Disease complexity and economic burden on patients with colon cancer in the SEER-Medicare population.

30 Background: The relatively high cost of cancer care is receiving national attention. Treating cancer includes not only managing this illness, but also the complications and exacerbation of the patients’ underlying comorbid conditions. The purpose of this study was to analyze how the charges for colon cancer care are affected by the complexity of the patients’ underlying health problems. Methods: We searched the Surveillance, Epidemiology, and End Results-Medicare database to identify patients diagnosed with colon cancer from 2009 through 2011. The estimated charges of the patients’ Medicare claims were stratified by survival time, disease stage, patient age, and comorbidity number. We defined patients’ 12 months of care as the 1 month immediately preceding cancer diagnosis plus the 11 months immediately following diagnosis. Results: We identified 10,822 patients newly diagnosed with colon cancer during the study period. Of those patients, one quarter died within 11 months after diagnosis. Treatment for early-stage cancer was significantly less expensive than treatment for advanced disease. For patients with early-stage disease, the charges for surgery, chemotherapy, and/or radiation therapy constituted a smaller contribution to the overall care charges. For patients with advanced-stage disease, the substantially higher overall care charges were largely due to charges for chemotherapy and/or biotherapy. Among patients with the same disease stage at diagnosis (except for patients stage IV disease), those with a survival time of less than 12 months incurred higher charges than those with a survival time of 12 months or more did. Regardless of disease stage, survival time, or age, patients with one and two or more comorbid conditions incurred statistically significant higher charges (7.0% and 29.7%, respectively) than those with no comorbid conditions. Conclusions: These findings demonstrate the important contribution of disease complexity among patients with cancer to the analysis of resource utilization. Using overall cancer care cost or reimbursement models that do not incorporate disease complexity may negatively affect hospitals that care for a high proportion of patients with complex conditions.

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International Study of Primary Mucinous Ovarian Carcinomas Managed at Tertiary Medical Centers

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001263 ◽

2018 ◽

Vol 28 (5) ◽

pp. 915-924 ◽

Cited By ~ 4

Author(s):

Jennifer J. Mueller ◽

Henrik Lajer ◽

Berit Jul Mosgaard ◽

Slim Bach Hamba ◽

Philippe Morice ◽

...

Keyword(s):

Early Stage ◽

Statistical Tests ◽

Stage Iv ◽

Stage I ◽

Stage Iii ◽

Oncologic Outcomes ◽

Disease Stage ◽

Ovarian Carcinomas ◽

Early Stage Disease ◽

Medical Centers

ObjectiveWe sought to describe a large, international cohort of patients diagnosed with primary mucinous ovarian carcinoma (PMOC) across 3 tertiary medical centers to evaluate differences in patient characteristics, surgical/adjuvant treatment strategies, and oncologic outcomes.MethodsThis was a retrospective review spanning 1976–2014. All tumors were centrally reviewed by an expert gynecologic pathologist. Each center used a combination of clinical and histologic criteria to confirm a PMOC diagnosis. Data were abstracted from medical records, and a deidentified dataset was compiled and processed at a single institution. Appropriate statistical tests were performed.ResultsTwo hundred twenty-two patients with PMOC were identified; all had undergone primary surgery. Disease stage distribution was as follows: stage I, 163 patients (74%); stage II, 8 (4%); stage III, 40 (18%); and stage IV, 10 (5%). Ninety-nine (45%) of 219 patients underwent lymphadenectomy; 41 (19%) of 215 underwent fertility-preserving surgery. Of the 145 patients (65%) with available treatment data, 68 (47%) had received chemotherapy—55 (81%) a gynecologic regimen and 13 (19%) a gastrointestinal regimen. The 5-year progression-free survival (PFS) rates were 80% (95% confidence interval [CI], 73%–85%) for patients with stage I to II disease and 17% (95% CI, 8%–29%) for those with stage III to IV disease. The 5-year PFS rate was 73% (95% CI, 50%–86%) for patients who underwent fertility-preserving surgery.ConclusionsMost patients (74%) presented with stage I disease. Nearly 50% were treated with adjuvant chemotherapy using various regimens across institutions. The PFS outcomes were favorable for those with early-stage disease and lower but acceptable for those who underwent fertility preservation.

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Lung Cancer in Homeless People: Clinical Outcomes and Cost Analysis in a Single Institute

Canadian Respiratory Journal ◽

10.1155/2016/3727689 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Koung Jin Suh ◽

Ki Hwan Kim ◽

Jin Lim ◽

Jin Hyun Park ◽

Jin-Soo Kim ◽

...

Keyword(s):

Lung Cancer ◽

Early Stage ◽

Medical Center ◽

Homeless People ◽

Stage Iv ◽

Disease Stage ◽

Curative Surgery ◽

Early Stage Disease ◽

Outpatient Visits

Introduction. To characterize the demographic and clinical features, outcomes, and treatment costs of lung cancer in homeless people. Methods. Medical records of 22 homeless patients with lung cancer at Seoul National University Boramae Medical Center in Seoul, South Korea, were retrospectively analyzed. Results. All patients were men (median age, 62 years). Most patients (78%) had advanced disease (stage IIIB, n=2; stage IV, n=15). Seven died during initial hospitalization (median survival, 1.5 months). Six were lost to follow-up after initial outpatient visits or discharges from initial admission (median follow-up, 13 days). Only 4 received appropriate treatment for their disease and survived for 1, 15, 19, and 28 months, respectively. Conversely, 4 of 5 patients with early stage disease (stage I, n=4; stage IIA, n=1) received curative surgery (median follow-up 25.5 months). The median treatment cost based on 29 days of hospitalization and 2 outpatient visits was $12,513, constituting 47.3% of the 2013 per capita income. Inpatient treatment accounted for 90% of the total costs. The National Health Insurance Service paid 82% of the costs. Conclusion. Among the homeless, lung cancer seems to be associated with poor prognosis and substantial costs during a relatively short follow-up and survival period.

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Expression of the Cancer-Testis Antigens, SEMG 1 and Protamine 1, in Early CLL: Their Relationship to Disease Stage and Zap 70 Expression.

Blood ◽

10.1182/blood.v110.11.4680.4680 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4680-4680

Author(s):

Farouk Meklat ◽

Yana Zhang ◽

Zhiqing Wang ◽

Jian Zhang ◽

Sukhrob Mustalov ◽

...

Keyword(s):

Vaccine Development ◽

Tumor Vaccine ◽

Early Stage ◽

Disease Stage ◽

Early Disease ◽

Early Stage Disease ◽

Stage Disease ◽

Ct Antigen ◽

Cancer Testis ◽

Protamine 1

Abstract Despite advances in modern chemotherapy, CLL remains incurable. CLL is an indolent disease. It expresses a panel of Cancer-Testis (CT) antigens. CLL leukemia cells are susceptible to the cytotoxicity of T cells. CLL is, therefore, an ideal disease for immunotherapeutic approaches. Immunotherapy, in addition to being less toxic and more specific than chemotherapy, provides a different mode of cytotoxicity that may synergize with that induced by chemotherapeutic agents. Immunotherapy also offers the prospect of inducing immune memory that may be important for long term disease-free survival of patients with CLL. However, there are obstacles that may prevent successful immunotherapy. CLL patients are generally immunosuppressed even before any therapy is given and the immunosuppression increases as the disease progresses. Therefore, any immunotherapeutic approaches for CLL should be aplied in early disease when immunosuppression is least encountered. We previously demonstrated the expression of a CT antigen, SEMG 1, in 3/9 patients with CLL. Furthermore, we also demonstrated that the presence of high titer IgG in the serum of patients expressing SEMG 1, suggesting the in vivo immunogenicity of SEMG 1 in the cancer-bearing autologous host. We have also recently used SEMG 1 as the bait in a yeast two-hybrid system of testicular cDNA library and identified that Protamine 1 is the interacting ligand of SEMG 1 and that Protamine 1 is also a novel CT antigen, suggesting that both SEMG 1 and Protamine 1 may be suitable antigens for tumor vaccine development. However, the expression of SEMG 1 and Protamine 1 in early CLL is unknown. We have in this study set out to determine whether or not SEMG 1 and/or Protamine 1 could be used for the design of tumor vaccine for the targeting of patients with early CLL, in particular, those with poor risk disease, as predicted by Zap 70 expression. Using pairs of sequence-specific primers in RT-PCR on a cohort of CLL (41 Stage 0/I and 6 Stage II/III), we found that SEMG 1 gene is expressed in 24/47 (51%) and Protamine 1 in 16/47 (34%) of CLL patients. Gene expression in most cases was associated with the detection by immunocytochemistry of SEMG 1 and/or Protamine 1 in the CLL cells. The expression frequency of SEMG1 and Protamine 1 in CLL did not appear to differ between early and late stage disease. 19/41 of patients with early stage disease and 5/6 of patients with late disease expressed SEMG 1; 12/41 of patients with early stage disease and 4/6 patients with late disease expressed Protamine 1. Furthermore, the expression of these antigens was equally distributed between Zap 70+ and Zap 70− CLL. SEMG 1 was expressed in 4/6 of Zap 70+ CLL (all 6 had early disease) and 2/9 of Zap 70− CLL (1/8 early disease and 1/1 late disease). Interestingly, although Protamine 1 expression in CLL predicted for SEMG 1 co-expression, only 67% of SEMG 1+ CLL expressed Protamine 1. Our results, therefore, suggest that both SEMG 1 and Protamine 1 are suitable targets for tumor vaccine development for some patients with early CLL, especially those with high risk disease, as predicted by Zap 70 expression.

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A Retrospective Analysis of Outcomes of Diffuse Large B Cell Lymphoma (DLBCL) in the Elder Patients in China

Blood ◽

10.1182/blood-2018-99-116641 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5410-5410

Author(s):

Peng Liu ◽

Ying Han ◽

Jianliang Yang ◽

Xiaohui He ◽

Changgong Zhang ◽

...

Keyword(s):

Cell Lymphoma ◽

Early Stage ◽

B Cell Lymphoma ◽

Disease Stage ◽

Early Stage Disease ◽

Large B Cell Lymphoma ◽

Elder Patients ◽

Stage Disease ◽

Ann Arbor ◽

Advanced Disease Stage

Abstract Background: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis compared to the younger population, since older age is associated with comorbidity and suboptimal performance status leading to intolerance of chemo-immunotherapy. The outcome of DLBCL in the older patients (> 60 years) was well described in clinical trials with reported 5-year overall survival (OS) of 50-80% (Coiffier et al., N Engl J Med 2002). Since this group is often precluded from clinical trials and population-based studies are limited, optimal treatment strategy for the old patients with DLBCL remains controversial. Here, we describe a Chinese real-world experience of management of elderly DLBCL patients treated at National Cancer Hospital, China. Methods: This is a single-center, retrospective analysis of consecutive DLBCL patients aged ≥60 who planned to receive chemotherapy +/- rituximab. The standard regimens included 3-4 cycles (early stage disease) or 6 cycles (advanced) of R-CHOP like regimens (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) followed by two rituximab doses in fit patients; R-miniCHOP for unfit and R-CE(etoposide)OP for frail elder patients. Patient data including baseline characteristics, histology, clinical parameters, and treatment outcomes were extracted from hospital medical records. The primary endpoint was progression-free survival (PFS); secondary endpoint was OS. Statistical analyses included descriptive statistics and Kaplan Meier estimates. Results: From June 2006 to December 2012, 349 patients aged ≥60 years were included, in which 204 patients were aged <70 years (Table 1). 326 patients received chemotherapy or chemo-immunotherapy with rituximab. Median follow up was 82 months. Five year PFS and OS of the elder patients were 45.8% and 51.9%, respectively. Significant difference was seen between patients < 70 years and those ≥70 years in terms of PFS (51.0% vs 38.6%, p=0.030) and OS (58.3% vs 42.8%, p=0.007) (Figure 1). Patients with early-stage disease (Ann Arbor StageⅠ/Ⅱ) had better 5-year PFS (60.1% vs 23.5%, p<0.001) and OS (65.3% vs 30.9%, p<0.001) than patients with advanced disease stage (Ann Arbor Stage III/IV) (Figure2). In addition, regimen including rituximab significantly improved the survival than chemotherapy alone (5-year PFS: 37.3% vs 64.0%, p<0.001; 5-year OS: 44.5% vs 69.3%, p<0.001), especially in patients ≥70 years, which almost doubled 5-year PFS and OS (5-year PFS: 25.4% vs 50.7%, p<0.001; 5-year OS: 28.8% vs 56.0%, p<0.001) (Figure3). Conclusions: Elder age (≥70 years) and advanced disease stage (Ann Arbor Stage III/IV) are associated with poor PFS and OS in Chinese elder DLBCL patients. The addition of rituximab significantly improves the survival compared to chemotherapy alone, especially in patients aged ≥70 years. These findings underscore the importance of personalized evaluation and treatment in elder patients with DLBCL. Disclosures No relevant conflicts of interest to declare.

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Recent advances in understanding and managing cutaneous T-cell lymphomas

F1000Research ◽

10.12688/f1000research.21922.1 ◽

2020 ◽

Vol 9 ◽

pp. 331

Author(s):

Patrick M. Brunner ◽

Constanze Jonak ◽

Robert Knobler

Keyword(s):

T Cell ◽

Early Stage ◽

Disease Stage ◽

Treatment Modalities ◽

Early Stage Disease ◽

T Cell Lymphomas ◽

Stage Disease ◽

Related Quality ◽

Health Related ◽

Stage Ivb

Cutaneous T-cell lymphomas (CTCLs) comprise a heterogeneous group of extranodal non-Hodgkin lymphomas involving primarily the skin and mycosis fungoides is its most frequent entity. Whereas most patients show an indolent course in early disease (clinical stages IA to IIA), some patients progress to advanced disease (stage IIB or higher), and the 5-year survival rate is unfavorable: only 47% (stage IIB) to 18% (stage IVB). Except for allogeneic stem cell transplantation, there is currently no cure for CTCL and thus treatment approaches are palliative, focusing on patients’ health-related quality of life. Our aims were to review the current understanding of the pathogenesis of CTCL, such as the shift in overall immune skewing with progressive disease and the challenges of making a timely diagnosis in early-stage disease because of the lack of reliable positive markers for routine diagnostics, and to discuss established and potential treatment modalities such as immunotherapy and novel targeted therapeutics.

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Clear-cell cancer of the ovary—is it chemosensitive?

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200505000-00004 ◽

2005 ◽

Vol 15 (3) ◽

pp. 432-437

Author(s):

S. Pather ◽

M. A. Quinn

Keyword(s):

Clear Cell ◽

Early Stage ◽

Cell Cancer ◽

Stage Iv ◽

Stage I ◽

High Recurrence Rate ◽

Second Line ◽

Early Stage Disease ◽

Chemotherapeutic Regimen ◽

Stage Disease

The records of all patients with clear-cell ovarian cancer (CCC) who underwent complete surgical staging and chemotherapy between 1984 and 2001 were reviewed and 39 patients identified as suitable for study. The mean patient age was 56 years, and the stage distribution was as follows: stage I, 53%; stage II, 13%; stage III, 32%; and stage IV, 2%. One in three patients with stage I disease developed recurrent disease despite adjuvant chemotherapy. Seventy percent of tumors demonstrated a response to combination carboplatin and paclitaxel. Tumors which had either a partial response or failed to respond to first-line chemotherapy demonstrated no response to second-line nonplatinum chemotherapy. Endometriosis was identified in 31% of tumors, and 18% of patients developed deep venous thrombosis (DVT); however, neither endometriosis nor DVT was associated with a poorer outcome. CCC has a high recurrence rate in early-stage disease despite adjuvant treatment with cytotoxic chemotherapy. Advanced disease does respond to carboplatin and paclitaxel, which should be the chemotherapeutic regimen of choice. New second-line agents are urgently required.

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Results of chemotherapy (CT) based protocol for treatment of retinoblastoma (RB)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.9068 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 9068-9068

Author(s):

L. Goyal ◽

S. Banavali ◽

R. Bhagwat ◽

B. Arora ◽

M. Muckaden ◽

...

Keyword(s):

Early Stage ◽

Local Therapy ◽

Stage Iv ◽

Stage I ◽

External Beam Radiation ◽

Patient Treatment ◽

Delayed Presentation ◽

Beam Radiation ◽

Early Stage Disease ◽

Stage Disease

9068 Background: One the main reasons for delayed presentation of children with RB in India is non acceptance of enucleation. CT is being increasingly utilized as primary treatment of RB to reduce the tumor volume and thus avoid enucleation and/or external beam radiation (EBRT) in early stage disease and reduce the risk of relapse in advanced stage disease. Methods: This retrospective (from 1996 to 2001) study involved 62 Patients (pts) (30 were bilateral) who received CT consisting of monthly cycles of carboplatin, etoposide, vincristine and cyclophosphomide. Pts with stage I disease, were started on CT alone, whereas most of the other pts were also started on concurrent EBRT (50Gy). Where indicated, pts also received local therapy, usually cryotherapy & EBRT. Eyes which did not show response or had stable disease, were advised enucleation. Results: Majority of pts had Reese-Ellsworth groups IV-V (74.1%). 17 pts had Stg I, 22 Stg II, 17 Stg III & 6 Stg IV disease (St Jude’s). All pts received CT (median 12 cycles). Out of 92 eyes only 79 were evaluable (13 were already enucleated).The response rate was 73.2% (51.8% CR or near CR); 12.9% had progressive disease. 47 Pts (74%) received RT. Only 23 pts received focal treatment (Cryotherapy 15, laser 3, combination 5). Vision was present in 38 eyes (48.1%) at presentation. 26 eyes (68.4%) were finally saved with useful vision. 20 pts had recurrence. 18 have died (17 died of disease, 1 treatment related sepsis). In those following up in the clinic, survival is 77% for stage I; 78.5% for stage II; 41.6% for stage III. All stage IV pts have died except 1 with nodal disease. Conclusions: CT has a role in the management of RB, however unless it is coupled with good focal therapy the results are poor as shown here. Also longer follow-ups are required because of late recurrences. This data highlights that in developing countries the social reasons complicate patient treatment & compliance. Further efforts are needed to spread awareness of this disease so that patients are diagnosed and treated in earlier stages so as to improve the outcomes. No significant financial relationships to disclose.

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Loss in working years after a breast cancer diagnosis: A population-based study (Sweden).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.5_suppl.209 ◽

2017 ◽

Vol 35 (5_suppl) ◽

pp. 209-209

Author(s):

Mats Lambe ◽

Paul Lambert ◽

Irma Fredriksson ◽

Anna Plym

Keyword(s):

Breast Cancer ◽

Cancer Diagnosis ◽

Early Stage ◽

Stage Iv ◽

Population Level ◽

Breast Cancer Diagnosis ◽

Early Stage Disease ◽

Cancer Data ◽

Stage Disease ◽

Working Age

209 Background: More than half of all women with breast cancer are diagnosed during working age. We present a new measure of clinical and public health relevance to estimate the loss in working years after a breast cancer diagnosis. Methods: Women of working age diagnosed with breast cancer between 1997 and 2012 were identified in the Breast Cancer Data Base Sweden (N = 19,661), together with a breast cancer-free comparison cohort (N = 81,303). Women were followed until permanent exit from the labour market (defined as receipt of disability pension, old-age retirement or death) or censoring. Using flexible parametric survival modelling, the loss in working years was calculated as the difference in the remaining years in the work force between women with and women without breast cancer. Results: The loss in working years was most pronounced in women of younger ages and in women with advanced stage disease. Women aged 50 years at diagnosis with stage I disease lost on average 0.6 years (95% CI, 0.4-0.8) of their remaining working time; the corresponding estimates were 1.2 years (1.0-1.5) in stage II, 3.2 years (2.7-3.7) in stage III, and 8.8 years (7.9-9.8) in stage IV disease. Type of treatment was a clear determinant in women with early stage disease, with a higher loss in working years among women treated with axillary surgery, mastectomy and chemotherapy. Conclusions: Our measure provides a new perspective of the burden of breast cancer in women of working age. The modest loss in working years in women with early stage disease is reassuring, although the economic consequences on a population-level are likely to be high given the large number of women diagnosed with breast cancer every year.

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Outcomes for metastatic colorectal cancer (mCRC) based on microsatellite instability.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.759 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 759-759 ◽

Cited By ~ 4

Author(s):

Timothy Jay Price ◽

Christos Stelios Karapetis ◽

Young Joanne ◽

Amitesh Roy ◽

Rob Padbury ◽

...

Keyword(s):

Microsatellite Instability ◽

Early Stage ◽

Stage Iv ◽

Patient Characteristics ◽

Population Based ◽

Survival Outcomes ◽

Treatment Pathways ◽

Stage Disease ◽

Stage Iv Disease ◽

Population Based Registry

759 Background: Microsatellite instability (MSI) has been associated with improved survival outcomes in early stage CRC. In stage IV disease, MSI represents only 3-5% of cases and currently the prognostic implications are less clear. There is however evolving evidence that treatment pathways should include anti-PD-1 antibodies given the encouraging results in heavily pre-treated MSI mCRC patients. We undertook an analysis of the South Australian mCRC population based registry to explore the relevance of MSI status in this population based registry. Methods: The registry was analysed to assess patient characteristics and survival outcomes comparing patients with MSI or microsatellite stable (MSS) disease. K-M survival analysis was used to assess OS. Results: 4359 patients are registered on the data base. 598 (14%) patients had been tested for MSI. 62 (10.1%) of these patients had demonstrable MSI. Patient characteristics and outcomes are summarized in the table. There are statistically higher rates of right sided primary, poorly differentiated pathology and BRAF mutation in the MSI group associated with a trend to reduced survival. Chemotherapy and biological therapy received in the MSI v MSS groups was as follows; 5FU 31% v 25%, 5FU/irinotecan 17% v 12%, 5FU/oxaliplatin 52% v 58%, bevacizumab 31% v 42%, anti-EGFR 0 v 4.6%. Conclusions: The patient characteristics of MSI mCRC are in keeping with those previously reported. MSI in this population based mCRC registry is not associated with a favorable outcome as seen in earlier stage disease compared to patients with MSS disease. The trend to poorer outcomes may support routine testing and potentially an alternate treatment pathway, which may include PD-1 inhibitors.[Table: see text]

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Matching for 12 HLA Alleles Is Associated with a Significantly Superior Survival Due to a Lower Mortality in Recipients of Unrelated Donor Haematopoietic Cell Transplants for Early but Not Late Stage Leukaemia.

Blood ◽

10.1182/blood.v110.11.3056.3056 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3056-3056

Author(s):

B.E. Shaw ◽

N.P. Mayor ◽

A.-M. Little ◽

Nigel H. Russell ◽

A. Pagliuca ◽

...

Keyword(s):

Late Stage ◽

Early Stage ◽

Disease Stage ◽

Unrelated Donor ◽

Disease Relapse ◽

Early Stage Disease ◽

Hla Alleles ◽

Graft Versus Host ◽

Multiple Loci ◽

Stage Disease

Abstract Recipient/donor HLA matching is an important determinant of outcome in transplantation using volunteer unrelated donor (VUD). The degree of matching remains controversial. Some data suggest that disease stage is an important factor to consider when assessing the need for a well-matched donor. We analysed the impact of matching for 12 HLA alleles at six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) in a cohort of 458 patients receiving VUD transplants for leukaemia (142 CML, 170 AML, 146 ALL). Of the pairs, 84 were matched for 12/12 alleles, 250 and 124 were mismatched for one locus or more than one locus respectively (graft versus host vector). Most single locus mismatches were at DPB1 (218/250, 87%). In multiply mismatched pairs the loci were: DPB1 plus one other locus (81), 2 other loci excluding DPB1 (10) and more than 2 loci (33). Patients receiving 12/12 matched grafts had a significantly better survival than those who had mismatched grafts (7 years: 45% vs 30%, p=0.022) and those matched for 10/10 alleles (p=0.050). The outcome was not significantly different dependent on whether the mismatch was at single or multiple loci, nor whether the single mismatch was at DPB1 compared to any other HLA locus. Disease stage was a significant determinant of outcome, with patients transplanted in early stage disease (defined as CR1 or CP1, N=222) having a superior outcome to those with late stage disease (N=236) (7 year: 42% vs 28%; p=0.002) In patients with early stage disease, the survival was significantly better if 12/12 matched compared to the mismatched group (7 years: 62% vs 36%; p=0.005). Other factors associated with a significantly improved survival in this cohort were: patient age below the median (32 years), patient CMV seronegativity and CML (rather than acute leukaemia). In multivariate analysis, pairs matched for less than 12/12 HLA alleles (HR=1.8; CI 1.0–3.0; p=0.034) and acute leukaemia (HR=1.8; CI 1.2–2.6; p=0.003) had a significantly worse survival. The reason for the inferior outcome was a significantly worse transplant related mortality (TRM) in the mismatched pairs (p=0.006). This was 16%, 32% and 48% at 100 days, 1 and 7 years in the mismatched group, compared to 9%, 13% and 21% in the matched group. While the incidence of acute graft versus host disease (GvHD) overall was not increased in the mismatched group, the incidence of grade III/IV GvHD was higher (12/12 match = 0%, single locus mismatch = 2%, multiple loci=13%; p=0.002) and this was associated with a higher TRM (p=0.002). There was no significant impact of mismatching on chronic GvHD or disease relapse. Unlike these data, in the late disease stage cohort there was no effect of 12/12 matching status on survival (7 years: 25% vs 28%, NS) or TRM. However, there was an increase in GvHD in HLA mismatched pairs (acute, p=0.012; chronic, p=0.015) and the presence of cGvHD was protective against disease relapse (p=0.044). These data suggest that in patients transplanted at an early disease stage, matching for 12 HLA alleles is important to improve survival. In later stage disease the presence of an HLA mismatch may increase the incidence of GvHD and consequently of the graft versus leukaemia effect and hence be tolerated overall.

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