Allogeneic haematopoietic cell transplantation (HCT) is often associated with poor oral intake due to painful mucositis and gastrointestinal sequalae that occur following a preparative regimen of ...intensive chemotherapy and/or total body radiation. Although attractive to assume that optimal nutrition improves HCT outcomes, there are limited data to support this. It is also unclear whether artificial nutrition support should be provided as enteral tube feeding or parenteral nutrition (PN).
We analysed day-100 non-relapse mortality (NRM), incidence of acute graft-versus-host disease (GvHD), acute gastrointestinal GvHD, 5-year survival and GvHD-free/relapse-free survival (GRFS) according to both route and adequacy of nutritional intake prior to neutrophil engraftment, together with other known prognostic factors, in a retrospective cohort of 484 patients who underwent allogeneic HCT for haematologic malignancy between 2000 and 2014.
Multivariate analyses showed increased NRM with inadequate nutrition (hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.2–7.2) and adequate PN (HR 2.9; 95% CI 1.6–5.4) compared to adequate enteral nutrition (EN) both P < .001. There were increased incidences of gastrointestinal GvHD of any stage and all GvHD ≥ grade 2 in patients who received PN (odds ratio (OR) 2.0; 95% CI 1.2–3.3; P = .006, and OR 1.8; 95% CI 1.1–3.0; P = .018, respectively), compared to adequate EN. Patients who received adequate PN and inadequate nutrition also had reduced probabilities of survival and GRFS at 5 years.
Adequate EN during the early transplantation course is associated with reduced NRM, improved survival and GRFS at 5 years. Furthermore, adequate EN is associated with lower incidence of overall and gut acute GvHD than PN, perhaps because of its ability to maintain mucosal integrity, modulate the immune response to intensive chemo/radiotherapy and support the gastrointestinal tract environment, including gut microflora.
Summary
Mesenchymal stromal cells (MSCs) have been successfully used for the treatment of steroid‐resistant graft‐versus‐host‐disease (GvHD). However, the lack of early predictors of clinical ...responses impacts on the time at which to add further treatment and consequently the design of informative clinical trials. Here, we present the UK experience of one of the largest cohorts of GvHD patients undergoing MSC infusions so far reported. We show that clinical responses assessed as early as 1 week after MSC infusion predict patients’ overall survival. In our cohort, cell dose, patients’ age and type of organ involvement are crucial factors associated with clinical responses.
The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to ...multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70%
36%
= 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0%
46%,
= 0.045) or experienced fever (0.29
0.11 days,
= 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients
11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4%
61.9% respectively,
=0.012), and higher non relapse mortality (NRM; 60.2%
16.7% respectively,
=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70%
43.4%,
=0.14) or NRM (12.5%
31.2% respectively,
=0.24) between the FMT-MDRO group and their paired non-MDRO cohort. Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by pre-HCT FMT, even in the absence of intestinal MDRO decolonization. Further work is needed to explore this observed benefit.
Outstanding results have been obtained in the treatment of chronic myeloid leukemia (CML) with first-line imatinib therapy. However, approximately 35% of patients will not obtain long-term benefit ...with this approach. Allogeneic hematopoietic stem cell transplantation (HCT) is a valuable second- and third-line therapy for appropriately selected patients. To identify useful prognostic indicators of transplantation outcome in postimatinib therapeutic interventions, we investigated the role of the HCT comorbidity index (HCT-CI) together with levels of C-reactive protein (CRP) before HCT in 271 patients who underwent myeloablative HCT for CML in first chronic phase. Multivariate analysis showed both an HCT-CI score higher than 0 and CRP levels higher than 9 mg/L independently predict inferior survival and increased nonrelapse mortality at 100 days after HCT. CML patients without comorbidities (HCT-CI score 0) with normal CRP levels (0-9 mg/L) may therefore be candidates for early allogeneic HCT after failing imatinib.
The reverse transcriptase–polymerase chain reaction (RT-PCR) has become widely used for monitoring minimal residual disease after allogeneic stem cell transplantation (SCT) for chronic myeloid ...leukemia (CML). However, most of these studies were performed using qualitative RT-PCR, and the interpretation of the results obtained has been conflicting. The correlation of a quantitative RT-PCR test performed early after SCT (at 3 to 5 months) and long-term outcome of CML patients surviving for more than 6 months was studied. Between January 1991 and June 1999, data from 138 CML patients who received allografts were evaluated. Early RT-PCR results were classified as (1) negative if there were no BCR-ABLtranscripts detected (n = 61), (2) positive at low level if the total number of BCR-ABL transcripts was less than 100 per μg RNA and/or the BCR-ABL/ABL ratio was less than 0.02% (n = 14), or (3) positive at high level if transcript levels exceeded the thresholds defined above (n = 63). Three years after SCT the cumulative incidence of relapse was 16.7%, 42.9%, and 86.4%, respectively (P = .0001). The relationship betweenBCR-ABL transcript level and probability of relapse was apparent whether patients had received sibling or unrelated donor SCT and also whether or not the transplantation was T cell depleted. The results suggest that quantitative RT-PCR performed early after SCT is useful for predicting outcome and may help to define the need for further treatment.
Abstract The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created ...controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure LRF cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval CI, 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk RR, 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P <. 001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.
We analyzed factors having an impact on response to treatment and survival in 78 consecutive patients with chronic myeloid leukemia (CML) in blastic transformation (BT) referred to the Hammersmith ...Hospital from January 1995 to December 2000. BT was defined as the presence of at least 30% blasts in blood or marrow or extramedullary blastic deposits. Immunophenotyping of blasts showed 57 myeloid, 19 lymphoid, and 2 biphenotypic. The median age of the patients was 39.1 years (range, 11.3-73.4 years), with 55 males and 23 females. The median survival for all patients after onset of BT was 8.2 months (95% CI, 6.4-10). Patients in lymphoid BT survived longer than those in myeloid BT (median, 11.2 months versus 6.9 months, P = .052). Initial treatment varied; 41 patients received cytotoxic drugs, 8 underwent allogeneic or autologous transplantation procedures, 21 received STI571 (imatinib mesylate, Gleevec), 1 received radiotherapy, and 7 received no therapy. Of the 25 (32%) patients who achieved a “second chronic phase” with first therapy, 6 of 21 (29%) were treated with STI571 and 19 of 50 (38%) were treated with chemotherapy, transplantation, or radiotherapy. Patients who achieved a second chronic phase survived longer than those who did not (median time from onset of BT 12.0 months versus 6.3 months, P = .0004). In multivariate analysis the finding of more than 50% blast cells in the blood and the presence of cytogenetic progression were independent adverse prognostic variables for survival. We conclude that survival after onset of BT has improved in recent years but is still unsatisfactory. We speculate that the combined use of STI571 with cytotoxic drugs may offer additional benefit.
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