standard first-line treatments for patients with metastatic colorectal cancer (mCRC). The aim of this multicentre, open-label, phase IIIb study was to assess the addition of oxaliplatin to two different 5-FU regimens. PATIENTS AND METHODS: Patients with previously untreated mCRC were randomised to arm A [two-weekly oxaliplatin 85 mg/m(2) + either continuous intravenous infusion (CIV) of 5-FU without LV or two-weekly bolus and CIV 5-FU + LV (LV5FU2)] or arm B (5-FU CIV or LV5FU2 alone). Irinotecan monotherapy was planned on progression. RESULTS: A total of 725 patients were enrolled. After a fixed follow-up of 2 years for each patient, 2-year survival rates were 27.3% and 24.8% in arms A and B, respectively (hazard ratio 0.93; 95% confidence interval 0.78-1.10). The addition of oxaliplatin significantly improved response rates (54.1 versus 29.8%; P < 0.0001) and median progression-free survival (7.9 versus 5.9 months; P < 0.0001). The most common grade 3-4 toxic effects were neutropenia (arm A, 33%; arm B, 5%), diarrhoea (arm A, 14%; arm B, 8%), and fatigue (arm A, 9%; arm B, 8%). CONCLUSIONS: Despite improved rates of tumour control, these results failed to demonstrate a survival benefit from the addition of oxaliplatin to infused 5-FU and lend further support to the use of sequential monotherapy in some patients with mCRC.

Platinum-based chemotherapy in triple-negative breast cancer.

BACKGROUND: Experimental data suggest that triple-negative (TN) breast cancer may have increased sensitivity to platinum-based chemotherapy but clinical data are limited. We present our long-term results with platinum-based chemotherapy for TN breast cancer. PATIENTS AND METHODS: In all, 94 (17 TN), 79 (11 TN) and 155 (34 TN) patients receiving platinum-based chemotherapy in neo-adjuvant/adjuvant and advanced setting were included. Response rates and outcome were compared for TN tumours versus others. RESULTS: Neo-adjuvant complete response rates were significantly higher for TN tumours (88%) than others (51%; P = 0.005). The 5-year overall survival (OS) for TN tumours following adjuvant/neo-adjuvant chemotherapy was 64% [95% confidence interval (CI) 44% to 79%] compared with 85% (95% CI 79% to 90%) for others. Five-year disease-free survival for TN tumours was 57% (95% CI 37% to 73%) compared with 72% (95% CI 64% to 78%) for others. For patients with advanced breast cancer, overall response rates were 41% for TN tumours and 31% for others (P = 0.3). Patients with TN tumours had a significantly prolonged progression-free survival of 6 months compared with 4 months for others (P = 0.05), though the OS was not significantly different between the two groups (11 versus 7 months). CONCLUSION: Platinum-based chemotherapy achieves increased response rates for TN tumours, with a trend towards worse survival in early breast cancer through an improved survival in advanced disease. Prospective randomised trials are warranted.

Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma.

BACKGROUND: The purpose of this study was to assess prognostic factors and outcome of patients with relapsed/refractory Hodgkin's lymphoma (HL) who received high-dose chemotherapy and autologous stem-cell transplant (ASCT). PATIENTS AND METHODS: Data on 195 patients who received ASCT between 1985 and June 2005 were reviewed. Median time from first treatment to ASCT was 2.6 years (0.4-27.3). Demography at ASCT was 61% stage IV, median age 31 years (18-69), median prior treatment (tx) regimens 3 (2-7), median Hasenclever index 3 (0-6); 150 patients had responding disease [54 complete remission (CR), 96 partial remission (PR)], and 45 patients had untested relapse/refractory disease. RESULTS: Post-ASCT, 61% (119/195) patients attained CR with an overall response (CR + PR) of 85%. Twelve patients had nonrelapse mortality. Of 119 patients attaining CR, 27 relapsed: 3 after attaining CR for >5 years and 1 after attaining CR for >10 years. Median overall survival (OS)/progression-free survival (PFS) from ASCT was 9 years/2.9 years. Five-year OS/PFS was 55% of 44% and 10-year OS/PFS was 49.4% of 37% for whole group. Twenty (10%) patients developed second cancer (seven secondary acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS)). Probability of developing second cancer at 10 years was 14.7% (95% confidence interval 8.9% to 23.8%) and 24.8% at 19 years. CONCLUSION: These data provide the longest follow-up reported for patients receiving ASCT for relapsed/refractory HL. In addition to previously described prognostic factors, our data show that Hasenclever index <3 influences outcome favorably and attaining CR at ASCT leads to a better outcome.

The role of maintenance chemotherapy after autotransplantation for acute lymphoblastic leukemia in first remission: single-center experience of 100 patients.

A total of 100 adults with ALL in first CR received melphalan (110 mg/m(2)) with TBI followed by autologous marrow (n=35) or single-agent melphalan (200 mg/m(2)) followed by autologous blood stem cells (n=65). After adequate hematologic recovery, maintenance chemotherapy with 6-mercaptopurine, methotrexate and vincristine-prednisone was administered for 2 years. Six patients, all TBI recipients (P=0.001), died of toxicity. In total 70 patients received 6-mercaptopurine, 53 received methotrexate and 40 received vincristine-prednisone. The cumulative incidence of relapse at 7 years was 45%. The 7-year probabilities of disease-free survival (DFS) and overall survival were 45 and 48%. Age 30 years, >4 weeks to attain remission, and karyotypes t(4;11) and t(9;22) were associated with adverse outcome. Patients with 0 (standard risk), 1 (intermediate risk), and 2-3 (high risk) adverse features had 7-year cumulative incidences of relapse of 19, 53 and 82% (P<0.0001), and 7-year DFS probabilities of 73, 36 and 7% (P<0.0001). The 7-year probabilities of DFS for patients receiving 0, 1, 2 and 3 maintenance chemotherapy agents were 15, 29, 58 and 61% (P<0.0001). Maintenance chemotherapy intensity was an independent determinant of outcome in Cox analysis. Maintenance chemotherapy after autotransplantation reduces relapse and improves outcome in adult patients with ALL.

Future challenges.

Treatment for patients with myeloma has changed unrecognisably over the last two decades and now includes a sequence of treatments including chemotherapy, biological targeted therapy with or without consideration for high-dose therapy (autologous and allogeneic stem cell transplantation for younger and fit patients). As patients can now expect a doubling of median survival and a 20-30% chance of surviving longer than 10 years, the focus of treatment is shifting to long-term quality of life. This article focuses on future challenges facing clinicians treating myeloma and how best we may optimize our resources.

The evolving background for high-dose treatment for myeloma.

In the constantly evolving field of myeloma, this special issue is slanted towards how the newer targeted treatments fit in with various transplantation strategies. High-dose treatment for myeloma with autologous stem cell transplantation started 25 years ago, with the consequence of producing complete remissions and a doubling of survival. Since then, its role has been refined and it has been accepted as standard treatment. The current challenge is to optimize its use into a background of the development, availability and regulatory approval of newer targeted therapies such as Thalidomide, Revlimid (Lenalidomide) and Velcade (Bortezomib). This special issue addresses these problems, and gives particular emphasis on the attainment of very long-term survival, with normal quality of life for patients with myeloma who do not necessarily need to be cured of their molecular disease, that is, they are 'operationally cured.' It is hoped that the reader will find the information in this issue useful in the day-to-day management of patients and we hope that this will also inspire new research directions designed to improve the outcome of patients with myeloma.

Use of physiological doses of human growth hormone in haematological patients receiving intensive chemotherapy promotes haematopoietic recovery: a double-blind randomized, placebo-controlled study.

In vivo and in vitro studies suggest human growth hormone (hGH) receptors on bone marrow stem cells may be biologically active and could be exploited to promote haemopoetic recovery after intensive chemotherapy. Patients with haematological malignancies receiving intensive chemotherapy and requiring hospitalization were randomized in a double-blind, placebo-controlled single-centre trial. Patients were randomly assigned to receive either hGH 500 microg/day or placebo, for 6 weeks. There was no significant difference in patient characteristics at baseline between the placebo and treatment arms. Patients treated with hGH showed significantly faster recovery of platelets to 25 x 10(9)/l (median of 16 versus 19 days; P = 0.03) compared to the placebo-controlled arm (hazard ratio 1.47 favouring hGH, 95% confidence interval (CI), 1.03-2.08). Time to relapse did not differ significantly between arms. There was no change in the anthropometric parameters at the start and end of hGH/placebo therapy. The study drug was well tolerated. Treatment with hGH in physiological doses improves platelet recovery, but is not associated with a lower relapse rate or improved anthropometric parameters in patients receiving intensive chemotherapy.

A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation.

This open-label, dose-escalation study assessed the maximum tolerated dose (MTD) of the new antifungal micafungin in patients undergoing haematopoietic stem cell transplantation (HSCT). Participants received 3, 4, 6 or 8 mg/kg/day micafungin intravenously from 7 days to a maximum of 28 days or until neutropaenia resolved. The MTD was defined as the highest dose not causing the same Grade 3 or 4 adverse event in three or more patients. All 36 participants received >/=8 days treatment for a median of 18 days (range: 8-28); 1 patient withdrew consent and a further 11 discontinued to receive another systemic antifungal agent for a suspected infection. No case of confirmed invasive fungal infection occurred. Adverse events were those expected for patients undergoing HSCT and showed no evidence of dose-related toxicity. Criteria for MTD were not met; no patient had a Grade 3 or 4 adverse event considered causally related to micafungin. Thus, the MTD of micafungin can be inferred to be 8 mg/kg/day or higher.

An elective single autograft with high-dose melphalan: single-center study of 451 patients.

In all, 451 myeloma patients, 51% previously untreated, underwent elective single autotransplantation after 200 mg/m(2) melphalan between 1985 and 2001 at the Royal Marsden Hospital. The therapy sequence was: Induction (vincristine, doxorubicin, methylprednisolone+/-cyclophosphamide), marrow or filgrastim-mobilized blood stem cell harvest, autograft, and interferon-alpha2b maintenance. A total of 27 (6%) died of transplant-related toxicity, all within 3 months. Complete or near-complete remission was seen in 59% with an overall response rate of 91%. Subsequent disease progression was seen in 285, and 17 died of unrelated causes. In all, 206 patients were alive at the last follow-up, 6 months to 17.7 years post-transplant (median 65 months); 122 without disease progression at 6 months to 17.7 years (median 58 months). The median overall (OS) and event-free (EFS) survivals were 5.9 and 2.4 years, with 10-year OS and EFS probabilities of 31.4 and 16.5%, respectively. In Cox analysis, it was seen that significantly longer OS occurred for patients who had beta-2-microglobulin <3.5 mg/l (P<0.0001), age <60 years (P=0.001) and albumin > or =35 g/l (P=0.009). EFS was also longer if beta-2-microglobulin was <3.5 mg/l (P=0.0056) and patients were <60 years of age (P=0.033). We conclude that with a single planned autograft, patients with myeloma have an excellent outcome.

The impact of donor gender on outcome of allogeneic hematopoietic stem cell transplantation for multiple myeloma: reduced relapse risk in female to male transplants.

The impact of the donor gender on outcome in HLA-identical sibling donor hematopoietic stem cell transplantation for multiple myeloma was studied in a retrospective registry study of 1312 patients (476 male to male (M --> M); 334 female to male (F --> M); 258 male to female (M --> F); 244 female to female (F --> F) reported to the European Group for Blood and Marrow Transplantation (EBMT). The best overall survival (OS) from the time of transplantation was found in F --> F (median 41 months) with no significant difference between other groups (median 25 months in M --> M, 18 months in F --> M, 19 months in M --> F) despite a significantly higher nonrelapse mortality in F --> M. This was due to a significantly lower relapse rate (REL) in F --> M compared to all other groups. Before 1994, OS was poorer in F --> M than in M --> M, which improved to similarity from 1994 onwards (median 29 months in M --> M and 25 months in F --> M). The reduced REL contributed to this improvement in F --> M indicting a gender-specific graft vs myeloma effect. Therefore, a female donor is as good as a male one for male patients, while for female patients gender disparity is a negative factor for outcome.

The management of poor-prognosis, non-seminomatous germ-cell tumours.

Despite a high cure rate in men with testicular cancer, some men in the poor-prognosis group have a less favourable outcome. Poor-prognosis non-seminomatous germ-cell tumours (NSGCT) are defined as those with high tumour markers, non-pulmonary visceral metastases or a mediastinal primary site at presentation. When treated with standard chemotherapy regimens, such as bleomycin, etoposide and cisplatin (BEP), cure rates of less than 50% have been achieved in an international pooled analysis. Some strategies aimed at improving results include the use of multi-agent regimens (e.g. POMB/ACE), intensive-induction chemotherapy (e.g. CBOP/BEP), new chemotherapy drugs, such as ifosfamide, gemcitabine, oxaliplatin, paclitaxel, high-dose chemotherapy, including autotransplantation. To date, no schedule has been proven to be better than standard BEP in randomised trials. We will review the published data relating to first-line and salvage treatment of poor-prognosis NSGCT. To advance the management of this disease, physicians treating poor-prognosis disease are urged to support multi-centre trials, such as the recently launched MRC TE23 study comparing BEP and CBOP/BEP.

Treatment of patients with metastatic pancreatic cancer: Experience from a tertiary Indian cancer center.

BACKGROUND: The aim of this study was to look at the outcome of patients with metastatic pancreatic cancer treated at a tertiary cancer center in India. PATIENTS AND METHODS: A total of 101 patients with locally advanced and metastatic pancreatic cancer diagnosed between May 2012 and July 2013 were identified from a prospectively maintained database at the tertiary cancer center. Overall survival (OS) was computed using the Kaplan-Meir product limit method and compared across groups using the log-rank statistics. Cox proportional hazards model, adjusted for a number of patient and tumor characteristics, was then used to determine factors prognostic for OS. RESULTS: Median age at diagnosis was 55 years (range: 21-81 years). 57.4% (n = 58) of patients were male, 22% (n = 22) had performance status (PS) of <2 at diagnosis and 89% received first-line chemotherapy, while the rest received best supportive care. For the whole cohort, 6 month and 1-year OS was 57% (95% confidence interval [CI]: 46-66%) and 47% (95% CI: 35-57%), respectively. In a multivariable model, PS <2 and oligometastatic disease were associated with a significantly decreased risk of death. CONCLUSION: Results from our analysis indicate that the prognostic outcome among Indian patients with metastatic pancreatic cancer is poor with survival outcomes similar to those reported in North America and Europe.

Some early phase II trials in previously untreated multiple myeloma: The Royal Marsden experience.

Multiple myeloma is at a stage today where acute leukemia was in the 1960s and 1970s when the aim was to attain complete remission (CR), which would translate into prolonged overall survival (OS) and a cure. The Royal Marsden group was the first to establish a dose-response effect for melphalan leading to CR in patients with myeloma. Since then, different strategies have been developed to improve the results of high-dose therapy, including alternating conditioning regimens, peripheral blood stem cells (PBSC) as a source of stem cells, purging techniques to decrease graft contamination by the myeloma cell, increased dose intensity by means of tandem transplants, and finally, allogeneic matched or unmatched stem cell transplantation. Components of treatment offered at Royal Marsden since 1980 are upfront high-dose melphalan (HDM) 140 mg/m(2), induction infusional chemotherapy followed by consolidation with HDM with autotransplantation, and maintenance with interferon-alpha2b (IFN) (collectively termed sequential therapy). Each of these components has shown benefits in selected studies and together they have dramatically improved the outlook for patients with myeloma.

Does donor-recipient ABO incompatibility protect against relapse after allogeneic bone marrow transplantation in first remission acute myeloid leukemia?

It is not known if donor-recipient ABO blood group incompatibility contributes to graft-versus-leukemia after allogeneic BMT. One hundred and nineteen patients with acute myeloid leukemia in first remission underwent non-T cell-depleted marrow allografts from HLA-identical siblings after TBI and cyclophosphamide (n = 72) or melphalan (n = 47). GVHD prophylaxis comprised cyclosporine alone or cyclosporine-methotrexate. Twenty-two patients relapsed at 3-46 months (median 7): 18 of 76 patients with ABO-matched donors and four of 43 patients with ABO-mismatched donors (actuarial 5-year probabilities 33 +/- 6% vs 12 +/- 6%; P = 0.028). The incidence of acute and chronic GVHD was not affected by ABO mismatch. The following factors were studied in Cox analysis for effect on outcome: gender, age, FAB subtype, ABO mismatch, CR-transplant interval, conditioning, TBI dose, nucleated cell dose, lymphocyte recovery, acute GVHD, and chronic GVHD. Donor-recipient ABO match was the only factor independently associated with a higher risk of relapse (RR = 3.7; 95% Cl, 1.1-12.6; P = 0.04). ABO mismatch was also associated with superior overall and disease-free survivals. We conclude that ABO incompatibility may influence relapse rates and survival favorably after allogeneic BMT. It is not known if this holds true for allogeneic blood stem cell transplants.