Lym­phoma is can­cer of lym­pho­cytes, the cells that are part of human immune sys­tem. The dis­ease was first described in 1832 and can start any­where lym­pho­cytes are found (lymph nodes, spleen, bone mar­row, or diges­tive tracts). Two types are rec­og­nized; Hodgkin lym­phoma (HL) and non-Hodgkin lym­phoma (NHL). The Amer­i­can Can­cer soci­ety esti­mates that approx­i­mately 3800 women and 4600 men will be diag­nosed with HL in 2010. The major­ity of those diag­nosed with HL are chil­dren and young adults (age 15 to 40 years). Mod­ern treat­ment car­ries  high sur­vival rates. (>80%). HD, how­ever, by virtue of the dis­ease itself or its treat­ment poses con­sid­er­able risk to fer­til­ity in women and men, espe­cially if it recurs after treatment.

When HD is sus­pected usu­ally because of enlarged lymph nodes or other symp­toms such as a fever, weight loss or night sweat­ing , a biopsy of lymph nodes is required for the diag­no­sis. Biopsy require spe­cial stains (CD15, CD 30) for pro­teins on the sur­face of the char­ac­ter­is­tic cell. Once con­firmed cer­tain imag­ing stud­ies  (espe­cially PET scan) to detect the extent of the dis­ease. Find more infor­ma­tion about the dis­ease and its treat­ment here.

Chemother­apy for Hodgkin Lym­phoma; com­bi­na­tion chemother­apy is used either ABVD, BEACOPP or MOPP-ABV. Each of the let­ters rep­re­sent one med­ica­tion. The com­bi­na­tion of drugs is used for sev­eral cycles usu­ally 3 to 6. This is the prin­ci­ple treat­ment for HL.

Radi­a­tion ther­apy using exter­nal beam is some­times com­bined with chemother­apy. Radi­a­tion is usu­ally local­ized to the area of the body that har­bors enlarged lymph nodes.

Hematopoi­etic stem cell trans­plan­ta­tion (HSCT). This treat­ment is used for resis­tant HL or HL that recurred after suc­cess­ful treat­ment in the past (relapse). This treat­ment requires 1. very high dose of chemother­apy  and  pos­si­bly total body radi­a­tion then 2. trans­plan­ta­tion of the mother cells of the bone mar­row that pro­duce our blood cells. The sources of these cells could be the per­son him­self (autol­o­gous) a donor per­son (allogenic).

Effects of Hodgkin Lym­phoma and treat­ment on future Fer­til­ity. It has been shawn that men and women attempt­ing con­cep­tion after treat­ment for HL had lower chances of becom­ing preg­nant than gen­eral pop­u­la­tion (Ais­ner 1993).

Men: There is evi­dence to sug­gest that HL itself can affect sperm pro­duc­tion in 50 to 70% of boys and men, prob­a­bly due to dis­tur­bance of the immune cells. Chemother­apy also can be harm­ful to sperm pro­duc­tion. Alky­lat­ing agents espe­cially cyclophos­phamide can cause pro­longed or per­ma­nent azosper­mia (no sperm pro­duc­tion). The other agents may have a reversible effect with some prospect to recov­ery after months to years. The final effect of chemother­apy is dif­fi­cult to pre­dict and is related to the type of reg­i­men and doses used. For exam­ple the old MOPP reg­i­men for 6 or more cycles result in very high rate of azes­per­mia while the newer ABVD reg­i­men usu­ally causes reversible azospermia.

HSCT entails the use of high dose of alky­lat­ing agents and some­times radi­a­tion. It com­monly result in pro­longed azosper­mia. HL or its treat­ment may also affect sperm qual­ity (sperm shape and motil­ity) in addi­tion to con­cen­tra­tion. Sup­pres­sion of sperm pro­duc­tion in the testes using a group of med­ica­tion called gonadotropin releas­ing hor­mone ago­nists (GnRHa) has been sug­gested but there is no proof that they pro­tect the gonads from the effects of treat­ment in men and women. The testes should be sheilded from the radi­a­tion feild when­ever possible.

Women: Chemother­apy for HL can result in reduc­tion of ovar­ian reserve and may reduce future fer­til­ity depend­ing on the med­ica­tion used, dose, fre­quency, inten­sity, age and asso­ci­ated radi­a­tion treat­ment. Mul­ti­ple stud­ies sug­gested that the risk of loss of fer­til­ity is related to 1. Age > 30 years (or > 25years with hifg dose ther­apy) 2. Type of chemother­apy.  MOPP was asso­ci­ated with loss of fer­til­ity than ABVD and BEACOPP. 3. Dose and fre­quency of chemother­apy. Dose esca­la­tion BEACOPP used in more advanced HL was asso­ci­ated more with ovar­ian fail­ure. 4. Expo­sure of the ovaries to radi­a­tion. In a large study about 20% of women expe­ri­enced menopause. In another study about 40% of women were able to con­ceive after treat­ment. In gen­eral pub­lished lit­er­a­ture is not accu­rate in report­ing fer­til­ity poten­tial becaus they used menses as as their end point. Resump­tion of menses after chemother­apy does not accu­rately reflect fer­til­ity poten­tial. The high dose of chemother­apy used prior to HSCT is asso­ci­ated with ovar­ian fail­ure in the vast major­ity of women and girls.

Options for preser­va­tion of fer­til­ity in men. 1. Sperm cry­op­reser­va­tion: This is a widely avail­able and safe option in adults. One or mul­ti­ple sperm sam­ples are obtained and frozen for later use. After remis­sion the sam­ple is thawed and used for intrauter­ine insem­i­na­tion or in vitro fer­til­iza­tion. If IVF is used a sin­gle sperm is injected directly into a part­ner oocyte (ICSI) and the rest of the sperm is refrozen. ICSI is a very pow­er­ful tool that can com­pen­sate for lower qual­ity sperm encoun­tered in men with HL. In pre­pu­ber­tal boys, sperm may be found in the ejac­u­late as early as 12 years. Ask­ing pre­pu­ber­tal boys to pro­duce a sperm sam­ple may carry some eth­i­cal con­sid­er­a­tion. The major­ity of can­cer patients are inter­ested in know­ing their option about preser­va­tion of genetic par­ent­hood in the future. In spite of that, only about one quar­ter freeze their sperm, mainly because of lack of infor­ma­tion about sperm freez­ing (Schover at al 2002). A sur­vey of over 700 oncol­o­gists indi­cated that less than half offer this option to their patients diag­nosed with can­cer. 2. Sur­gi­cal sperm retieval (TESE). Tes­tic­u­lar sperm extrac­tion is a sur­gi­cal pro­ce­dure where a small amount of tis­sue is har­vested directly from the testes to obtain sperm. Its used in men with azosper­mia before start­ing treat­ment. The spec­i­men is frozen for future use with IVF-ICSI. This is a com­mon pro­ce­dure in adults and has been reported in pre­pu­ber­tal boys. 3. Tes­tic­u­lar stem cell freez­ing; either within tes­tic­u­lar biopsy or sep­a­rated cells. This is an exper­i­men­tal method with no reported human preg­nancy. It is con­sid­ered for pre­pu­ber­tal boys. The cells or tis­sue is later trans­planted back for sperm production.

Options for preser­va­tion of fer­til­ity in women. 1. Embryo freez­ing. This tech­nol­ogy is widely avail­able and suit­able for women with a part­ner  (or accept­ing donor sperm) and treat­ment can be delayed for 3 weeks. It require stim­u­la­tion of the ovaries and egg retrieval (an out­pa­tient pro­ce­dure under seda­tion). Embryos can be frozen for a long time and trans­ferred after remis­sion when fer­til­ity is desired. 2. Egg freez­ing. Used in women with no part­ner and declin­ing the use of donor sperm. It also require ovar­ian stim­u­la­tion and a treat­ment delay for 3 weeks. Its gen­er­ally less suc­cess­ful than embryo freez­ing, although the use of vit­ri­fi­ca­tion method can yield com­pa­ra­ble results to embryo freez­ing. 3. Ovar­ian tis­sue freez­ing. This method is exper­i­men­tal. Its used in pre­pu­ber­tal girls or in women that need to start treat­ment urgently and do not have the time to undergo ovar­ian stim­u­la­tion. Its also con­sid­ered in women or girls before under­go­ing HSCT since it is asso­ci­ated with very high rate of ovar­ian fail­ure. One ovary is har­vested usu­ally using min­i­mally access surgery (laparoscopy). Patient is diacharged the same day and can start treat­ment imme­di­ately. The ovary is processed so that the outer part (2mm thin) is iso­lated and frozen. The inner  part of the ovary (does not bear eggs) is sub­mit­ted for patho­log­i­cal exam­i­na­tion. After remis­sion the ovary is trans­planted back in the abdomen or under the skin.

Women and men diag­nosed with Hodgkin Lym­phoma expe­ri­ence  high chance for cure. Coun­sel­ing about fer­til­ity issues before treat­ment can enable them to pre­serve their sperm, eggs or embryos for future use after treat­ment.