ABSTRACT
Background: Platinum-based therapy (PBT) can be limited by gastrointestinal adverse events, particularly PBT-related colitis and diarrhea (PCD). We studied clinical features, treatments, and outcomes of PCD. Methods: This was a retrospective study of cancer patients who received PBT and colonoscopic evaluation for PCD symptoms from 2009 to 2018. Results: Of 36,595 patients who received PBT, 86 (0.2%) met inclusion criteria. Median time from PBT initiation to PCD was 66 days. Regarding PBT type, 47% of the patients received carboplatin, 31% cisplatin, and 22% oxaliplatin. Median duration of PCD symptoms was 20 days. Colonoscopy revealed mucosal ulceration in 34% of the patients and nonulcerative inflammation in 33%. Half of the cohort needed hospitalization for PCD (49%). The majority received treatment for PCD (59%): immunosuppressive therapy in 21%, antibiotics in 27%, antimotility agents in 22%, and intravenous fluids in 51%. Eight patients (9%) were admitted to the intensive care unit for PCD management. Six patients (7%) experienced colonic perforation that required surgical intervention; two of them had gastrointestinal tumors. Physicians restarted PBT in 37 (43%) patients; 8 (22%) of them had PCD recurrence that was managed expectantly. Colonic perforation occurred more frequently with use of oxaliplatin and cisplatin than carboplatin (P=0.05). The median duration of PCD symptoms was longer in patients receiving carboplatin or cisplatin than in those receiving oxaliplatin (P=0.182). Conclusions: PCD is rare, but in a small subset of patients, it can lead to serious complications. Treatment of PCD is mainly supportive, but immunosuppressive therapy may be required.
ABSTRACT
We previously reported that RO(+) expression correlated with increased mutation, activation, and selection among human germinal center (GC) B cells. Here, we subdivided human tonsillar B cells, including IgD(-)CD38(+) GC B cells, into different fractions based on RB expression. Although each subset contained RB(+) cells, when used as an intrasubset marker, differential RB expression effectively discriminated between phenotypically distinct cells. For example, RB(+) GC B cells were enriched for activated cells with lower AID expression. RB inversely correlated with mutation frequency, demonstrating a key difference between RB- and RO-expressing GC B cells. Reduced RB expression during the transition from pre-GC (IgM(+)IgD(+)CD38(+)CD27(-)) to GCB cells was followed by a dramatic increase during the GC-to-plasmablast (IgD(-)CD38(++)CD27(+)) and memory (IgD(-)CD38(-)CD27(+)) transition. Interestingly, RB(+) GC B cells showed increased signs of terminal differentiation toward CD27(+) post-GC early plasmablast (increased CD38 and RO) or early memory (decreased CD38 and RO) B cells. We propose that as in T cells, differential RB expression directly correlates with development- and function-based transitions in tonsillar B cells. Application of this RB:RO system should advance our understanding of normal B-cell development and facilitate the isolation of more discrete B-cell populations with potentially different propensities in disease pathogenesis.