Page 1381 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 75 Hodgkin Lymphoma 1227

them ineligible for enrollment. Data therefore are not necessarily considered sufficient to allow appropriate ongoing management
representative of the general elderly population. decisions, at least until more comprehensive imaging can be com-
30a
In 2005 Engert and colleagues from the GHSG published the pleted following delivery.
results of a comprehensive retrospective analysis of 4251 patients with Consensus regarding the optimal treatment for pregnant patients
HL showing that acute treatment-related toxicity was higher in older with HL varies. The risk of spontaneous abortion and congenital
patients compared with those under the age of 60 years. In addition, malformations secondary to cytotoxic treatments and/or RT is known
elderly patients with HL had a worse outcome with respect to FFTF to be highest in the first trimester. Although risk decreases as preg-
(60% vs. 80%) and OS (65% vs. 90%), which was attributed to both nancy continues, the exact extent of risk during this period has not
increased mortality during treatment as well as the fact that signifi- been clearly established and long-term complications are unknown.
cantly fewer elderly patients were able to tolerate the intended full This is largely caused by the lack of data that exists as a result of small
dose of therapy (75% vs. 91%). patient numbers. Thus whether chemotherapy should be started or
It is recommended that elderly patients without significant comor- not during pregnancy requires cautious evaluation of the risks to the
bidity and with a good performance status should be treated accord- unborn fetus versus the risks to maternal survival as a result of
ing to the current standard of care for younger individuals, on a postponing treatment. Low-risk, asymptomatic patients may be
risk-adapted basis, according to stage, with curative intent. Treatment- monitored closely, with treatment being delayed until either the end
related toxicity and mortality may, however, occur more frequently. of the first trimester or until delivery if diagnosis occurs later on
In 2005 a prospective randomized trial (H9-elderly), again conducted during the pregnancy. For patients with bulky or symptomatic disease
by the GHSG, compared standard-dose BEACOPP with COPP- that requires treatment, however, single agent anthracyclines or vinca-
ABVD in patients with newly diagnosed advanced HL. Disease- alkaloids are deemed acceptable first choices, escalating to combined
specific FFTF at 5 years was superior with standard-dose BEACOPP chemotherapy, usually with ABVD, following delivery or during the
(74% vs. 55%, p = .13), but survival was not significantly different second or third trimester if there is evidence of progressive disease.
between the two treatment groups because of a higher rate of In this latter subgroup of patients, however, the option of therapeutic
treatment-related mortality in the more intensive BEACOPP regimen abortion should be discussed with the patient and family to ensure
compared with COPP-ABVD (21% vs. 8%). BEACOPP is therefore all decisions made are informed. Traditionally, RT has not been
not recommended for elderly patients. More recently, in 2013, the advised during pregnancy; however, advancing techniques in this area
North American intergroup reported results from the E2496 ran- have led to reduced fetal risk and, as such, it may be considered for
domized trial investigating the efficacy and tolerability of ABVD and selected individuals.
another combination, Stanford V (adriamycin, vinblastine, vincris-
tine, bleomycin, nitrogen mustard, etoposide, prednisolone), in
advanced-stage HL patients aged ≥60 years. Toxicities were compa- Hodgkin Lymphoma in Patients With HIV Infection
rable between the two age groups except for bleomycin lung toxicity
which occurred more frequently in the elderly population receiving The incidence of HL is approximately 10-fold higher among HIV-
ABVD. Overall treatment-related mortality was 9% among older HL positive individuals compared with those who are HIV-negative, and
patients versus 0.3% in those less than 60 years old (p < .001). HL remains the most common non-AIDS defining malignancy. The
Outcome was significantly poorer in the elderly population with vast majority of cases are associated with concurrent EBV infection,
respect to 5-year failure-free survival and 5-year OS (5-year FFS 48% implicating a causative role for EBV in the pathogenesis HL in
vs. 74%, p < .002; OS 58% vs. 90%, p < .0001), although there was HIV-positive patients.
no significant difference in time-to-progression (TTP) (5-year TTP HL occurring in HIV-infected patients typically presents with
68% vs. 78%). more advanced disease, often with extranodal involvement and the
For elderly patients with poorer performance status, either caused presence of B symptoms. In contrast to HL presenting in HIV-
by frailty or the presence of significant comorbidity, standard chemo- negative patients, the mixed cellularity histologic subtype tends to
therapy is not usually considered appropriate. Alternative, reduced predominate in this group.
intensity regimens such as VEPEMB (vinblastine, cyclophosphamide, In the past, before the arrival of highly active antiretroviral therapy
procarbazine, prednisone, etoposide, mitoxantrone, and bleomycin) (HAART), the treatment of HIV-associated HL was challenging,
and, more recently, PVAG (prednisone, vinblastine, doxorubicin, particularly in view of the immunosuppressed state. Less intense
gemcitabine) may be considered, although clear recommendations combination chemotherapy regimens were attempted, but response
have not been established because of a lack of randomized data in was often suboptimal and overall prognosis was poor.
this patient population. For relapsed disease, oral-based palliative Since the widespread use of HAART, however, the treatment
chemotherapy with lomustine (CCNU) has been shown to prolong of patients with HIV-associated HL has evolved and the outcome
disease control in some cases. The potential role of less-toxic novel of these patients has significantly improved. Interestingly, despite
targeted therapies, such as BV, is also under current evaluation for improved outcome, the incidence of HL in HIV-positive patients has
the treatment of elderly patients with HL. increased in the post-HAART era when compared with the start of
the HIV epidemic. It has been postulated that improved CD4 counts,
as a direct result of antiretroviral therapy, have allowed the restoration
Hodgkin Lymphoma During Pregnancy of a more competent immune microenvironment in which newly-
+
populating CD4 T cells are able to support underlying mechanisms
Given that the early incidence peak of HL coincides with childbear- of tumor development. To reinforce this, a pathologic shift has also
ing age its management during pregnancy should assume special been observed following the advent of HAART therapy, with the
consideration. Lymphoma is the fourth commonest malignancy nodular-sclerosing subtype of HL now appearing more frequently
presenting in pregnancy and, of these, HL occurs most frequently. among HIV-positive patients, mirroring the histologic distribution of
The diagnosis of HL during pregnancy matches that of the back- cHL usually seen among the HIV-negative background population.
ground population; lymph node biopsy can be performed safely This concept has important implications when considering effec-
either under local or general anesthetic. Clearly, however, traditional tive treatment for these patients. The enhanced immune environment
staging methods for patients with newly diagnosed HL who are following HAART has allowed more intensive regimens to be tested,
pregnant need to be adapted. To avoid the risks associated with radia- and to good effect. As such, the current recommendation is to treat
tion exposure to the fetus, radiologic evaluation via chest x-ray with newly diagnosed cases of HL in HIV-infected patients with curative
abdominal shielding, abdominal ultrasound, or magnetic resonance intent, using the same treatment approaches that have been adopted
imaging, is recommended rather than CT or PET. Routine blood as standard of care for those without HIV infection. With modern
work and bone marrow biopsy are also indicated, as per standard HIV management, the OS of patients with HIV-associated HL is
practice. This modified approach to staging during pregnancy is similar to that of the background, HIV-negative, population.