Page 1661 - Williams Hematology ( PDFDrive )

1636 Part XI: Malignant Lymphoid Diseases Chapter 98: Diffuse Large B-Cell Lymphoma and Related Diseases 1637

of rituximab improves clinical outcomes. 131,132 One study analyzed and more aggressive monoclonal PTLD are less likely to respond. Rit-
143
106 patients who received chemotherapy either with rituximab (R-che- uximab has shown promising results in the treatment of CD20+ PTLD.
132
motherapy, n = 49) or without rituximab (chemotherapy, n = 57). In a multicenter prospective trial, 43 patients with previously untreated
The CR rate was 82 percent for patients in the R-chemotherapy group B-cell PTLD who failed to respond to tapering of immunosuppression,
2 144
compared to 51 percent in the chemotherapy-alone group (p = 0.001). were treated with 4 weekly injections of rituximab at 375 mg/m . The
PFS and OS rates 2 years after diagnosis were 56 and 66 percent, respec- overall response rate was 44 percent, with an OS of 86 per cent after
tively, in the R-chemotherapy group, compared with 27 and 46 percent 80 days and 67 percent after 1 year. The only baseline factor predicting
for patients in the chemotherapy-alone group (p = 0.001 for PFS and p = response at day 80 was a normal level of serum LDH. A retrospective
0.01 for OS). More intensive chemotherapy including high-dose metho- study evaluated the efficacy and safety of chemotherapy salvage ther-
trexate and/or high-dose cytarabine are recommended for patients with apies in adult recipients of solid-organ transplants with a second pro-
145
CNS involvement (e.g., R-CHOP with high-dose methotrexate). Many gression of PTLD after initial therapy with rituximab. CHOP therapy
authorities believe that CNS prophylaxis is warranted even in cases of achieved a favorable overall response rate of 70 percent in this setting,
intravascular large cell lymphoma without demonstrable CNS disease at indicating that PTLD generally remains chemotherapy-sensitive after
diagnosis, because of the high rate of CNS relapse. progression following initial therapy with rituximab.
A prospective trial evaluated a stepwise treatment approach
POSTTRANSPLANT LYMPHOPROLIFERATIVE beginning with reduction of immunosuppression, then interferon-α,
and finally chemotherapy with ProMACE-CytaBOM plus granulo-
DISORDERS cyte-monocyte colony-stimulating factor. Sixteen eligible patients
146
Definition began treatment with reduced immunosuppression. The response rate
Posttransplantation lymphoproliferative disorders (PTLD) result from to reduced immunosuppression was zero of 16 CR and one of 16 PR
lymphoid or plasmacytic proliferations that develop in the setting of (6 percent). Six of the 16 patients (38 percent) had documented rejec-
solid-organ or marrow transplantation. Although PTLD represents an tion of the transplanted organ during the period of reduced immu-
uncommon complication in transplant patients, it is a significant cause nosuppression. Eight of the 16 patients had documented progressive
of morbidity and mortality. 133 disease during the period of reduced immunosuppression. Thirteen
patients underwent treatment with interferon, with two patients achiev-
Epidemiology ing CRs (15 percent) and two achieving PRs (15 percent). Seven eligible
The incidence of PTLD is approximately 1 to 2 percent in solid-organ patients proceeded to ProMACE-CytaBOM chemotherapy with five
transplant recipients, which is 30 to 50 times higher than the incidence (67 percent) attaining CR. Four of the five CRs experienced remission
of lymphoproliferative diseases in the immunocompetent general pop- durations of more than 2 years. The median survival for the treatment
ulation. There is a clear association between PTLD and the type of cohort as a whole was 19 months, with a range of 5 days to 60+ months.
134
organ transplanted. Among the most commonly transplanted solid Overall survival was 50 percent at 2 years, 44 percent at 4 years, and 24
organs, heart, lung, and intestinal transplantation have the highest inci- percent at 8 years.
135
dences of PTLD, with the highest risk occurring in the first year after The following sequence is currently recommended for PTLD: The
transplantation. The incidence of PTLD after blood or marrow trans- first intervention should be reduction in immunosuppression, followed
plantation is lower than after solid-organ transplantation and ranges by four weekly cycles of rituximab if reduction of the immunosuppres-
from 0.5 to 1.0 percent in reported series. sion by itself is ineffective. If PTLD does not regress with these mea-
sures, then six cycles of R-CHOP are recommended.
Pathogenesis
The major risk factors that have been identified for the development of
PTLD include EBV-positive serology pretransplantation, type of organ T-CELL–HISTIOCYTE-RICH LARGE B-CELL
transplanted, and intensity of immunosuppressive regimen used. 136–138 LYMPHOMA
The onset of posttransplantation lymphoma in most patients is related Definition
to B-cell proliferation induced by infection with EBV in the setting of T-cell–histiocyte-rich large B-cell lymphoma is characterized by efface-
chronic immunosuppression. The genome of the virus can be detected ment of the architecture of the lymph node by a lymphohistiocytic
139
in the cells of the majority of cases. However, in approximately 20 to infiltrate with a diffuse or vaguely nodular growth pattern. 2,147 There are
30 percent of cases the virus is undetectable in involved tissues. a limited number of large atypical B cells occurring singly or in small
140
Involvement of the lymph nodes, gastrointestinal tract, lungs, and clusters with a predominant background infiltrate composed of T cells
liver are common with all types of allografts. The majority of PTLDs and histiocytes, the latter usually of the nonepithelioid type.
in solid-organ transplant recipients are of host origin. In contrast, the
majority of PTLDs in hematopoietic stem cell allografts are of donor
origin. Involvement of the grafted organ occurs in approximately 30 per- Epidemiology
cent of patients and may lead to organ damage and fatal complications. 141 T-cell–histiocyte-rich large B-cell lymphoma accounts for less than
5 percent of all cases of DLBCL and occurs at a younger age on average.
Therapy The median age of onset is in the fourth decade, compared to the sixth
Management of PTLD is not uniform. A wide variety of approaches, decade for DLBCL. 148–151 A male predominance is noted in most series,
including decreasing the dose of immunosuppressive drugs or adminis- in contrast to DLBCL not otherwise specified, which occurs equally in
tering antiviral therapy, interferon, intravenous immunoglobulin, adop- men and women.
tive therapy with EBV-specific cytotoxic T lymphocytes, chemotherapy,
radiation, and rituximab therapy, have been reported. If feasible, reduc- Clinical Features
tion of immunosuppression is the first step in the management of such This variant more often presents with advanced stage disease, B symp-
patients. Many cases of polyclonal PTLD resolve completely with a toms, an elevated LDH, splenic infiltration and multiple extranodal sites
reduction in immunosuppressive therapy. Patients with late PTLD (especially the marrow and liver) compared to standard DLBCL. 148–150,152
142

Kaushansky_chapter 98_p1625-1640.indd 1636 9/18/15 11:42 PM