Pregnancy outcome in patients treated for Hodgkin's disease.

PURPOSE This study attempted to determine the outcome of pregnancies in patients (or their partners) who were successfully treated for Hodgkin's disease and to assess the effect of treatment on the children of the treated parents. MATERIALS AND METHODS A questionnaire was distributed to and personal interviews were conducted with patients who were of reproductive age at the time of treatment with consecutive protocols of radiotherapy, chemotherapy, or both. Those premenopausal patients (or the sexual partners of patients) who attempted to conceive after successful treatment constituted the study population. Fertility assessment was based only on those patients identified as desiring children. RESULTS Among 391 adult patients, 221 patients (104 females and 117 males) of reproductive age were interviewed. Before treatment, 63 of the 221 patients had 135 pregnancies, which resulted in 118 children, 11 spontaneous abortions, five elective abortions, and one stillborn. After treatment, 94 patients (43 females and 51 males) actively attempted conception; 35 females and 25 partners of male patients had 84 pregnancies, which resulted in 68 living children. Among the 84 pregnancies, there were one premature birth at 29 weeks, three spontaneous abortions, 11 elective abortions, and two stillborn: one at 32 weeks and one set of twins. The children have been observed for a median of 11 years (minimum follow up > 4.5 years). Of those patients who desired children, 35 of 43 females became pregnant, whereas only 25 of the 51 partners of male patients became pregnant. At least five male patients with low sperm counts apparently fathered children. CONCLUSIONS This study demonstrates that both men and women have the potential for fertility after treatment regardless of treatment modality. The partners of male patients who were treated with combined modality treatment had a lower frequency of pregnancy than did the female patients who attempted conception and their frequency of pregnancy was also lower than the general population. There was no apparent increase in complications of pregnancy, spontaneous abortions, or congenital abnormalities after treatment compared with pregnancies in this patient group before treatment or with pregnancies in the general population.

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Prognostic factors for positive surgical staging in patients with Hodgkin's disease.

Journal of Clinical Oncology ◽

10.1200/jco.1990.8.2.257 ◽

1990 ◽

Vol 8 (2) ◽

pp. 257-265 ◽

Cited By ~ 89

Author(s):

P Mauch ◽

D Larson ◽

R Osteen ◽

B Silver ◽

B Yeap ◽

...

Keyword(s):

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Surgical Staging ◽

Clinical Staging ◽

Treatment Change ◽

Staging Laparotomy ◽

Abdominal Disease ◽

Study Population ◽

Male Patients ◽

Male Sex

Staging laparotomy was performed as part of the routine recommended diagnostic evaluation following clinical staging (CS) in 692 patients presenting with supradiaphragmatic Hodgkin's disease (HD). Various clinical factors were analyzed by multivariate analysis for prediction of abdominal involvement. Factors that were statistically significant for predicting disease below the diaphragm included CS III-IV disease (P less than .001), B symptoms (P less than .001), mixed cellularity (MC) or lymphocytic depletion (LD) histology (P = .017), number of supradiaphragmatic sites greater than or equal to 2 (P = .001), male sex (P = 0.034) and age greater than or equal to 40 years (P = .004). Separate analyses were performed for various subgroups of CS IA-IIA, CS IB-IIB, CS IIIA-IVA, and CS IIIB-IVB patients. Upstaging was seen in 0% to 55% of CS I-II patients based on subgroup. Male sex, B symptoms, and number of sites above the diaphragm greater than or equal to 2 all independently predicted for positive surgical staging in CS I-II patients. Sixty-four percent of CS I-II patients who were upstaged had extensive abdominal disease by positive lower abdominal nodes or multiple splenic nodules (greater than or equal to 5). Downstaging (to pathological stage [PS] I-II) was seen in 9% to 68% of patients with CS III-IV disease based on subgrouping. Age greater than or equal to 40, MC or LD histology, and B symptoms all independently predicted for positive surgical staging in CS III-IV patients. Downstaging was more frequently seen in CS IIIA-IVA patients (55%) than in patients who were CS III-IVB (22%). Four subgroups of patients who had a low probability (less than 10%) of stage or treatment change following laparotomy were identified. These included CS IA female patients, CS IA male patients with lymphocyte predominance histology or high neck presentations, and patients with CS IIIB-IVB disease and account for 21% of the study population. Staging laparotomy altered the stage and treatment of a significant number of the remaining 79% patients and should continue to be recommended for this group of patients.

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Second cancer risk following Hodgkin's disease: a 20-year follow-up study.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.2.312 ◽

1994 ◽

Vol 12 (2) ◽

pp. 312-325 ◽

Cited By ~ 316

Author(s):

F E van Leeuwen ◽

W J Klokman ◽

A Hagenbeek ◽

R Noyon ◽

A W van den Belt-Dusebout ◽

...

Keyword(s):

Risk Factors ◽

Lung Cancer ◽

General Population ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Significant Risk ◽

Combined Modality Treatment ◽

Increased Risk

PURPOSE To determine risk factors for the development of second primary cancers during long-term follow-up of patients with Hodgkin's disease (HD). PATIENTS AND METHODS We assessed the risk of second cancers (SCs) in 1939 HD patients, who were admitted to the Netherlands Cancer Institute (NKI; Amsterdam) or the Dr Daniel den Hoed Cancer Center (DDHK; Rotterdam) between 1966 and 1986. For 97% of the cohort, we obtained a medical status up to at least January 1989. The median follow-up duration of the patients was 9.2 years; for 17% of the patients, follow-up was longer than 15 years. For more than 98% of all second tumors, the diagnosis was confirmed through a pathology report. RESULTS In all, 146 patients developed a SC, compared with 41.9 cases expected on the basis of incidence rates in the general population (relative risk [RR], 3.5; 95% confidence interval [CI], 2.9 to 4.1). The mean 20-year actuarial risk of all SCs was 20% (95% CI, 17% to 24%). Significantly increased RRs were observed for leukemia (RR, 34.7; 95% CI, 23.6 to 49.3), non-Hodgkin's lymphoma (NHL) (RR, 20.6; 95% CI, 13.1 to 30.9), lung cancer (RR, 3.7; 95% CI, 2.5 to 5.3), all gastrointestinal cancers combined (RR, 2.0; 95% CI, 1.2 to 3.1), all urogenital cancers combined (RR, 2.4; 95% CI, 1.4 to 3.7), melanoma (RR, 4.9; 95% CI, 1.6 to 11.3), and soft tissue sarcoma (RR, 8.8; 95% CI, 1.8 to 25.8). As compared with the general population, the cohort experienced an excess of 63 cancer cases per 10,000 person-years. Cox-model analysis indicated the following as significant risk factors for developing leukemia: first-year treatment with chemotherapy (CT), follow-up treatment with CT, age at diagnosis of HD greater than 40 years, splenectomy, and advanced stage. Patients treated with CT in the 1980s had a substantially lower risk of leukemia than patients treated in the 1970s (10-year actuarial risks of 2.1% and 6.4%, respectively; P = .07). Significant risk factors for NHL were older age, male sex, and combined modality treatment as compared with either modality alone. Risk of lung cancer was strongly related to radiotherapy (RT), while an additional role of CT could not be demonstrated. After more than 15 years of follow-up, women treated with mantle-field irradiation before age 20 years had a greater than forty-fold increased risk of breast cancer (P < .001). CONCLUSION While the long-term consequences of HD treatment as administered in the 1960s and 1970s are still evolving, it is promising that patients who received the new treatment regimens introduced in the 1980s have a much lower leukemia risk than patients treated in earlier years. Beginning 10 years after initial RT, the follow-up program of women who received mantle-field irradiation before age 30 years should routinely include breast palpation and yearly mammography.

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Combined modality treatment with reduced chemotherapy and radiotherapy, and selective splenectomy, in children with Hodgkin’s disease

Malignant Lymphomas and Hodgkin’s Disease: Experimental and Therapeutic Advances ◽

10.1007/978-1-4613-2607-6_65 ◽

1985 ◽

pp. 617-626 ◽

Cited By ~ 6

Author(s):

G. Schellong ◽

S. Strauch ◽

A. K. Waubke ◽

W. Brandeis ◽

J. Pawlowsky ◽

...

Keyword(s):

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Combined Modality Treatment ◽

Combined Modality

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Rapid recovery of spermatogenesis after mitoxantrone, vincristine, vinblastine, and prednisone chemotherapy for Hodgkin's disease.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.12.3488 ◽

1997 ◽

Vol 15 (12) ◽

pp. 3488-3495 ◽

Cited By ~ 50

Author(s):

M L Meistrich ◽

G Wilson ◽

K Mathur ◽

L M Fuller ◽

M A Rodriguez ◽

...

Keyword(s):

Hodgkin's Disease ◽

Male Fertility ◽

Sperm Count ◽

Hodgkin’S Disease ◽

Spermatogenic Cells ◽

Sperm Production ◽

Human Male ◽

Sperm Counts ◽

Abdominal Radiotherapy ◽

Upper Abdominal

PURPOSE Because the effects of mitoxantrone on human male fertility were unknown, we determined prospectively the effects of three courses of mitoxantrone (Novantrone), vincristine (Oncovin), vinblastine, prednisone (NOVP) chemotherapy on the potential for fertility of men with Hodgkin's disease (HD). PATIENTS AND METHODS Semen analyses were performed on 58 patients with stages I-III HD before, during, and after chemotherapy and after the sperm count recovered from the effects of abdominal radiotherapy that was given after chemotherapy. RESULTS Before the initiation of treatment, 84% of the patients were normospermic. Sperm counts declined significantly within 1 month after the start of NOVP chemotherapy. In the month after chemotherapy, 38% of patients were azoospermic, 52% had counts < 1 million/ mL, and 10% had counts between 1 and 3 million/mL. Between 2.6 and 4.5 months after the completion of chemotherapy, sperm counts recovered rapidly to normospermic levels in 63% of patients. In the remaining patients who were followed up for at least 1 year after standard upper abdominal radiotherapy, counts also recovered to normospermic levels. CONCLUSION NOVP chemotherapy, like most other regimens, produced marked temporary effects or spermatogenesis. However, sperm production recovered very rapidly, within 3 to 4 months after the end of NOVP chemotherapy. This pattern was caused by killing differentiating spermatogenic cells, but there was little cytotoxicity or inhibition of stem cells from mitoxantrone or the other drugs. After the combination of NOVP plus abdominal radiotherapy, sperm counts and motility were restored in most patients to pretreatment levels, which were compatible with normal fertility.

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Improved survival in patients with limited stage IIIA Hodgkin's disease treated with combined radiation therapy and chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.12.2567 ◽

1994 ◽

Vol 12 (12) ◽

pp. 2567-2572 ◽

Cited By ~ 7

Author(s):

K C Marcus ◽

L A Kalish ◽

C N Coleman ◽

L N Shulman ◽

D S Rosenthal ◽

...

Keyword(s):

Radiation Therapy ◽

Prognostic Factors ◽

Survival Rate ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Survival Rates ◽

Stage Iii ◽

Combined Modality Treatment ◽

Stage Iiia ◽

Long Term Treatment

PURPOSE Patients with laparotomy-staged (PS) III 1A Hodgkin's disease confined to the upper abdomen are believed to have a favorable prognosis and require less aggressive treatment than patients with more-extensive stage III disease. We evaluated prognostic factors and outcome in 93 patients with PS III 1A Hodgkin's disease treated either with radiation therapy (RT) alone or combined RT and chemotherapy (combined modality treatment [CMT]) to determine the extent of treatment needed in this subgroup of stage IIIA patients. MATERIALS AND METHODS We retrospectively reviewed the freedom from relapse (FFR) rate, sites of recurrence, and survival rate of PS III 1A patients selected to receive extended-field irradiation (MPA, n = 27), total-nodal irradiation (TNI, n = 34), and CMT (n = 32) between 1969 and 1987. CMT consisted of six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy and MPA. Patients treated with MPA were part of a prospective trial designed to reduce treatment to patients with minimal stage III disease with very favorable characteristics. RESULTS Histologic subclass and treatment were the only prognostic factors for FFR and survival rates. Patients with nodular sclerosis or lymphocyte predominance histology had significantly higher FFR and survival rates compared to patients with mixed-cellularity (MC) histology. The 10-year actuarial FFR of PSIII 1A patients treated with MPA was only 39%, versus 55% for TNI (P = .02) and 94% for CMT (v MPA, P < .0001; v TNI, P = .006). The patterns of recurrence in patients who received MPA and TNI were significantly different, with MPA patients relapsing more often in untreated pelvic or inguinal nodes, and TNI patients relapsing more often in extranodal sites with or without nodal sites. The 10-year actuarial overall survival rate for patients treated with CMT was 89% versus 78% for MPA (v CMT, P = .09) and 70% for TNI (v CMT, P = .05). CONCLUSION Patients with PSIII 1A Hodgkin's disease treated with RT have a significantly higher risk of relapse and potentially a poorer survival compared with patients treated with CMT. These findings suggest that CMT should play a greater role in the treatment of this favorable substage of patients. Management with modified chemotherapy and RT in an attempt to reduce long-term treatment-induced complications may be a preferred approach for future trials.

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